Genetics
дополнительные статьи

Genetic Center
Filatov's Child Clinical Hospital © 2001-2004
Vladimir Solonichenko MD, Clinical Geneticist,©
E-mail:

06.24.2004

	REFERENCES - FIRST PUBLICATIONS 1999	ABSTRACTS
1	Achermann Sibylla, Remo Largo, Dieter Kotzot, Mariluce Riegel, Albert Schinzel Short stature, myopia, severe developmental delay, and peculiar facial appearance in two brothers: A new syndrome? Am J Med Genet., 86(5):486-491,1999	We report on 2 brothers with short stature, microcephaly, myopia, retarded osseous maturation, severe developmental delay, and minor anomalies including temporal narrowing, periorbital fullness, full cheeks in infancy, and protruding lower lip. Both brothers and their parents had normal chromosomes. Fluorescence in situ hybridization with probes from all (sub-)telomeric chromosomal regions excluded a structural rearrangement involving telomeric segments. Because the pattern of congenital abnormalities is not like that of any well-known multiple congenital anomaly/mental retardation syndrome, we suggest a previously undescribed syndrome of autosomal recessive or X-linked inheritance.
2	ABDEL-SALAM Ghada M.E., M. BUCSEK and A.E. CZEIZEL. Alopecia Universalis, Cleft Palate and Lip, Hypohydrosis, Hypodontia, Nail Dysplasia and Syndactyly: New Ectodermal Dysplasia Syndrome? Cong. Anom., 39: 37-42, 1999	The 3 year old girl has hypohydrotic ectodermal dysplasia, cleft lip and palate, striking alopecia with total absence of eye brows and body hair (alopecia universalis), epicanthic folds, strabismus, malpositioned small square-shaped teeth with absent one in the upper jaw, small fingers with dysplastic nails and toes, pilonidal sinus, partial syndactyly between the 2nd and 3rd toes, ans slight developmental delay.
3	Abidi F, Hall BD, Cadle RG, Feldman GL, Lubs HA, Ouzts LV, Arena JF, Stevenson RE, Schwartz CE. X-linked mental retardation with variable stature, head circumference, and testicular volume linked to Xq12-q21. Am J Med Genet 1999 Jul;85(3):223-229	Clinical and molecular studies are reported on a family with X-linked mental retardation (XLMR) in which there are eight affected males in three generations. Although the males have somatic manifestations, these are variable and in most cases do not allow clear distinction of affected and unaffected males. Affected males are shorter and have a smaller head circumference. Several also have a sloping forehead (5/8), hearing loss (3/8), cupped ears (2/8), and small testes (4/6). An LOD score of 4.41 with zero recombination was obtained at locus DXS1166 in Xq13.2. This family highlights the difficulty in classifying XLMR conditions as either nonsyndromic or syndromic because of the variable somatic manifestations observed in the affected males.
4	Adachi M, Tachibana K, Asakura Y, Suwa S, Nishimura G. A male patient presenting with major clinical symptoms of glucocorticoid deficiency and skeletal dysplasia, showing a steroid pattern compatible with 17alpha-hydroxylase/17,20-lyase deficiency, but without obvious CYP17 gene mutations. Endocr J 1999 Apr;46(2):285-92	We report the case of a 17-year-old boy with delayed puberty, who presented a complexity of clinical problems. An analysis of steroid hormones led to a diagnosis of 17alpha-hydroxylase/17,20-lyase deficiency (17OHD). Unlike typical cases of 17OHD, however, the patient had pubertal development without medical intervention. In addition, he never exhibited the symptoms of mineralocorticoid excess, showing instead the symptoms of glucocorticoid deficiency, including fatigability, emaciation, and weight-loss induced by minor infection. He also had dysmorphic features, which comprised marfanoid habitus, arachnodactyly and putative craniosynostosis. The combination of these malformations substantially resembled that of Shprintzen-Goldberg syndrome. Direct sequencing of the CYPl7 gene did not reveal any significant aberrations in the exons or exon-intron boundaries. We speculate that the association of partial combined 17OHD with the Shprintzen-Goldberg phenotype in the present patient may result from an aberration of a hitherto unknown gene that controls both steroid hormone synthesis and skeletal development.
5	Ades LC, Davies R, Haan EA, Holman KJ, Watson KC, Sreetharan D, Cao SN, Milewicz DM, Bateman JF, Chiodo AA, Eccles M, McNoe L, Harbord M. Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.Clin Dysmorphol 1999 Oct;8(4):269-76	We describe a 14-year-old male with dissection of the descending aorta, bilateral iris hypoplasia, striae distensae and brachytelephalangy, the latter being most marked in the thumbs. Inguinal herniae and a patent ductus arteriosus were surgically repaired in infancy. The pattern of abnormalities may constitute a previously undescribed syndrome. The proband died suddenly at the age of 17 years.
6	Aftimos S, Winship I. A patient with VACTERL association, amelia and hemifacial microsomia. Clin Dysmorphol 1999 Apr;8(2):135-7	We report on a girl with anal atresia, renal aplasia, vertebral and rib anomalies, amelia and hemifacial microsomia. The patient demonstrates the overlap between the VACTERL association and the oculoauriculovertebral dysplasia. We propose that amelia is a severe manifestation of the limb defects which occur in these developmental dysplasias.
7	Agarwala S, Goswami JK, Mitra DK. Pyloric atresia associated with epidermolysis bullosa, malrotation, and high anorectal malformation with recto-urethral fistula: a report of successful management. Pediatr Surg Int 1999;15(3-4):264-5	Pyloric atresia (PA) is an uncommon anomaly that may be associated with many other congenital anomalies, the commonest of which is junctional epidermolysis bullosa (JEB). Most of the cases of PA associated with JEB (Herlitz syndrome) reported have been fatal. A case of PA associated with JEB, malrotation, and a high anorectal malformation with a rectourethral fistula, which was hitherto undescribed, was successfully managed at our institution.
8	Ahmad Wasim, Maurizio De Fusco, Muhammad Faiyaz ul Haque, Paolo Aridon, Tiziana Sarno, Muhammad Sohail, Sayed ul Haque, Mahmud Ahmad, Andrea Ballabio, Brunella Franco & Giorgio Casari. Linkage mapping of a new syndromic form of X-linked mental retardation, MRXS7, associated with obesity. Eur J Hum Genet., 1999, 7(7):828 - 832	A new syndromic form of X-linked mental retardation associated to obesity, MRXS7, has been localised to Xp11.3-Xq23 in a large Pakistani family. The ten affected males show clinical manifestations of mental retardation, obesity and hypogonadism. The family was genotyped by a set of microsatellite markers spaced at approximately 10 cM intervals on the X chromosome. Linkage to five adjacent microsatellite markers, mapping in the pericentromeric area, was established and a maximum two-point lod score of 3.86 was reached at zero recombination with marker DXS1106. Reduced recombination events around the centromere prevented precise mapping of the gene.
9	al-Gazali LI, Bakalinova D, Aziz S, Anwer O, Shather W, Sztriha L. Hypocalvaria associated with intrauterine growth retardation, facial dysmorphism, congenital heart disease and camptomelia.Clin Dysmorphol 1999, 8(2):129-134	We report an Omani child from an inbred family with a combination of hypocalvaria, intrauterine growth retardation, craniofacial disproportion, partial synostosis of the right coronal suture and a small mandible associated with congenital heart defect and bowing of the limbs. A literature search failed to reveal a similar case.
10	Al-Gazali LI, Sztriha L, Punnose J, Shather W, Nork M. Absent pituitary gland and hypoplasia of the cerebellar vermis associated with partial ophthalmoplegia and postaxial polydactyly: a variant of orofaciodigital syndrome VI or a new syndrome? J Med Genet 1999, 36(2):161-166	We report two sibs with features overlapping those of orofaciodigital syndrome type VI (Varadi syndrome). Both presented at birth with oculomotor abnormalities, dysmorphic facial features, and dysgenesis of the cerebellar vermis. There were minimal oral manifestations (high arched palate) in both of them and one had postaxial polydactyly of both hands and one foot. In addition, there was evidence of aplasia of the pituitary gland on MRI scan in both of them with evidence of hypopituitarism. Both responded well to hormone replacement therapy with improvement in their linear growth and mental ability. These cases may represent a new autosomal recessive midline defect syndrome with features overlapping OFDS VI. Alternatively the features in these children could represent variability within OFDS VI.
11	Amiel Jeanne, Valérie Cormier-Daire, Pierre Journeau, Philippe Mussat, Arnold Munnich, Stanislas Lyonnet. Epiphyseal, vertebral, and ear (EVE) dysplasia: a new syndrome? J Med Genet 1999;36:561-564	We report on the association of epiphyseal, vertebral, and ear dysplasia in two sisters with normal stature and psychomotor development born to distantly related, healthy parents. This distinctive association has not been reported previously and is likely to represent a new condition with an autosomal recessive mode of inheritance. For this syndrome, we propose the acronym EVE standing for epiphyseal, vertebral, and ear dysplasia.
12	Amirlak Iradj, Sharda G Sabnis, Lihadh Al-Gazali, Yousef M Abdulrazzaq. A syndrome of immune complex glomerulonephritis and ophthalmic abnormalities. J Med Genet 1999;36:641-644	Two sibs (one male and one female) suffering from a combination of immune complex glomerulonephritis and various ophthalmologic disorders are presented. The two cases belong to a family in which the parents are not related and seven sibs are affected, three females and a male with the combination, and three males with severe ophthalmological changes and proteinuria. Clinically, case 2 had only ophthalmological manifestations but renal biopsy findings were similar to those of case 1, which could mean that all the others with eye abnormalities also had renal disease. Although there are several reports of combinations of eye and renal disorders, the sibs reported here do not fit into any of the known syndromes.
13	Angelicheva Dora, Ivailo Turnev, Danielle Dye, David Chandler, PK Thomas & Luba Kalaydjieva. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. Eur J Hum Genet., 1999, 7(5):560 - 566	We have identified a novel developmental disorder with complex phenotypic characteristics involving primarily the nervous system, which appears to be common in a specific Gypsy group in Bulgaria. We propose to refer to the syndrome as congenital cataracts facial dysmorphism neuropathy (CCFDN). We have assigned the disease locus to the telomeric region of chromosome 18q. Linkage disequilibrium and highly conserved haplotypes suggest genetic homogeneity and founder effect. CCFDN co-localises with an EST which shows high homology to a conserved Drosophila gene involved in the regulation of nervous system development in vertebrates.
14	Armfield Kim, Retecher Nelson, Herbert A. Lubs, Bernhard Häne, Richard J. Schroer, Fernando Arena, Charles E. Schwartz, Roger E. Stevenson. X-linked mental retardation syndrome with short stature, small hands and feet, seizures, cleft palate, and glaucoma is linked to Xq28. Am J Med Genet 1999, 85(3):236-242	Of the gene-rich regions of the human genome, Xq28 is the most densely mapped. Mutations of genes in this band are responsible for 10 syndromal forms of mental retardation and 5 nonsyndromal forms. Clinical and molecular studies reported here add an additional syndromic form of X-linked mental retardation (XLMR) to this region. The condition comprises short stature, small hands and feet, seizures, cleft palate, and glaucoma. One affected male died at age 19 years in status epilepticus, but others have survived to old age. Carrier females do not have somatic anomalies or mental impairment. The gene is localized to the terminal 8 Mb of Xq28 with markers distal to DXS8011 showing linkage to the disorder with a lod score of 2.11 at zero recombination.
15	Aurora P, and Wallis C.E. Jeune syndrome (asphyxiating thoracic dystrophy) associated with Hirschprung disease. Clin Dysmorph., 1999, 8(4):259-263	No abstract available.
16	Autti T, Muttilainen M, Raininko R, Heiskala H, Puranen J, Hakkinen AM, Tienari P, Santavuori P, Suominen P, Somer M. Extensive cerebral white matter abnormality without clinical symptoms: a new hereditary condition? Ann Neurol 1999, 45(6):801-805	A 30-year-old father and his 2 sons with slight hyperkinesia and mildly dysmorphic features and their close relatives were examined clinically and with computed tomography (CT) and magnetic resonance imaging (MRI). Neurophysiological and biochemical examinations were normal; however, brain MRI of the father and sons revealed extensive cerebral white matter changes. No radiological progression could be detected at a 13-year follow-up examination of the father, and proton magnetic resonance spectroscopy (MRS) of the father at the age of 30 years was normal. MRI findings in the relatives were normal, suggesting an autosomal dominant syndrome due to a new mutation in the father.
17	Balci S, Bostanoglu S, Altinok G, Ozaltin F. Sibs diagnosed prenatally with situs inversus totalis, renal and pancreatic dysplasia, and cysts: A new syndrome? Am J Med Genet., 1999, 82(2):166-169	We describe two sib fetuses with situs inversus, cystic dysplastic kidney and pancreas, bowing of the lower limbs and clavicles, severe intrauterine growth retardation (IUGR), and oligohydramnios. Early prenatal diagnosis of pancreatic and dysplastic renal cysts and situs inversus totalis were made in the 18-week-old fetus. This syndrome differs from that of Ivemark and related syndromes because of the presence of situs inversus totalis and absence of hepatic fibrosis and cysts. The parents were first cousins, and did not have any cysts of kidney, liver, or pancreas detected by ultrasonography.
18	Bartsch Oliver, Annett Wagner, Georg K Hinkel, Petra Krebs, Markus Stumm, Bernhard Schmalenberger, Sabine Bohm, Sevim Balci & Frank Majewski, FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy. European Journal of Human Genetics, 1999, 7, 7, pp 748 - 756	Rubinstein-Taybi syndrome (RTS) is a dominant Mendelian disorder characterised by mental retardation, a typical facies, broad thumbs and short stature. Previous reports indicated that 4-25% of RTS patients have a submicroscopic 16p13.3 deletion of the CBP gene. Using FISH and cosmid probes RT100, RT191 and RT203 we studied 45 RTS patients from Germany, the Czech Republic, Austria and Turkey and found four deletions (8.9%, pooled data including other studies: 11%). All deletions were interstitial; three spanned the CBP gene (RT100-RT203) and one was smaller (RT100 only). Previous studies reported no phenotype-genotype correlation between RTS patients with or without a deletion. Our findings suggest a more severe phenotype. The mean age at presentation was 0.96 years in patients with a deletion as against 11.12 years in those without. Patients A and B with a deletion died in infancy which is rare in RTS and was not observed among the other patients. Patients A and D had accessory spleens, Patient A with hypoplastic left heart, abnormal pulmonary lobulation and renal agenesis. This is the second report of hypoplastic left heart and the first report of polysplenia with RTS. The signs suggest a developmental field defect (disturbance of laterality) either as a newly recognised pattern of RTS, or alternatively a novel contiguous gene syndrome.
19	Bercedo A, Cabero MJ, Garcia-Consuegra J, Hernado M, Yaez S, Fernandez-Llaca H. GENERALIZED LICHEN NITIDUS AND JUVENILE CHRONIC ARTHRITIS: AN UNDESCRIBED ASSOCIATION. Pediatr Dermatol 1999 Sep;16(5):406-425 (letter)	No abstract available.
20	Berkenstadt Michal, Dorit Lev, Reuven Achiron, Mordechay Rosner, Gad Barkai. Pulmonary agenesis, microphthalmia, and diaphragmatic defect (PMD): New syndrome or association? Am. J. Med. Genet. 86(1):6-8, 1999	We present the prenatal diagnosis of a 22-week-gestation fetus with unilateral pulmonary agenesis, diaphragmatic hernia, microphthalmia, pulmonary vessel agenesis, and intrauterine growth retardation. The association of pulmonary agenesis, diaphragmatic defect, and microphthalmia was described previously in two patients but the resemblance was not noted by the authors. While each case differs slightly in some of the associated anomalies, it is evident that the mainstay of diagnosis is similar to the case presented here and that this represents a new syndrome or association.
21	Bettinelli A, Rusconi R, Ciarmatori S, Righini V, Zammarchi E, Donati MA, Isimbaldi C, Bevilacqua M, Cesareo L, Tedeschi S, Garavaglia R, Casari G. Gitelman disease associated with growth hormone deficiency, disturbances in vasopressin secretion and empty sella: a new hereditary renal tubular-pituitary syndrome? Pediatr Res 1999 Aug;46(2):232-8	Gitelman disease was diagnosed in two unrelated children with hypokalemic metabolic alkalosis and growth failure (a boy and a girl aged 7 mo and 9.5 y, respectively, at clinical presentation) on the basis of mutations detected in the gene encoding the thiazide-sensitive NaCl cotransporter of the distal convoluted tubule. GH deficiency was demonstrated by specific diagnostic tests in both children. Hypertonic saline infusion tests showed a partial vasopressin deficiency in the girl and delayed secretion of this hormone in the boy. Magnetic resonance imaging revealed an empty sella in both cases. Up to now, hypomagnesemia and hypocalciuria have been considered obligatory criteria for the diagnosis of Gitelman disease; however, our two patients had hypomagnesemia and hypocalciuria in less than half the determinations. GH replacement treatment was associated with a good clinical response in both children. It appears that these cases represent a new phenotype, not previously described in Gitelman disease, and that the entity may be considered a new complex hereditary renal tubular-pituitary syndrome.
22	Bohring A, Silengo M, Lerone M, Superneau DW, Spaich C, Braddock SR, Poss A, Opitz JM. Severe end of Opitz trigonocephaly (C) syndrome or new syndrome? Am J Med Genet 1999 Aug;85(5):438-446	We report on four unrelated cases of an Opitz trigonocephaly (C)-like syndrome with a highly characteristic combination of facial anomalies including prominent metopic suture, exophthalmos, hypertelorism, cleft lip and palate, flexion deformities of the upper limbs and multiple other anomalies. We also review two very similar published cases formerly considered to have the C syndrome. Although there is overlap, a clinical distinction from the Opitz trigonocephaly and other syndromes seems possible, and thus a specific causal entity may be postulated.
23	Boles RG. Cleft palate, ptosis, digital anomalies and mental retardation: a new syndrome or a distal arthrogryposis variant? Clin Dysmorphol 1999 Jan;8(1):63-5	A case is presented of a female with cleft palate, digital anomalies and mental retardation. The case is compared with one already reported and possible diagnoses discussed. These cases appear to present a new syndrome or a variant of distal arthrogryposis.
24	Bonneau Dominigue, Martine Maréchaud, Sylvie Odent, Isabelle Piegay, Alain Godard, Patrizia Amati. Heterotaxy-neural tube defect and holoprosencephaly occurring independently in two sib fetuses. Am. J. Med. Genet. 84:373-376, 1999.	We report on two sib fetuses, products of a consanguineous union, who had multiple and apparently unrelated malformations. The first fetus, a female, had trilobed lungs, a single cardiac ventricle, asplenia, situs ambiguus of the liver, and a lumbosacral meningomyelocele. The brain of this fetus was normal. The second fetus, a male, had bilobed lungs, a single cardiac ventricle, situs solitus of the abdominal organs and spleen, and a semilobar holoprosencephaly. The occurrence of these malformations in sibs of different sexes and the parental consanguinity suggest a recessive mutation in a gene responsible for both heterotaxy and midline defects, including holoprosencephaly.
25	Brodie Steven G, Ralph S. Lachman, Margaret M. McGovern, Pertchoui B. Mekikian, William R. Wilcox. Lethal osteosclerotic skeletal dysplasia with intracellular inclusion bodies. Am. J. Med. Genet. 83:372-377, 1999	We report an apparently previously undescribed form of lethal osteosclerotic skeletal dysplasia in a 30-week male fetus with micromelic shortness of the limbs. Radiographic findings at necropsy included increased density in all bones, most marked in the skull, mandible, and pubis. The ribs were very short, abnormally modeled, and wide anteriorly. The vertebrae were posteriorly hypoplastic and wedged, particularly in the cervical and lumbar regions. The femora and tibiae were short with wide distal metaphyses, undermodeled diaphyses, and coxa vara. The humeri, radii, and ulnae were also short and undermodeled with proximal and distal flare. Chondro-osseous morphology showed short chondrocyte columns, extension of hypertrophic cells into the metaphysis, and overgrowth of perichondral bone. In the resting cartilage there were large chondrocytes containing a homogeneous material staining pink with von Kossa trichrome, gray with toluidine blue, and black with silver methenamine. The cortical bone was lacking and the trabecular bone was hypercellular, thick, and coarse. Ultrastructurally, the resting zone chondrocytes were large and round with condensed chromatin and dilated loops of rough endoplasmic reticulum. The radiographic and histopathologic findings in this case are unique and differ from those seen in other reported lethal osteosclerotic skeletal dysplasias.
26	Calin George, Juul Wijnen, Heleen van der Klift, Ana Ionita, Adri Mulder, Cor Breukel, Ron Smits, Hans Dauwerse, Kerstin Hansson, Steliana Calin, Dragos Stefanescu, Alexandru Oproiu & Riccardo Fodde. Marfan-like habitus and familial adenomatous polyposis in two unrelated males: a significant association? European Journal of Human Genetics, 1999, 7, 5, pp 609 - 614	Familial adenomatous polyposis (FAP) can be considered as a condition of the whole body as extracolonic features derived from all the three embryonic lineages are recorded with varying frequency in addition to the presence of multiple adenomas in the large intestine. Here, we describe two unrelated cases of FAP with unusual extracolonic phenotypes, namely several abnormalities of mesodermal origin strongly resembling Marfan syndrome (MFS) or a Marfan-like habitus. Conventional cytogenetic and FISH analysis did not reveal any gross chromosomal rearrangement on the long arm of chromosome 5 where the APC and FBN2 genes were located. However, in case 2 the FAP-causing mutation in the APC gene was found in the donor splice site of exon 4 and was shown to result in a frameshift and a premature termination codon. We propose that such connective tissue abnormalities may result from germline APC mutations in combination with specific genetic and/or environmental modifying factors.
27	Cario H, Bode H, Gustavsson P, Dahl N, Kohne E. A microdeletion syndrome due to a 3-Mb deletion on 19q13.2--Diamond-Blackfan anemia associated with macrocephaly, hypotonia, and psychomotor retardation.Clin Genet 1999, 55(6):487-492	We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.
28	Carpenter Nancy J, Yong Qu, Mary Curtis, Shivanand R. Patil. X-linked mental retardation syndrome with characteristic coarse facial appearance, brachydactyly, and short stature maps to proximal Xq. Am. J. Med. Genet. 85:230-235, 1999	We describe a three-generation family in which X-linked mental retardation (XLMR) is associated with minor facial anomalies and brachydactyly. Two brothers and four nephews have coarse facial appearance, brachydactyly with widening of the distal phalanges, short stature, and moderate mental retardation. The three obligate carrier women have normal intelligence and normal physical findings. The results of linkage analysis carried out in 1988 using restriction fragment length polymorphisms (RFLPs) were suggestive of linkage to DXYS1 and DXS101 in proximal Xq (Zmax = 1.63 at max = 0.0) [Carpenter et al., 1988: Am J Med Genet 43:A139]. The family was restudied with 16 microsatellite loci from Xp11.4 through Xq24. Linkage analysis demonstrated significant linkage to DXS1003, ALAS2, AR, DXS986, DXS990, DXS454, DXS1106, DXS1105, and DXS1220 from Xp11.3 to Xq23 (Zmax = 2.53 at max = 0.0). Recombinations detected between MAOB and DXS1055 and between DXS1220 and DXS1001 place the disease locus between Xp11.3 and Xq23. Among the genes known to map to this region is the XNP gene for the -thalassemia/mental retardation syndrome (ATR-X). This fact, along with the phenotypic similarity between our patients and ATR-X males, led us to consider XNP as a candidate gene for this family. X-inactivation studies provided further evidence for the involvement of XNP by showing completely skewed X-inactivation patterns in the three obligate carrier females, a pattern characteristic of carriers of XNP mutations.
29	Castriota-Scanderbeg Alessandro, Leopoldo Zelante, Salvatore Masala, Paolo Gasparini, Ralph S. Lachman. Acrodysplasia, severe ossification abnormalities with short stature, and fibular hypoplasia. Am. J. Med. Genet. 84:68-73, 1999	We present a girl with short stature, growth hormone neurosecretory dysfunction, severe hypoplastic/aplastic changes of the bones of the hands and feet with dysharmonic ossification, severely delayed bone age, microcrania, and fibular hypoplasia. Parental consanguinity suggests autosomal recessive inheritance. An additional three cases [Eiken et al., 1984: Eur J Pediatr 141:231-235] sharing some of the radiographic manifestations of this patient have been reported. However, distinctive findings in the present case seem to outline a separate entity.
30	Christianson Arnold L, Roger E Stevenson, C H van der Meyden, Julie Pelser, Francois W Theron, Petro L van Rensburg, Michael Chandler, Charles E Schwartz. X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet 1999;36:759-766	To date over 150 X linked mental retardation (XLMR) conditions have been documented. We describe a five generation South African family with XLMR, comprising 16 affected males and 10 carrier females. The clinical features common to the 16 males included profound mental retardation (100%), mutism despite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limited life expectancy (68.8%). Of the four affected males examined, all had mild craniofacial dysmorphology and three were noted to have bilateral ophthalmoplegia and truncal ataxia. Three of 10 obligate female carriers had mild mental retardation. Cerebellar and brain stem atrophy was shown by cranial imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10
31	Chudley Albert E, D.C. Tackels, Herbert A. Lubs, J. Fernando Arena, Wendi P. Stoeber, Sylvia Kovnats, Roger E. Stevenson, Charles E. Schwartz. X-linked mental retardation syndrome with seizures, hypogammaglobulinemia, and progressive gait disturbance is regionally mapped between Xq21.33 and Xq23. Am. J. Med. Genet. 85:255-262, 1999	We identified a family with three males in two generations with moderate mental retardation. The two oldest were first cousins whose mothers were sisters. The third affected was a grandson through a daughter of one of the sisters, strongly suggesting X- linked inheritance. The affected males had prominent glabella, synophrys, prognathism, generalized hirsutism, and bilateral single palmar creases. All developed seizures in childhood. The two oldest have had a slow deterioration in neurological status with poor gait and balance and progressive weakness. No deterioration in their mental status has been observed. The oldest had cerebellar atrophy confirmed on computed tomography and magnetic resonance imaging scans of the brain and prolonged nerve conduction velocity. Two of the males had hypogammaglobulinemia (IgA deficient). Two-point linkage analysis using 27 microsatellite markers on the X chromosome resulted in a maximum LOD score of 2.23 at = 0 for locus DSX101. Recombination was observed at locus DSX1170 in Xq21.33 and locus DXS8067 in Xq23. We conclude that this family represents an X-linked disorder associated with a recognizable phenotype, progressive neurological deterioration, and variable hypogammaglobulinemia. The gene appears to lie between Xq21.33 and Xq23
32	Chung WY, Chung LP. A case of oral-facial-digital syndrome with overlapping manifestations of type V and type VI: a possible new OFD syndrome. Pediatr Radiol 1999 Mar 30;29(4):268-271	We report a child with clinical and radiological manifestations characteristic of both V'aradi syndrome (oral-facial-digital syndrome type VI) and Thurston syndrome (oral-facial-digital syndrome type V). The findings have not been reported previously, and we believe that it represents a new variant.
33	Cohen PA, Kalifa G, Donoghue V, Adamsbaum C, Haddad F, Dubousset J. Ischio-vertebral dysplasia: a distinct entity. Pediatr Radiol 1999 Feb;29(2):131-4	BACKGROUND: Kyphoscoliosis is a complication of some bone dysplasias, including cleidocranial dysplasia. OBJECTIVES: We report a distinct disorder with defective ossification of the ischial rami, severe kyphoscoliosis and normal clavicles. Early recognition of this syndrome allows prevention of complications. MATERIALS AND METHODS: All patient cases (aged 1 day to 33 years) were selected according to the above criteria, with special attention to radiological findings, family history and follow-up (5-30 years). RESULTS: In all eight patients, we observed the following: (a) Severe thoracic scoliosis of early onset and rapid progression, leading to rotatory dislocation. Spinal cord compression occurred in four cases with respiratory problems related to chest deformity. (b) Bilateral and symmetrical incomplete ossification of the ischial rami. (c) Peculiar facies with retrognathia. (d) Normal clavicles. Three patients were from the same family (grandmother, mother and daughter). CONCLUSION: Ischio-vertebral dysplasia seems to represent a true entity, with radiological and genetic findings that make it distinct from cleidocranial dysostosis. The association of kyphoscoliosis and these pelvic abnormalities is specific for this condition. Neurological and respiratory complications can be avoided if the condition is recognised early and early treatment is instituted.
34	Corona-Rivera Roman J, Enrique Corona-Rivera, Alfredo Corona-Rivera, Moises Quiles-Corona, Ezequiel Velez-Gómez, Marco A. Arana-Gutiérrez. Infant with manifestations of oto-palato-digital syndrome type II and of Melnick-Needles syndrome. Am J Med Genet., 85,1, 1999, pp 79-81 (letter)	No abstract available.
35	Criado German Rodriguez, Antonio Pérez Aytés. Mobius sequence, hypogenitalism, cerebral, and skeletal malformations in two brothers. Am. J. Med. Genet. 86:492-496, 1999	Two brothers born to a healthy, consanguineous Spanish couple have a syndrome of Mobius sequence with involvement of cranial nerves V, VI, VII, IX, and XII, central nervous system malformations; characteristic face with creased earlobes, short philthrum, and a short, arched upper lip, skeletal anomalies with short sternum and delayed bone maturation, hypogenitalism, and profound mental retardation. We suggest that this is a new multiple congenital anomalies condition and mental retardation (MCA/MR) syndrome with autosomic recessive inheritance.
36	Dacou-Voutetakis C, Bazopoulou-Kyrkanidou E, Kyrkanides S, Pangalos C, Apostolakis A. Growth retardation, distinct oriental-like facies, glaucoma, brachydactyly, ventricular septal defect and speech disorder. An unknown entity. Genet Couns 1999;10(3):245-50	A caucasian boy with distinct oriental-like facies, short stature, brachydactyly, congenital ventricular septal defect, glaucoma, and speech disorder is reported. Routine laboratory tests, karyotype, and hormonal profile (IGF 1, growth hormone during provocative testing, thyroid hormones, prolactin, gonadotrophins) were normal. Radiologic skeletal survey did not disclose any abnormality. Both parents were apparently normal, but short in stature.
37	De Jonghe Peter, Vincent Timmerman, Eva Nelis, Els De Vriendt, Ann Löfgren, Chantal Ceuterick, Jean-Jacques Martin, Christine Van Broeckhoven. A Novel Type of Hereditary Motor and Sensory Neuropathy Characterized by a Mild Phenotype. Arch Neurol. 1999;56:1283-1288	Background Three loci for autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1) have been identified on chromosomes 17p11.2 (CMT1A), 1q21-q23 (CMT1B), and 10q21.1-q22.1 (designated here as CMT1D). The genes involved are peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), and the early growth response element 2 (EGR2), respectively. Probably a fourth locus (CMT1C) exists since some autosomal dominant HMSN I families have been excluded for linkage with the CMT1A and CMT1B loci. Four loci for autosomal dominant hereditary motor and sensory neuropathy type II (HMSN II) or Charcot-Marie-Tooth disease type 2 (CMT2) have been localized on chromosomes 1p35-p36 (CMT2A), 3q13-q22 (CMT2B), 7p14 (CMT2D), and 3p (HMSN-P). Objective To describe the clinical, electrophysiologic, and neuropathological features of a novel type of Charcot-Marie-Tooth disease. Patients and Methods We performed linkage studies with anonymous DNA markers flanking the known CMT1 and CMT2 loci. Patients and their relatives underwent clinical neurologic examination and electrophysiologic testing. In the proband, a sural nerve biopsy specimen was examined.Results Linkage studies excluded all known CMT1 and CMT2 loci. The clinical phenotype is mild and almost all affected individuals remain asymptomatic. Electrophysiologic and histopathological studies showed signs of a demyelinating neuropathy, but the phenotype is unusual for either autosomal dominant HMSN I or HMSN II. Conclusion Our findings indicate that the HMSN in this family represents a novel clinical and genetic entity.
38	de Ravel TJ, Berkowitz DE, Wagner JM, Jenkins T. Brachydactyly type B with its distinct facies and 'Cooks syndrome' are the same entity. Clin Dysmorphol 1999 Jan;8(1):41-5	A sibling pair with brachydactyly type B born to a normal non-consanguineous couple are described and the severity of their condition discussed. It is proposed that a subgroup of individuals with brachydactyly type B principally involving the nails and distal phalanges, and also having distinct facies, might be identical to individuals having 'Cooks syndrome'.
39	Degner D, Bleich S, Riegel A, Ruther E, [Orofaciodigital syndrome--a new variant? Psychiatric, neurologic and neuroradiological findings]. Fortschr Neurol Psychiatr 1999 Dec;67(12):525-8 [Article in German]	Oral-facial-digital (OFD) syndromes are a heterogeneous group of inherited syndromes that have in common anomalies of the face (median cleft lip), the tongue (bifid or lobulated tongue with harmartomas), and the digits (brachydactyly, polydactyly, syndactyly). Due to more or less subtle clinical features, at least seven causally different entities can be identified: 1) OFDS I; 2) OFDS II (Mohr syndrome); 3) OFDS III; 4) OFDS with tibial anomalies (OFDS IV); 5) OFDS V (Thurston syndrome); 6) OFDS VI (Varadi syndrome); and 7) OFDS VII (Whelan syndrome). The neuro-psychiatric clinical observations and MRI findings of a 40 year old woman with a OFD syndrome are described. The observed findings (leukoaraiosis, epilepsy, major depression) in combination with a proven OFD syndrome possibly reflect a new type of OFD syndrome.
40	Di Landro A, Tadini GL, Marchesi L, Cainelli T. Phakomatosis pigmentovascularis: A new case with renal angiomas and some considerations about the classification. Pediatr Dermatol 1999 Jan-Feb;16(1):25-30	We report phakomatosis pigmentovascularis detected in a Caucasian child characterized by the presence of a nevus flammeus and nevus anemicus on the face, a telangiectatic linear nevus of the right leg, and a very extensive blue spot covering 60% of the body surface, with ocular melanosis. Multiple angiomatous lesions of the kidney are associated without alterations of the central nervous system (CNS). This association has not been reported before; it could be a further expression of the complex of developmental defects. Our case corresponds exactly to type IIb in the classification of phakomatosis pigmentovascularis proposed by Hasegawa. As this classification seems very extensive, the higher incidence of cases corresponding to the second subtype suggests that we should identify it by the term phakomatosis pigmentovascularis, while the others could be considered as only very uncommon variants.
41	Di Rocco M, Arslanian A, Romanengo M, Dagna-Bricarelli F, Borrone C. Ataxia, ocular telangiectasia, chromosome instability, and Langerhans cell histiocytosis in a patient with an unknown breakage syndrome. J Med Genet 1999 Feb;36(2):159-60	An 8 year old boy who had Langerhans cell histiocytosis when he was 15 months old showed psychomotor regression from the age of 2 years. Microcephaly, severe growth deficiency, and ocular telangiectasia were also evident. Magnetic nuclear resonance imaging showed cerebellar atrophy. Alphafetoprotein was increased. Chromosome instability after x irradiation and rearrangements involving chromosome 7 were found. Molecular study failed to show mutations involving the ataxia-telangiectasia gene. This patient has a clinical picture which is difficult to relate to a known breakage syndrome. Also, the relationship between the clinical phenotype and histiocytosis is unclear.
42	Dobyns William B, Elizabeth Berry-Kravis, Nancy J. Havernick, Kenton R. Holden, David Viskochil. X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. Am. J. Med. Genet. 86(4):331-337, 1999.	Lissencephaly has been described in over 10 distinct malformation syndromes. Recently, we have recognized 5 children from four unrelated families with an almost identical disorder comprising lissencephaly with a posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset epilepsy, hypothalamic dysfunction including deficient temperature regulation, and ambiguous genitalia in genotypic males. Our observation of 5 affected males in one of these families is consistent with an X-linked pattern of inheritance. However, it differs in many regards from the X-linked form of isolated lissencephaly sequence that is associated with mutations of the XLIS (DCX) gene. Therefore, we propose that this disorder comprises a new X-linked malformation syndrome, which we refer to as X-linked lissencephaly with ambiguous genitalia (XLA-G).
43	Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg's syndrome with facial palsy and lingua plicata: is that a new type of disease? Cutis 1999 Mar;63(3):139-41	No abstract available.
44	Enns Gregory M, Elizabeth Roeder, Ruth T. Chan, Zohra Ali-Khan Catts, Victoria A. Cox, Mahin Golabi. Apparent cyclophosphamide (cytoxan) embryopathy: A distinct phenotype? Am. J. Med. Genet. 86:237-241, 1999.	Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in animals, but population studies have not conclusively demonstrated teratogenicity in humans. Six isolated reports of prenatally exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to document a new case of in utero CP exposure with multiple congenital anomalies and to establish an apparent CP embryopathy phenotype. The mother had systemic lupus erythematosus and cyclophosphamide exposure in the first trimester. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, and potassium chloride throughout pregnancy. The infant had growth retardation and multiple anomalies including microbrachycephaly, coronal craniosynostosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, small, abnormal ears, unilateral preauricular pit, broad, flat nasal bridge, microstomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported cases of in utero exposure to cyclosposphamide shared the following manifestations with our patient: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly. We conclude that (a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question.
45	Faivre Laurence, Anne-Lise Delezoide, Françoise Narcy, Féréchté Razavi, Raymonde Bouvier, Valérie Cormier-Daire, Marie-Louise Briard, Stanislas Lyonnet, Michel Vekemans, Arnold Munnich, Martine Le Merrer. A new lethal syndrome of exomphalos, short limbs, and macrogonadism. J Med Genet 1999;36(2):131-136	Exomphalos is a defect in the ventral abdominal wall with herniation of the abdominal viscera through a widened umbilical ring covered by a sac consisting of amnion and lined by peritoneum. The incidence of exomphalos is about 2.5 per 10 000 live births.1 It can be found in several multiple congenital abnormality (MCA) syndromes. The best known and documented syndrome including exomphalos associated with other abnormalities is the Beckwith-Wiedemann syndrome. Here we report on seven fetuses with a novel MCA syndrome consisting of exomphalos, short limbs with uncommon metaphyseal abnormalities, and macrogonadism, and we particularly emphasise the clinical differences between this syndrome and the Beckwith-Wiedemann syndrome.
46	Fryns JP, Dumoulin M, Hens G. Progeroid syndrome with facial teleangiectatic erythema, posterior subcapsular cataracts, calcification of basal ganglia and atrium septum defect type 2 Genet Couns 1999;10(4):395-8	In this report we present the long-term follow-up findings in a young female born to consanguineous parents with the unique association of (1) a progeroid syndrome, (2) facial dysmorphism with relative microcephaly, triangular face, retrognathism and skin erythema, (3) bilateral posterior cataracts, (4) basal ganglia calcifications and (5) atrium septum defect type 2. Intelligence is borderline. Clinical evolution after normal puberty was positive with regression of the facial erythematous changes. Over the years differential diagnosis included progeria, hypohidrotic ectodermal dysplasia, Rothmund-Thompson syndrome, Cockayne syndrome, Bloom syndrome, but the clinical spectrum of abnormalities and the evolution with age were not compatible with one of these diagnoses. Parental consanguinity is in favour of autosomal recessive inheritance.
47	Fujiwara Ikawa, Yoshiaki Kondo, Kazuie Iinuma. Oral-facial-digital syndrome with hypothalamic hamartoma, postaxial ray hypoplasia of the limbs, and vagino-cystic communication: A new variant? Am. J. Med. Genet. 83(2):77-81, 1999	We report on a 20-month-old girl with hypothalamic hamartoma, left cerebral atrophy, tongue nodules, oral frenula, micrognathia, hypoplasia of the left ulna, the fibulae, and right tibia, polysyndactyly of the hands and feet, vagino-cystic drainage with hydrometrocolpos, megaloureters, and hydronephrosis, agenesis of urethra, complex partial seizures, and central precocious puberty. The differential diagnosis is discussed. We conclude that the malformation complex in this girl is an oral-facial-digital syndrome, but is different from any of the 11 known subtypes.
48	Gelb Bruce D, Jian Zhang, Robert J. Sommer, Jared M. Wasserman, Milton J. Reitman, Judith P. Willner. Familial patent ductus arteriosus and bicuspid aortic valve with hand anomalies: A novel heart-hand syndrome. J. Med. Genet. 87(2):175-179, 1999	The association between cardiac and limb defects, particularly those affecting the hand, has been well documented by the delineation of several heart-hand syndromes. Based on observations with a three-generation family with seven affected individuals, we describe a novel heart-hand syndrome comprising patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplasia, and brachydactyly. The inheritance pattern was consistent with autosomal dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes. Because this new syndrome closely resembled Char syndrome (patent ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor facial anomalies), multipoint linkage analysis was performed using polymorphic DNA markers spanning the recently identified Char syndrome critical region at chromosomal bands 6p12-p21.1. This analysis formally excluded this 3-cM region, documenting that the two traits are not allelic. In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as well as an ulnar ray derivative has been identified. Because the hand anomalies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait.
49	Gentile M, Fiorente P. Esophageal, duodenal, rectoanal and biliary atresia, intestinal malrotation, malformed/hypoplastic pancreas, and hypospadias: further evidence of a new distinct syndrome. Am J Med Genet 1999 Nov 5;87(1):82-3 (letter)	No abstract available.
50	Grosso S, Cioni M, Pucci L, Morgese G, Balestri P. Selective mutism, speech delay, dysmorphisms, and deletion of the short arm of chromosome 18: a distinct entity? J Neurol Neurosurg Psychiatry 1999 Dec;67(6):830-1 (letter)	No abstract available.
51	Guion-Almeida Maria Leine, Roseli Maria Zechi-Ceide, Antonio Richieri-Costa. Multiple congenital anomalies syndrome: Growth and mental retardation, microcephaly, preauricular skin tags, cleft palate, camptodactyly, and distal limb anomalies. Report on two unrelated Brazilian patients. Am. J. Med. Genet. 87:72-77, 1999	We report on 2 unrelated Brazilian patients, born to non-consanguineous parents, both with multiple anomalies including growth and mental retardation, microcephaly, telecanthus, cleft palate, preauricular skin tags/pit, camptodactyly, and foot anomalies. To our knowledge, this is a previously undescribed formal genesis syndrome. Clinical and genetic aspects are discussed.
52	Guion-Almeida ML, Richieri-Costa A. Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation, and CNS structural anomalies. A new syndrome? Clin Dysmorphol 1999 Jan;8(1):1-4	We report a Brazilian girl, born to normal and non-consanguineous parents and presenting, among other signs, brachyacrocephaly, a wide forehead, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, a broad and high nasal root, an absent nasal tip, a wide columella, a long and smooth philtrum, a carp-like mouth, macrostomia, a thin upper lip with midline notching, submucous cleft of the soft palate, a small and grooved chin, ear anomalies, Dandy-Walker anomaly, a structural anomaly of the corpus callosum, grey matter heterotopia, and mental retardation. The whole clinical picture of the present patient suggests a 'new' type of frontonasal dysplasia and main differential diagnosis includes the acrofrontofacionasal dysostosis 2 syndrome (MIM 201181). Other differential diagnoses are discussed.
53	Guion-Almeida ML, Richieri-Costa A. New syndrome of growth and mental retardation, structural anomalies of the central nervous system, and first branchial arch, anophthalmia, heminasal a/hypoplasia, and atypical clefting: report on four Brazilian patients. Am J Med Genet 1999 Nov 26;87(3):237-44	We report on four unrelated Brazilian patients with growth and mental retardation, structural anomalies of the central nervous system (CNS), mainly callosal agenesis, prominent forehead, facial asymmetry, anophthalmia, heminasal a/hypoplasia, preauricular skin tags, structural anomalies of the external ears, and atypical clefting. This combination of anomalies is unique and, to our knowledge, is a previously undescribed syndrome of unknown etiology, although one of the patients was born to a consanguineous couple, suggesting the possibility of autosomal recessive inheritance. Clinical, genetic, and differential diagnosis aspects are discussed.
54	Hameed R, Bissenden JG, Webb WR, Cole TR. An apparently new acrocraniofacial syndrome with cranial nerve and visceral anomalies. Clin Dysmorphol 1999 Jul;8(3):199-202	We report details of a neonate with cranial bone dysplasia, broad nasal bridge, microphthalmia, optic and olfactory nerve anomalies, pulmonary segmentation defects, polydactyly, abnormally positioned and shaped thumbs, absent mesentery to the gut and streak gonads. Review of the literature and relevant databases does not identify a likely diagnosis.
55	Hamel Ben CJ, Pieter Wesseling, Willy O Renier, Bellinda van den Helm, Hans-Hilger Ropers, Hannie Kremer, Edwin C M Mariman. A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region. J Med Genet 1999;36(2):140-143	We report on a family with an X linked neurodegenerative disorder consisting of mental retardation, blindness, convulsions, spasticity, and early death. Neuropathological examination showed mild hypomyelination. By linkage analysis, the underlying genetic defect could be assigned to the pericentromeric region of the X chromosome with a maximum lod score of 3.30 at =0.0 for the DXS1204 locus with DXS337 and PGK1P1 as flanking markers.
56	Happle R, Kuster W. Nevus psiloliparus: a distinct fatty tissue nevus. Dermatology 1998;197(1):6-10	BACKGROUND: Encephalocraniocutaneous lipomatosis is usually associated with a peculiar type of fatty tissue nevus which represents a smoothly surfaced and hairless lesion involving the scalp. This disorder has so far not been recognized as a cutaneous entity. OBJECTIVE: The purpose of this article is to describe the characteristic features of this nevus and to give it a name. METHOD: From the study of two cases and from a review of the literature we delineate the clinical and histopathological criteria of this disorder for which we propose the term 'nevus psiloliparus'. This name is derived from the Greek words psilos = hairless and liparos = fatty, and describes the two most characteristic features of the disorder. RESULTS: A comprehensive comparison shows that nevus psiloliparus can be distinguished from other types of fatty tissue nevi by clinical criteria such as localization on the scalp, a flat smooth surface and absence of hair follicles, by the histopathological feature of isolated arrector pili muscles and by the presence of associated extracutaneous features in the form of encephalocraniocutaneous lipomatosis. In particular, nevus psiloliparus can be separated from the Hoffmann-Zurhelle nevus that has so far never been observed in cases of encephalocraniocutaneous lipomatosis. CONCLUSION: The presently available data suggest that nevus psiloliparus represents a distinct cutaneous entity. Future clinical and genetic research should show whether this concept holds true.
57	Happle Rudolf. Elattoproteus syndrome: Delineation of an inverse form of Proteus syndrome.Am. J. Med. Genet. 84:25-28, 1999	A 7-year-old boy had partial lipohypoplasia and patchy dermal hypoplasia involving large areas of his body. These areas of deficient growth were similar to those described in many cases of Proteus syndrome. Paradoxically, however, he had only few and rather mild lesions of disproportionate overgrowth. This unusual case is taken as a clue to postulate the Elattoproteus syndrome, an inverse form of Proteus syndrome. The paradoxical coexistence of hyperplastic and hypoplastic lesions may reflect a twin spot phenomenon. The patient would carry at the Proteus locus one allele giving rise to overgrowth of tissues (Pleioproteus allele - from Greek pleion, meaning plus), whereas the other allele would cause deficient growth of tissues (Elattoproteus allele - from Greek elatton, meaning minus). At an early stage of embryogenesis, somatic recombination would give rise to two different populations of cells homozygous for either allele. From a heuristic point of view, one may postulate the existence of the Elattoproteus syndrome, a purely inverse form of Proteus syndrome that would develop in the absence of the Pleioproteus allele.
58	Harth W, Linse R. Keratosis follicularis spinulosa decalvans associated with patent ductus arteriosus and hypospadia in an Asiatic patient. Hautarzt, 50(4):295-8 1999	Keratosis follicularis spinulosa decalvans (KFSD) appeared sporadically in an Asian boy, who also presented with naevus teleangiectaticus lateralis, patent ductus arteriosus (Botalli) and hypospadia. The association of these findings raises the question of a new syndrome. In addition, this is the first report of KFSD in a patient of Asian origin.
59	Hoveyda Nourieh, Julian P H Shield, Christine Garrett, W K `Kling' Chong, Kathryn Beardsall, Esi Bentsi-Enchill, Harish Mallya, Michael H Thompson. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome. J Med Genet 1999;36:700-704	Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.
60	Janssen HCJP, C Schaap, N Vandevijver, P Moerman, C E M de Die-Smulders, J-P Fryns. Two sibs with microcephaly, hygroma colli, renal dysplasia, and cutaneous syndactyly: a new lethal MCA syndrome? J Med Genet 1999;36(6):481-484	We report two sibs of Turkish descent with multiple congenital anomalies including severe microcephaly, hygroma colli, cystic renal dysplasia, and bilateral cutaneous syndactyly of toes IV-V. In addition, the second sib presented with bilateral fusion of the eyelids, a bicornuate uterus, and clitoromegaly. The parents are first cousins, which suggests autosomal recessive inheritance. In reviewing previously published reports, several cases were found with cerebral, renal, and digital anomalies as the main features. Several of the additional symptoms present in the second sib were suggestive of Fraser syndrome, but the severe microcephaly in both sibs is unusual. The differential diagnosis is discussed, including the possibility of an entirely new entity in the broad spectrum of syndromes with cerebral, renal, and digital anomalies.
61	Kato M, Takizawa N, Yamada S, Ito A, Honma T, Hashimoto M, Saito E, Ohta T, Chikaoka H, Hayasaka K. Diffuse pachygyria with cerebellar hypoplasia: a milder form of microlissencephaly or a new genetic syndrome? Ann Neurol 1999 Oct;46(4):660-3	We report on 2 families with diffuse pachygyria and cerebellar hypoplasia, who presented hypotonia, ataxia, seizures, and developmental delay since infancy. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed decreased gyral formation in the cerebral cortex and marked hypoplasia in the cerebellum. Cerebellar hypoplasia is often associated with type 2 lissencephaly; however, our cases showed no polymicrogyria, and their clinical findings were quite mild compared with those of microlissencephaly. Their characteristic phenotype suggested a new genetic syndrome, which was possibly inherited as an autosomal recessive trait.
62	Kawame H, Sugio Y, Fuyama Y, Hayashi Y, Suzuki H, Kurosawa K, Maekawa K. Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature. J Hum Genet 1999;44(4):219-24	We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.
63	Kelly Thaddeus E, Kathy Amoroso, Merry Ferre, John Blanco, Patricia Allinson, Thomas W. Prior. Spinal muscular atrophy variant with congenital fractures. Am. J. Med. Genet. 87:65-68, 1999	A single report of brothers born to first-cousin parents with a form of acute spinal muscular atrophy (SMA) and congenital fractures suggested that this combination represented a distinct form of autosomal recessive SMA. We describe a boy with hypotonia and congenital fractures whose sural nerve and muscle biopsies were consistent with a form of spinal muscular atrophy. Molecular studies identified no abnormality of the SMNT gene on chromosome 5. This case serves to validate the suggestion of a distinct and rare form of spinal muscular atrophy while not excluding possible X-linked inheritance.
64	Kirk Edwin PE, Susan Arbuckle, Phillip L. Ramm, Lesley C. Adès. Severe micrognathia, cleft palate, absent olfactory tract, and abnormal rib development: Cerebro-costo-mandibular syndrome or a new syndrome? Am. J. Med. Genet. 84:120-124, 1999	We report on a family in which two sibs had apparently absent ribs and severe micrognathia on prenatal ultrasonography. The pregnancies were terminated at 19 and 12 weeks of gestation, respectively. Autopsy findings in the first fetus (19 weeks of gestation) included severe micrognathia, a U-shaped defect of the soft palate, marked postnuchal edema, absent olfactory bulbs, and cribriform plate and rib abnormalities. The ribs consisted of cartilage anteriorly, with only a small amount of fibrous tissue present laterally and posteriorly. The second fetus (12 weeks gestation) had agnathia, with a large U-shaped defect in the soft palate. There was moderate postnuchal edema. The ribs were unossified and there were gaps in the cartilage where primitive mesenchyme was present posteriorly and laterally. These findings are consistent with a severe form of cerebro-costo-mandibular syndrome. The early fetal histopathology of both cases suggests a possible mechanism by which the characteristic rib gaps of cerebro-costo-mandibular syndrome may develop, with evidence for abnormal function of a gene or genes involved in regulation of rib chondrogenesis.
65	Kirk EP, Wilson M. Dominant inheritance of cleft palate with minor abnormalities of hands and feet: a new syndrome? Clin Dysmorphol 1999 Jul;8(3):193-7	We report a family in which four members of three generations are affected by median cleft palate. The proband and her mother have additional features including bilateral single transverse palmar creases, broad great toes and hypoplastic fifth toenails. Dominant isolated cleft palate has rarely been reported, and there are no previous reports of dominant cleft palate with these associated features. We believe that this represents a previously unreported syndrome, which needs to be considered when assessing recurrence risk for cleft palate.
66	Koyluoglu G, Percin EF. An infant with situs inversus totalis, branchial cleft cyst and ectopic kidney: a new combination? Clin Dysmorphol 1999 Jul;8(3):233-4 (letter)	No abstract available.
67	Kozlowski K, Bieganski T, Gardner J, Beighton P. Osteochondrodystrophies with marked platyspondyly and distinctive peripheral anomalies. Pediatr Radiol 1999 Jan;29(1):1-5	Two patients with a unique generalised bone dysplasia demonstrating severe distinctive platyspondyly are reported. This group of crippling disorders defies metabolic and histological classification. The radiographic examination is, at present, the only practical method of documentation of these rare disorders.
68	Kozlowski K, Czerminska-Kowalska A, Kulczycka H, Rowinska E, Pronicka E. Dominantly inherited isolated hyperparathyroidism: a syndromic association? Pediatr Radiol 1999 Jan;29(1):10-5	Dominantly inherited isolated hyperparathyroidism (DIIH) is rare in childhood. It may be the first biochemical abnormality in the multiple endocrine neoplasia type I (MEN I) and type II (MEN II) syndromes. Its clinical course is usually asymptomatic or of low morbidity. Radiographic examination is most often normal. We describe six members of a family with distinctive phenotype and DIIH. Limited systemic symptoms and severe radiographic osteitis fibrosa cystica were further unusual features in this family. The diagnosis of DIIH was made only after a 9-year-old girl developed hypercalcaemic crisis after a pathological femoral fracture. Distinctive phenotype, unusual clinical course and unparalleled radiographic changes suggest a not yet described syndromic association.
69	Kozlowski K, Masel J. Mesomelic dysplasia with periosteal thickening, radio-humeral dislocation, osteoporosis and multiple fractures. Eur J Pediatr 1999 Apr;158(4):308-11	We report a boy with a new form of mesomelic dysplasia characterised by short stature, multifocal periosteal thickening, radio-humeral dislocation, osteoporosis and multiple fractures with minimal trauma. Electrophoresis of fibroblast collagens detected defects in type III and type V collagen. CONCLUSION: Bone dysplasias presenting with osteopenia, abnormal trabecular pattern, bone fragility, and periosteal thickening suggest a collagenopathy. A possible collagen defect requires biochemical investigations.
70	Kumar D. A case of lateral facial clefts with Fallot tetralogy, duodenal stenosis and intestinal malrotation: a new multiple congenital anomaly syndrome? Clin Dysmorphol 1999 Jan;8(1):19-21	Multiple congenital malformations in a Caucasian female infant are described which include lateral facial clefts, malformed external ears, cleft palate, Fallot tetralogy, duodenal stenosis and intestinal malrotation. There were no associated limb or spinal anomalies. This case appears to be an example of a new multiple congenital anomaly syndrome.
71	Lacassie Yves, Marta I. Arriaza, M. Caroline Duncan, Cristino Dijamco, Catherine McElveen, Paul F. Stahls III. Identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E: a new syndrome or variant of Fitzsimmons-Guilbert syndrome? Am. J. Med. Genet. 84:90-93, 1999	We report on concordantly affected female identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E. The most similar condition reported is the syndrome described by Fitzsimmons and Guilbert in uniovular twins characterized by progressive spastic paraplegia, dysarthria, brachydactyly type E, and cone-shaped epiphyses. During the last 11 years a report of only one other patient with this syndrome has been published; hence, its phenotypic delineation may be only partial. Although our patients might expand the phenotypic spectrum of this syndrome, they may represent a new disorder.
72	Limwongse Chanin, Richard E. Wyszynski, Lois H. Dickerman, Nathaniel H. Robin. Microcephaly-lymphedema-chorioretinal dysplasia: A unique genetic syndrome with variable expression and possible characteristic facial appearance. Am. J. Med. Genet. 86:215-218, 1999	We report on a follow-up examination of a family with microcephaly and lymphedema. The finding of chorioretinal dysplasia with variable visual deficit in multiple relatives, which was not previously discovered, supports the concept of microcephaly, lymphedema, and chorioretinopathy as being a single autosomal dominant genetic entity with variable expression. We recommend that fundoscopic examination be performed in all patients with microcephaly with or without lymphedema.
73	Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI, Sovik O. A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet 1999 Oct;8(11):2001-8	Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor (HNF)-1beta are the cause of one form of maturity-onset diabetes of the young (MODY), type 5 (MODY5). We have studied a Norwegian family, N5, with a syndrome of mild diabetes, progressive non-diabetic renal disease and severe genital malformations. The sequence of the HNF-1beta gene ( TCF2 ) revealed a 75 bp deletion in exon 2 (409-483del) which would result in the synthesis of a protein lacking amino acids Arg137 to Lys161 (R137-K161del). This deletion is located in the pseudo-POU region of HNF-1beta, a region implicated in the specificity of DNA binding. Functional studies of R137-K161del HNF-1beta revealed that it could not bind an HNF-1 target sequence or stimulate transcription of a reporter gene indicating that this is a loss-of-function mutation. The R137-K161del allele co-segregated with diabetes and renal disease in pedigree N5. In addition, two of four female carriers with this mutation had vaginal aplasia and rudimentary uterus (Mullerian aplasia). These studies strongly suggest that heterozygous mutations in the HNF-1beta gene are associated with a syndrome characterized by MODY and severe, non-diabetic renal disease. Moreover, the presence of internal genital malformations in two females suggests that additional clinical features may be associated with HNF-1beta mutations.
74	Lord RS, Chambers AJ. Familial carotid body paragangliomas and sensorineural hearing-loss: a new syndrome. Cardiovasc Surg 1999 Jan;7(1):134-8	BACKGROUND: Carotid body paragangliomas are rare tumors that are sometimes familial, the transmission of which is thought to be by genomic imprinting. We have treated a family who exhibited co-inheritance of carotid body paraganglioma and sensorineural hearing-loss, a relationship that has not been previously reported. METHODS: We studied a large Australian family who exhibited familial carotid body paragangliomas, many of whose members also suffered tinnitus or hearing-loss. This relationship was examined by reviewing the medical records of family members with confirmed tumors, carrying out neck ultrasonic scanning or computed tomography on their relatives to look for previously unrecognized tumors, and arranging audiometric testing. This information was used to characterize the type of hearing-loss present in this family and to construct a pedigree for the two traits. RESULTS: The hearing-loss observed in this family was sensorineural in character. Of 15 family members studied over four generations, eight were confirmed positive for both carotid body paraganglioma and sensorineural hearing-loss, two for the tumor only (one of whom did not have his hearing assessed) and one for hearing-loss alone. Four family members were negative for both traits. CONCLUSIONS: The pedigree provides evidence of a previously undescribed association between familial carotid body paraganglioma and sensorineural hearing-loss, a combination that appears to be co-inherited in this family.
75	Lubke T, Marquardt T, von Figura K, Korner C. A New Type of Carbohydrate-deficient Glycoprotein Syndrome Due to a Decreased Import of GDP-fucose into the Golgi. J Biol Chem 1999 Sep 10;274(37):25986-25989	The fucosylation of glycoproteins was found to be deficient in a patient with a clinical phenotype resembling that of leukocyte adhesion deficiency type II (LAD II). While in LAD II hypofucosylation of glycoconjugates is secondary to an impaired synthesis of GDP-fucose due to a deficiency of the GDP-D-mannose-4,6-dehydratase, synthesis of GDP-fucose was normal in our patient (Korner, C., Linnebank, M., Koch, H., Harms, E., von Figura, K., and Marquardt, T. (1999) J. Leukoc. Biol., in press). Import of GDP-fucose into Golgi-enriched vesicles was composed of a saturable, high affinity and a nonsaturable component. In our patient the saturable high affinity import of GDP-fucose was deficient, while import of UDP-galactose and the activity of GDPase, which generates the nucleoside phosphate required for antiport of GDP-fucose, were normal. Addition of L-fucose to the medium of fibroblasts restored the fucosylation of glycoproteins. We propose that this new form of carbohydrate-deficient glycoprotein syndrome is caused by impaired import of GDP-fucose into the Golgi.
76	Lubs Herbert, Fatima Abidi, Jo-Ann Blaymore Bier, Diane Abuelo , Lisbeth Ouzts, Kytja Voeller, Eileen Fennell, Roger E. Stevenson, Charles E. Schwartz, Fernando Arena. XLMR syndrome characterized by multiple respiratory infections, hypertelorism, severe CNS deterioration and early death localizes to distal Xq28. Am. J. Med. Genet. 85:243-248, 1999	We report on a family with severe X-linked mental retardation (XLMR) and progressive, severe central nervous system deterioration. Three of the five affected males died of secondary complications before the age of 10 years and none have survived past the age of 10. These complications included swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections. In addition, hypotonia and a mild myopathy were also present. All had a characteristic facies, including downslanting palpebral fissures, hypertelorism, and a short nose with a low nasal bridge. The two older boys showed cerebral atrophy by CT. No metabolic abnormalities were identified. Three obligate carriers had an IQ less than 80. The causal gene has been localized distal to DXS8103 in Xq28, a region spanning 5cM. No other XLMR disorder with these manifestations have been localized to this region and this appears to be a new disorder.
77	Medeiros LJ, Palmedo G, Krigman HR, Kovacs G, Beckwith JB. Oncocytoid renal cell carcinoma after neuroblastoma: a report of four cases of a distinct clinicopathologic entity. Am J Surg Pathol 1999 Jul;23(7):772-80	Four children who developed oncocytoid renal cell carcinoma (RCC) after neuroblastoma are reported. One patient had multiple, bilateral RCCs. The mean age at time of diagnosis of RCC was 8.8 years (range, 5-13 years). The mean interval between neuroblastoma and RCC was 7.15 years (range, 3.1-11.5 years). The histologic findings of these RCCs did not fit within the spectrum of known renal epithelial neoplasms. Most of the neoplastic cells in all cases had eosinophilic, oncocytoid cytoplasm and were arranged in solid and papillary growth patterns. A subset of cells with reticular cytoplasm was also present. Immunohistochemical studies demonstrated keratins 8 and 18 in all neoplasms and keratin 20 in two cases. DNA ploidy analysis revealed that two of three neoplasms assessed were aneuploid. Cytogenetic studies revealed 45, XX, add or dup (7)(q32q36) in one neoplasm, and 83-89, XXXX, -1 ,-3, del (3)(q11.1q2?1), der(4)t(4;?22) (q32;q11.2), -14, -22 in a second tumor. Microsatellite polymerase chain reaction analysis detected no abnormalities in one neoplasm and allelic imbalance of chromosomes 2p31-32.2, 8p22, 9p22-24, 13q22, 20q13, and 22q11 in a second tumor. In case 4, two different RCCs excised 6 months apart were analyzed. The initial neoplasm showed allelic imbalance of chromosomes 2q31-32.2, 5q22, 5q31, 10p13-14, 13q22, 14q31, and 20q13. The subsequent neoplasm showed allelic imbalance of chromosomes 3p21.3, 14q31, and 20q13. The common presence of 14q31 and 20q13 abnormalities suggests that these two neoplasms were genetically related. In aggregate, these findings are distinctive, are not found in known types of RCC, and support the morphologic impression that oncocytoid RCC after neuroblastoma is a distinct clinicopathologic entity.
78	Megarbane A, Choueiri R, Bleik J, Mezzina M, Caillaud C. Microcephaly, microphthalmia, congenital cataract, optic atrophy, short stature, hypotonia, severe psychomotor retardation, and cerebral malformations: a second family with micro syndrome or a new syndrome? J Med Genet 1999 Aug;36(8):637-40	We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed.
79	Megarbane A, Khalil G, Waked N, Rotig A, Caillaud C, Loiselet J. Two sibs with myoclonic epilepsy, congenital deafness, macular dystrophy, and psychiatric disorders. Am J Med Genet 1999 Dec 3;87(4):289-93	We present a family with four children born to second-cousin parents. Two of the children had myoclonic epilepsy, congenital deafness, a dystrophic pattern of the macular pigment epithelium, incomplete right bundle branch block, and psychiatric disorders appearing after fever episodes. Results of all laboratory investigations including mitochondrial DNA analysis were normal. Despite the fact that this condition resembles one reported by Latham and Munro in 1937, it is possible that we might be reporting on a new autosomal recessive syndrome.
80	Mégarbané Andre, Edouard Stephan, Roland Kassab, Ramzi Ashoush, Nabiha Salem, Patrice Bouvagnet, Jacques Loiselet. Autosomal dominant secundum atrial septal defect with various cardiac and noncardiac defects: A new midline disorder. Am. J. Med. Genet. 83(3):193-200, 1999	We report on a Lebanese family in which 12 persons had an atrial septal defect and various cardiac and noncardiac anomalies. Cardiac anomalies are left axis deviation of QRS, right bundle branch block, atrial fibrillation, Wolff-Parkinson-White syndrome, nodal atrioventricular rhythm, aortic stenosis, pulmonic valve stenosis, mitral stenosis (Lutembacher syndrome), and low implantation of the tricuspid valve (Ebstein disease). Noncardiac abnormalities consisted specially of the presence of hypertelorism, cleft lip, and pectus excavatum. This combination appears to constitute a hitherto undescribed autosomal dominant midline disorder of the heart and upper half of the body with almost full penetrance and variable expressivity. The mutation does not map to any known locus involved in atrial septal defect or conduction block.
81	Megarbane A, Farah CB, Nabbout R. Unknown syndrome in two male sibs with hypotonia, ptosis, hand malformations, 2/3 toes syndactyly, and mental retardation. Genet Couns 1999;10(2):183-8	We report two brothers from nonconsanguineous parents who share hypotonia, ptosis, high arched palate, camptodactyly, fifth fingers clinodactyly, 2/3 toes syndactyly and psychomotor retardation. Differential diagnosis, such as the Ohdo syndrome, the Morillo-Cucci syndrome, the Marden-Walker-like syndrome, and the Frydman syndrome and discussed.
82	Mégarbané Andre, Soha Haddad-Zebouni, Rima Nabbout, Antoine H. Khoury, Elias I. Traboulsi. Microcephaly, colobomatous microphthalmia, short stature, and severe psychomotor retardation in two male cousins: A new MCA/MR syndrome? Am J Med Genet 1999 Mar 12;83(2):82-7	We report on 2 male cousins with minor facial anomalies, microcephaly, colobomatous microphthalmia, psychomotor retardation, short stature, and skeletal malformations. The children belong to a highly inbred family. We conclude that these patients have a previously undescribed autosomal-recessive syndrome.
83	Mégarbané Andre, Valérie Delague, Nabiha Salem, Jacques Loiselet. Autosomal recessive congenital cerebellar hypoplasia and short stature in a large inbred family. Am J Med Genet 1999 Nov 5;87(1):88-90 (letter)	No abstract available.
84	Mubashir MA, Sabry MA, Farah S, Haseeb N, Quasrawi B, al-Busairi W, al-Dabbous R, al-Awadi SA, Farag TI. New syndromic entity of situs inversus totalis. Clin Dysmorphol 1999 Jan;8(1):23-27	A 22-year-old Bedouin female with MCA/MR has been recently ascertained. She showed profound mental retardation, proportionate short stature, facial dysmorphism, spastic quadreparesis, bilateral taliper equinovarus, brachydactyly, situs inversus totalis, and MRI findings of cerebellar/midbrain migration defects. The described phenotype represents a new syndromic situs inversus with a characteristic Facio-Cerebro-Skeleto-Cardiac phenotype.
85	Michaels L, Lee K, Manuja SL, Soucek SO. Family with low-grade neuroendocrine carcinoma of salivary glands, severe sensorineural hearing loss, and enamel hypoplasia. Am. J. Med. Genet. 83:183-186, 1999	Four sibs in a family on the Isle of Man, two brothers and two sisters ranging in age from 33 to 45 years, presented with low-grade malignant tumors of the submandibular gland in three cases and of the nasal cavities and maxillary sinuses in one. The neoplasms were all of the same histological type, apparently hitherto undescribed, showing well-differentiated neoplastic ducts, surrounded by neoplastic myoepithelial cells, together with sheets of epithelial cells expressing neuroendocrine markers by immunohistochemistry. Cervical neck node metastases have developed in all four cases. In the sib with a primary sinonasal neoplasm, widespread bloodstream metastases also became manifest and a single such metastasis in his brother. All four sibs have severe enamel hypoplasia and the same lesion is present in 5 of their 11 children. In the two male patients, severe sensorineural hearing loss has developed in adult life, unilateral in the left ear in one brother, bilateral in the other. In the brother with bilateral sensorineural hearing loss, magnetic resonance imaging revealed a vestibular schwannoma on the left side, which is currently under treatment. The inherited hearing loss is thought to be unilateral in this case also.
86	Mingarelli R, Mokini V, Scanderbeg AC, Dallapiccola B. Brachycephalosyndactyly with ptosis, cataract, colobomas, and linear areas of skin depigmentation. Clin Dysmorphol 1999 Jan;8(1):73-5	A male patient with brachycephalosyndactyly syndrome associated with ocular and skin anomalies is reported and it is suggested that this patient has a previously undescribed disorder.
87	Moog U, P Maroteaux, C T R M Schrander-Stumpel, A van Ooij, J J P Schrander, J P Fryns. Two sibs with an unusual pattern of skeletal malformations resembling osteogenesis imperfecta: a new type of skeletal dysplasia? J Med Genet 1999;36(11):856-858	We report a 6 year old boy with multiple fractures owing to bilateral, peculiar, wave-like defects of the tibial corticaliswith alternative hyperostosis and thinning. Furthermore, he hadWormian bones of the skull, dentinogenesis imperfecta, and a distinctfacial phenotype with hypertelorism and periorbital fullness.Collagen studies showed normal results. His sister, aged 2 years,showed the same facial phenotype and dental abnormalities as wellas Wormian bones, but no radiographical abnormalities of the tubularbones so far. The mother also had dentine abnormalities but noskeletal abnormalities on x ray. This entity is probably the sameas that described in a sporadic case by Suarez and Stickler in1974.В In spite of the considerable overlap with osteogenesis imperfecta(bone fragility, Wormian bones, and dentinogenesis imperfecta),we believe this disorder to be a different entity, in particularbecause of the unique cortical defects, missing osteopenia, andnormal results of collagenstudies.
88	Mori Pier Giorgio, Manuela Priolo, Margherita Lerone, Mirella Pasino, Francesco Caroli, Roberto Cusano, Marco Seri, Margherita Cirillo Silengo. Congenital hypoplastic anaemia in a patient with a new multiple congenital anomalies-mental retardation syndrome. Am. J. Med. Genet. 87(1):36-39, 1999	We report on a girl with congenital hypoplastic anaemia, coarse face, generalized hypertrichosis with scalp hypotrichosis, short fifth finger, hypoplastic toenails, and mental retardation. A sister of the proposita, who died at the age of 1 year, had severe congenital anaemia, hypoplastic fingernails, low birth weight, failure to thrive, and repeated upper respiratory tract infections. Based on family history, we suspect that hypoplastic anaemia and the same multiple congenital anomalies-mental retardation syndrome (MCA/MR) were also present in this sister. To the best of our knowledge, this patient represents the first report of congenital hypoplastic anaemia and such a complex MCA/MR syndrome, probably inherited as an autosomal recessive trait.
89	Mubashir MA, Sabry MA, Farah S, Haseeb N, Quasrawi B, al-Busairi W, al-Dabbous R, al-Awadi SA, Farag TI. New syndromic entity of situs inversus totalis. Clin Dysmorphol 1999 Jan;8(1):23-7	A 22-year-old Bedouin female with MCA/MR has been recently ascertained. She showed profound mental retardation, proportionate short stature, facial dysmorphism, spastic quadreparesis, bilateral taliper equinovarus, brachydactyly, situs inversus totalis, and MRI findings of cerebellar/midbrain migration defects. The described phenotype represents a new syndromic situs inversus with a characteristic Facio-Cerebro-Skeleto-Cardiac phenotype
90	New MI, Nimkarn S, Brandon DD, Cunningham-Rundles S, Wilson RC, Newfield RS, Vandermeulen J, Barron N, Russo C, Loriaux DL, O'Malley B. Resistance to several steroids in two sisters. J Clin Endocrinol Metab 1999 Dec;84(12):4454-64	A 14-yr-old native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of apparent mineralocorticoid excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens, but no resistance to vitamin D or thyroid hormones. She lacked Cushingoid features despite significantly high cortisol levels. Menstruation was regular, and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly due to a coactivator defect.
91	Nisbet DL, Chitty LS, Rodeck CH, Scott RJ. A new syndrome comprising vertebral anomalies and multicystic kidneys.Clin Dysmorphol 1999 Jul;8(3):173-8	We report a dichorionic twin pregnancy in which both fetuses were affected by a similar pattern of multiple abnormalities. The afrocaribbean parents had a history of infertility, and the pregnancy was conceived using in vitro fertilisation with donor sperm. The features seen in the fetuses do not fit any previously described disorder well. We discuss the differential diagnoses and suggest that this may be an autosomal recessive disorder which has not been previously described.
92	Nishiki M, Murakami Y, Yamane Y, Kato Y. Steroid-sensitive nephrotic syndrome, sarcoidosis and thyroiditis--a new syndrome? Nephrol Dial Transplant 1999 Aug;14(8):2008-10	No abstract available
93	Nishimura G, Kimizuka M, Shiro R, Nii E, Nishiyama M, Kawano T, Kaku T, Kawada Y. Ischio-spinal dysostosis: a previously unrecognised combination of malformations. Pediatr Radiol 1999 Mar;29(3):212-7	BACKGROUND: Ischial hypoplasia is an extremely rare malformation, both as an isolated anomaly and as a syndromic constituent. OBJECTIVE: To elucidate the clinical and radiological characteristics in five patients with the combination of ischial hypoplasia and spinal malformations. MATERIALS AND METHODS: The clinical records and radiographs of two females and three males, ranging in age from 3 months to 38 years, were evaluated. RESULTS: Ossification defects of the ischial rami were symmetrical and total in four patients, whereas the right ischial ramus was partly ossified in the other patient. All patients possessed multiple segmental defects of the spine, with rib anomalies of varying severity. One patient characteristically showed multiple rib gaps, resulting in respiratory distress. Severe anomalies of the cervical spine were evident in two patients. Four patients exhibited lumbosacral hypoplasia, which ultimately led to cauda equina syndrome in three older patients. One patient had mild facial dysmorphism and another had a diversity of anomalies, including ichthyosiform skin changes. Four patients were sporadic cases, whereas the other patient was born to consanguineous parents. CONCLUSIONS: The combination of anomalies in these patients constitutes a recognisable pattern of malformations but may represent a heterogeneous group of disorders.
94	Nishimura Gen, Nobuhiko Haga, Katsuhiko Aoki, Minoru Hamazaki, Kazuhiko Taniguchi, Tsutomu Iwaya. New brittle bone disorder: Report of a family with six affected individuals. Am. J. Med. Genet. 84(4):320-329, 1999	We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications.
95	Nowaczyk M.J.M, Sutcliffe T.L. Blepharophimosis, minor facial anomalies, genital anomalies, and mental retardation: Report of two sibs with a unique syndrome. Am. J. Med. Genet. 87:78-81, 1999.	We report on two sibs, a 2.5-year-old girl and a 10-month-old boy, with a hitherto unreported combination of congenital anomalies: blepharophimosis, ptosis, midface hypoplasia, abnormal palate, low anterior and posterior hairlines, displaced hair whorl, apparently low-set and abnormally shaped ears, trigonocephaly, dental anomalies, laryngomalacia, sensorineural hearing loss, genital anomalies, hypotonia, and mental retardation. The occurrence of a similar pattern of anomalies in two sibs of opposite sex suggests autosomal recessive inheritance. To our knowledge, this combination of anomalies has not been reported previously, and thus we propose it to be a formal genesis syndrome.
96	Oguzkurt P, Tanyel FC, Hicsonmez A. Vaginal atresia and Bardet-Biedl syndrome association: a component or a distinct entity? J Pediatr Surg 1999 Mar;34(3):504-6	Bardet-Biedl syndrome is an autosomal recessive disorder. It is characterized by cardinal anomalies including retinal dystrophy, digital malformations, mental retardation, obesity, and hypogonadism. Recently, renal anomalies also are mentioned among the cardinal signs. Although association of genital anomalies among affected boys are well known, the association of vaginal atresia and other structural genital anomalies are not mentioned among the less-common manifestations of Bardet-Biedl syndrome in girls. Two girls with Bardet-Biedl syndrome presented with hematometrocolpos in the preadolescent period and vaginal atresia was diagnosed. After surgical treatment and extended hospitalization, uncontrolled sepsis resulted in progressive renal failure and death of both patients. Vaginal atresia is often delayed or missed in the early childhood period. In girls with Bardet-Biedl syndrome, vaginal atresia or other structural genital anomalies should be evaluated more systematically during the initial diagnosis of the syndrome. In infancy, the evaluation of a child with vaginal atresia also should include the differential diagnosis of Bardet-Biedl syndrome. Vaginal atresia may either form a component of the syndrome, or girls who present with vaginal atresia in addition to other components of Bardet-Biedl syndrome might form a distinct entity.
97	Orrico A; Hayek G; Burroni L. Autosomal recessive syndrome of growth and mental retardation, seizures, retinal abnormalities, and osteodysplasia with similarity to the Gurrieri syndrome. Am J Med Genet, 82(1):84-7 1999	We report on two sibs, brother and sister, with a multiple congenital anomaly/mental retardation syndrome consisting of severe growth and mental retardation, seizures, retinal abnormalities, osteodysplasia, brachydactyly, prognathism, and dental malocclusion. These clinical findings were present in both patients and seem to be consistent with the phenotype of the Gurrieri syndrome. The new features described in these sibs could expand the clinical spectrum of the Gurrieri syndrome and confirm the existence of this rare autosomal recessive condition.
98	Peiffer Andy, Nanda Singh, Mark Leppert, William B. Dobyns, John C. Carey. Microcephaly with simplified gyral pattern in six related children. Am. J. Med. Genet. 84:137-144, 1999	We describe clinical and neurophysiological findings in six related children with congenital microcephaly, seizures that began within the first 2-4 months of life, and severe mental retardation (MR). These affected children (five girls and one boy), born to two women who are half-sisters, inherited the disease as an autosomal recessive trait. Physical examination of these children did not show any of the anomalies in the known cortical malformation syndromes such as lissencephaly types I and II. Neuroradiological studies in these children documented microcephaly and a simplified gyral pattern with no pachygyria. Chromosomal analysis showed neither karyotypic abnormalities nor a microdeletion at 17p13.3, site of the lissencephaly type I gene locus (LIS1). Genetic studies failed to show linkage of this family to LIS1, LIS2(a region on chromosome 2p homologous to LIS1), or MCPH1 (a locus for primary autosomal recessive microcephaly). The unique clinical and genetic findings in this family suggest that these children may be affected by an as-of-yet unmapped neuronal proliferation disorder.
99	Percin EF, Percin S. A new combination: short stature, congenital unilateral absence of the fibula, oligodactyly and trigonocephaly. Clin Dysmorphol 1999 Jan;8(1):67-8 (letter)	No abstract available.
100	Phadke SR, Pahi J, Pandey A, Agarwal SS. Oral-facial-digital syndrome with acromelic short stature: a new variant--overlap with Ellis Van Creveld syndrome. Clin Dysmorphol 1999 Jul;8(3):185-8	The Oral-Facial-Digital syndromes (OFDS) are a heterogeneous group of disorders having common oral, facial, and digital malformations. Here, we report a consanguineous family with a new variety of OFDS associated with acromelic short stature and genu valgum; the features overlapping with Ellis Van Creveld syndrome. One of the sibs has urinary incontinence and growth hormone deficiency, which has not been reported earlier in any type of OFDS in the literature.
101	Pradhan M, Shubha R. Phadke, S. Jain, S. S. Agarwal. Pachygyria/hypogenitalism: A monogenic syndrome. Am. J. Med. Genet. 87:254-257, 1999	We describe the clinical and neuroimaging findings of two severely retarded boys born to consanguineous parents. This appears to be a monogenic condition of abnormal neuronal migration associated with hypogenitalism. Reports of other monogenic syndromes of neuronal migration abnormalities are reviewed.
102	Rauch Anita, Karla A. Feindt, Claire O. Leonard, Joel A. Thompson, Robert O. Hoffman, Donnell J. Creel, John M. Opitz. Previously apparently undescribed autosomal recessive MCA/MR syndrome with light fixation, retinal cone dystrophy, and seizures: The M syndrome. Am. J. Med. Genet. 82(2):194-198, 1999	We report on two sisters from healthy families with a syndrome of severe developmental delay, ataxia, impaired social interaction, a seizure disorder with early onset but without epileptiform electroencephalogram changes, and a striking light-fixating behavior which was associated with retinal cone dystrophy. Additionally, they have minor anomalies including peripheral iris hypoplasia, bluish sclerae, mild anteversion of nostrils, micrognathia, ear anomalies, broad halluces and thumbs, hypoplastic toenails, short perineal body, Mongolian spots, mild hirsutism, hypoplastic ridges in the hypothenar area, and distal axial triradii. Growth and general health are normal in both, but one also had tetralogy of Fallot and vesicoureteral reflux. Because this condition appears to be previously undescribed we postulate a new autosomal recessive disorder with light-fixating behavior and retinal cone dystrophy as leading symptom.
103	Renouil M, Fourmaintraux A, Cartault F, Rodriguez D, Razafinarivo-Schoreitz S, Chaurand G, Wendling C, Bangui A, Ponsot G. [Severe anorexia in infants in Reunion: a new autosomal recessive disease]? Arch Pediatr 1999 Jul;6(7):725-34	BACKGROUND: Infantile anorexia is usually considered as a psychogenic disorder with benign prognosis. However, unusually severe characteristics of infantile anorexia, seen in the south of the island, seem to us in favor of a new metabolic etiology. POPULATION AND METHODS: Among 38 known cases, we retrospectively studied the best documented observations of 24 children admitted over the last 25 years to our institution. RESULTS: The sex ratio was ten females and 14 males. Twenty-three of the 24 infants lived in formerly isolated localities of the island where other hereditary diseases have been observed with an unusually high frequency. The family pedigrees favoured an autosomal recessive heredity. Severe anorexia, accompanied by irrepressible vomiting (91%), appeared at the age of 8.5 months +/- 3.5. Parenteral (54.2%) or enteral (54.2%) feeding was necessary but did not always avoid death, which occurred in 45.8% of the cases at the age of 24 months +/- 3.5. All of the children which survived had neurological disorders (pyramidal syndrome, ataxia, laryngeal palsy, mental retardation, seizures) which occurred sometimes at an early stage. The investigations did not allow the identification of any known cause. DISCUSSION: The elevated level of lactic acid in the cerebral spinal fluid seemed to indicate a possible mitochondrial disorder, eventually a mutation of an autosomal gene of the pyruvate dehydrogenase complex because of the normal lactate/pyruvate ratio, but enzymatic activities were normal. The cerebral MRI showed features of leukodystrophy. On the other hand, the elevated level of plasma serotonin seemed to indicate a disorder of the serotonin metabolism, for which an animal model exists. CONCLUSION: We propose to name this new syndrome by the acronym 'RAVINE' which associates Reunion, Anorexia, Vomiting which is Irrepressible, and Neurological signs. Linkage study might allow the localization and isolation of a gene and allow one to start understanding the biological mechanism which we suspect to be an hereditary neurobiological eating disorder.
104	Reyniers E, Van Bogaert P, Peeters N, Vits L, Pauly F, Fransen E, Van Regemorter N, Kooy RF. A New Neurological Syndrome with Mental Retardation, Choreoathetosis, and Abnormal Behavior Maps to Chromosome Xp11. Am J Hum Genet 1999 Nov;65(5):1406-1412	Choreoathetosis is a major clinical feature in only a small number of hereditary neurological disorders. We define a new X-linked syndrome with a unique clinical picture characterized by mild mental retardation, choreoathetosis, and abnormal behavior. We mapped the disease in a four-generation pedigree to chromosome Xp11 by linkage analysis and defined a candidate region containing a number of genes possibly involved in neuronal signaling, including a potassium channel gene and a neuronal G protein-coupled receptor.
105	Robertson SP, Bankier A. Sotos syndrome and cutis laxa. J Med Genet 1999 Jan;36(1):51-6	Characteristics suggestive of connective tissue dysfunction have been described in Sotos syndrome and include joint hyperextensibility, pes planus, and a high arched palate. A variety of cutis laxa syndromes have also been described, some of them exhibiting mental retardation, but no reports have drawn an association with overgrowth or abnormal facies characteristic of Sotos syndrome. We report three patients with the anthropometric and dysmorphological appearance of classical Sotos syndrome in association with redundant skin folds, joint hypermobility, and, in two of the three, vesicoureteric reflux suggestive of a coexisting connective tissue disorder. All of the patients had a normal bone age suggesting that Sotos syndrome in its classically described form was not present and that this entity possibly reflects a related, perhaps allelic, condition.
106	Roifman CM. Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. Clin Genet 1999 Feb;55(2):103-9	The clinical and laboratory combination of recurrent infections due to antibody deficiency, spondyloepiphyseal dysplasia, growth retardation and retinal dystrophy is novel. Four patients with strikingly similar phenotypes from three different families of diverse genetic backgrounds are described, suggesting a similar underlying genotype. Increased awareness of this syndrome will hopefully lead to the description of a larger number of affected individuals, which ultimately might be critical for its genetic characterization.
107	Seri M, Cusano R, Forabosco P, Cinti R, Caroli F, Picco P, Bini R, Morra VB, De Michele G, Lerone M, Silengo M, Pela I, Borrone C, Romeo G, Devoto M. Genetic mapping to 10q23.3-q24.2, in a large italian pedigree, of a new syndrome showing bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy. Am J Hum Genet 1999 Feb;64(2):586-93	We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis. In three subsequent generations, 13 affected individuals presented with bilateral cataracts, gastroesophageal reflux with persistent vomiting, and spastic paraparesis with amyotrophy. Bilateral cataracts occurred in all affected individuals, with the exception of one patient who presented with a chorioretinal dystrophy, whereas clinical signs of spastic paraparesis showed a variable expressivity. Using a genomewide mapping approach, we mapped the disorder to the long arm of chromosome 10 on band q23.3-q24.2, in a 12-cM chromosomal region where additional neurologic disorders have been localized. The spectrum of phenotypic manifestations in this family is reminiscent of a smaller pedigree, reported recently, confirming the possibility of a new syndrome. Finally, the anticipation of symptoms suggests that an unstable trinucleotide repeat may be responsible for the condition.
108	Service FJ, Natt N, Thompson GB, Grant CS, van Heerden JA, Andrews JC, Lorenz E, Terzic A, Lloyd RV. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J Clin Endocrinol Metab 1999 May;84(5):1582-9	In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic beta-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium channel responsible for glucose-induced insulin secretion. Four patients who underwent gradient-guided partial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has had brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in the absence of insulinoma may constitute a new syndrome of postprandial hypoglycemia from diffuse beta-cell hyperfunction.
109	Shrimpton AE, Daly KM, Hoo JJ. Mapping of a gene (MRXS9) for X-linked mental retardation, microcephaly, and variably short stature to Xq12-q21.31. Am J Med Genet 1999 May 28;84(3):293-9	Three boys from two families were identified as having a syndrome of X-linked mental retardation (XLMR) with microcephaly and short stature, clinically resembling Renpenning syndrome but with normal size of testicles in affected men. When the effort to map the gene for the above condition was initiated, it was realized that the two families were actually related to each other. Over 50 polymorphic markers of known locations along the X chromosome were scored in this family in a study to map the disease gene. Nine affected and four unaffected males were genotyped to produce a maximum LOD score of 4.42 at zero recombination with markers in proximal Xq. The results indicate that the gene responsible for this disorder is located in the cytogenetic Xq12 to Xq21.31 interval of the X chromosome within a section of chromosome of about 17 cM between the AR and DXS1217 loci over some 25 mb. Since the gene for the X-linked mental retardation from the original Saskatchewan family described by Renpenning [Renpenning et al., 1962: Can Med Assoc J 87:954-956; Fox and Gerrard, 1980: Am J Med Genet 7:491-495] was recently mapped to a different nonoverlapping region [Stevenson et al., 1998: Am J Hum Genet 62:1092-1101] this would appear to be a separate disorder.
110	Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, Heineman-de Boer JA, Ropers HH, Mariman EC. X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3. Am J Med Genet 1999 Jul;85(3):216-220	A family is described in which X-linked mild to borderline mental retardation (MR) is associated with cleft lip/palate. Linkage analysis showed a maximum LOD score of Z=2.78 at straight theta=0.0 for the DXS441 locus with flanking markers DXS337 and DXS990, defining the region Xp11.3-q21.3 with a linkage interval of 25 cM.
111	Slaney SF, Chong WK, Winter RM. A new syndrome of short stature, distinctive facial features and periventricular grey matter heterotopia. Clin Dysmorphol 1999 Jan;8(1):5-9	We report on a male infant with distinctive facial features, short stature and rhizomelic upper limb shortening. His MRI brain scan showed abnormal ventricular architecture and bilateral periventricular nodular grey matter heterotopia (BPNH). This child represents an apparently new dysmorphic syndrome.
112	Slaney SF, Goodman FR, Eilers-Walsman BL, Hall BD, Williams DK, Young ID, Hayward RD, Jones BM, Christianson AL, Winter RM. Acromelic frontonasal dysostosis.Am J Med Genet 1999 Mar 12;83(2):109-16	We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.
113	Slaney SF, Hall CM, Atherton DJ, Winter RM. A new syndrome of spondyloepimetaphyseal dysplasia, eczema and hypogammaglobulinaemia. Clin Dysmorphol 1999 Apr;8(2):79-85	We describe a female infant with a combination of very short stature, severe eczema and IgG deficiency causing recurrent infections in infancy. The radiological features of this condition are presented in the neonatal period, at the age of 5 months and at 2 years and 6 months. We propose that this condition is a previously undescribed type of spondyloepimetaphyseal dysplasia.
114	Slaney SF, Sprigg A, Davies NP, Hall CM. Lethal micromelic short-rib skeletal dysplasia with triangular-shaped humerus. Pediatr Radiol 1999 Nov;29(11):835-7	We report two brothers with a new type of lethal, micromelic, short-rib, skeletal dysplasia characterised by short limbs with distinctive triangular-shaped humeri. This condition is most likely caused by either an autosomal recessive or X-linked recessive gene.
115	Slavotinek A., and Clayton-Smith J. A girl with ectodermal dysplasia, choanal atresia and polysyndactyly. Clin Dysmorphol., 1999, 8(4):287-289	No abstract available.
116	Slee Jennie, Geoffrey Lam, Ian Walpole. Syndrome of microcephaly, microphthalmia, cataracts, and intracranial calcification. Am. J. Med. Genet. 84:330-333, 1999	We present two sisters with microcephaly, developmental delay, marked microphthalmia, congenital cataracts, cerebral and cerebellar hypoplasia, and intracranial calcification. No evidence of intrauterine infection was found. There have been previous reports of microcephaly, intracranial calcification, and an intrauterine infection-like autosomal recessive condition, but the sibs in this report appear to represent a more severe form of such a condition or a previously undescribed entity.
117	Stibler H, Gylje H, Uller A. A neurodystrophic syndrome resembling carbohydrate-deficient glycoprotein syndrome type III.Neuropediatrics 1999 Apr;30(2):90-2	A 10-month old girl is described with a serum transferrin isoform abnormality of the same kind as in two previously reported girls with carbohydrate-deficient glycoprotein syndrome type III. This patient presented with joint abnormalities and rapidly developing hypsarrythmia, hypotonia, psychomotor delay and growth retardation. Fingers, toes, nails and local skin were dysmorphic. She had pale optic discs, thoracic syringomyelia and frontal lobe atrophy at three months. The CDT value in serum was greatly elevated. Several carbohydrate-deficient isoforms were found in transferrin (four), alpha1-antitrypsin (three), antithrombin (two) and thyroxine-binding globulin (four). Mutations in the CDGS 1-gene were excluded. The CDGS III glycoprotein abnormality most pobably represents a distinct disorder of glycoprotein metabolism, and