De Barsy syndrome: report of a case, literature review, and elastin gene expression studies of the skin.

Several "progeroid" syndromes have now been identified. The De Barsy syndrome is an autosomal recessive syndrome of dwarfism, mental deficiency, an "aged" appearance at birth, abnormal elastic fibers on skin biopsy, and lax skin, large helices, eye abnormalities, lax joints, hypotonia, and athetoid posturing. We report one case and review 11 cases from the literature. To understand the abnormal appearance of the elastic fibers on biopsy, we performed elastin gene expression studies on fibroblasts cultured from our patient's skin. Molecular hybridization studies revealed reduced elastin mRNA steady-state levels as compared with age matched control individuals. Assuming normal rates of mRNA translation, reduced elastin synthesis would occur. Diminished dermal elastin content could explain the altered cutaneous elasticity, decreased elastic fibers in the skin, and many clinical manifestations of individuals with this condition.     

The wrinkly skin syndrome: a report of a case and review of the literature

A 2 1/2-year-old boy born of Jewish Moroccan parents is reported with physical findings of wrinkled skin on the dorsum of the hands and feet, with poor skin elasticity, syndactyly, mild kyphosis and poor muscle tone, the diagnosis being the wrinkly skin syndrome. All reported cases of this heritable disorder of connective tissue are reviewed and discussed in terms of genetics, ethnic clustering and differential diagnosis.     

Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome

De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS.     

The Meckel syndrome: Report of two Japanese sibs and a review of literature

Two Japanese sibs with the Meckel syndrome are reported. Both babies showed the classical triad of this condition: occipital encephalocele, cystic kidneys, and postaxial polydactyly of all four limbs. The diagnostic criteria and differential diagnosis were reviewed. © 1996 Wiley-Liss, Inc.     

Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: Report of a new family and review of the literature

Treacher Collins syndrome (TCS) is a frequent cause of mandibulofacial dysostosis. To date, TCS‐causing mutations in three genes, namely TCOF1, POLR1D, and POLR1C have been identified. TCS is usually inherited in an autosomal dominant manner, with a high clinical variability and no phenotype–genotype correlation. Up‐to now, five families have been reported with an autosomal recessive mode of inheritance due to mutations in POLR1D or POLR1C. We report here a new family with two sisters affected by mild TCS carrying compound POLR1C heterozygous mutations, and review the literature on mild forms of TCS, autosomal recessive inheritance in this syndrome and POLR1C mutations.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive disorder: Clinical reports and review of the literature

We present 2 new patients with the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), review the literature, and discuss the prenatal diagnosis and treatment. MMIHS, as reported in 43 cases, is usually lethal. Most children die during the first year of life, and only 3 children survived their first year. We report the 6th pair of sibs with the disease. Overall, 17 patients reported have had sibs with MMIHS or the parents were consanguineous; 4 times the parents were first, cousins, confirming that this is an autosomal recessive disorder. The present 2 children, whose parents also were first cousins, were of different sex. They had typical MMIHS with abdominal distension due to pronounced megacystis, hydronephrosis, microcolon, and microileum, involving the distal part of the ileum, malrotation of the gut, and intestinal hypoperistalsis. Neither surgery nor medical treatment was successful and the children died at the age of 19 days and 2¹/2 months, respectively. There is no cure for the disease. However, a new prokinetic drug, Cisapride® might be worth trying in these cases. Prenatal ultrasound diagnosis of MMIHS might be possible.     

Family analysis of Werner's syndrome: A survey of 42 Japanese families with a review of the literature

Forty-two Japanese families, including 80 individuals with Werner's syndrome were studied, confirming that this syndrome is inherited as an autosomal recessive trait. The incidence of malignancy was relatively high in these families and individuals with Werner's syndrome, although the incidence was not so high as was reported previously. HLA typing revealed no significant linkage with Werner's syndrome. The frequency of Werner's syndrome in Japan was estimated using two methods which indicated approximately 300 cases among 100 million people.     

Gerodermia osteodysplastica hereditaria: Report of three affected brothers and literature review

Gerodermia osteodysplastica hereditaria was diagnosed in three Mexican brothers 6, 7, and 8 years old, respectively, who had the distinct facial appearance with sagging cheeks, premature wrinkling of the skin of face, abdomen, and dorsum of hands and feet; malocelusion, span greater than height; hyperextensibility; winging of the scapulae; stooped posture with kyphoscoliosis; protuberant abdomen; and pes planus. Radiologically they had generalized osteoporosis, platyspondily due to multiple compression fractures, pseudoepiphyses of second metacarpals, and dislocated hips. Three other families with a total of 14 affected individuals have been reported. Inter- and intrafamilial variability can be recognized, particularly regarding the tendency to fractures, upper: lower segment ratio abnormalities, and results of skin biopsies, which have shown fragmentation of the elastic fibers in some cases (including the present family) and not in others. Although inheritance was considered to be X-linked recessive in the first reported family, an analysis of that pedigree together with those of the other reported families, including the present one, suggests that gerodermia osteodrysplastica is inherited in an autosomal recessive manner.     

Neu-Laxova syndrome: report of a case from Turkey

Kuseyri F, Bilge I, Bilgiç L, Apak MY. Neu-Laxova syndrome: report of a case from Turkey.
Clin Genet 1993: 43: 267–269. © Munksgaard, 1993
We describe a case of Neu-Laxova syndrome in a newborn female who was born at full-term to consanguineous Turkish parents. The pathological and radiological features are described.     

Complete and partial XY sex reversal associated with terminal deletion of 10q: Report of 2 cases and literature review

We report on a 30-year-old woman with premature aging, immunodeficiency, and other abnormalities. She had many manifestations of the Mulvihill-Smith syndrome, a disorder that has been described in 4 sporadic individuals, ranging in age from 4 to 17 years. The common manifestations include short stature, microcephaly, a senile face with an under-developed lower half, diminished facial subcutaneous fat, multiple pigmented nevi, sensorineural hearing loss, and a low IgG level. Our patient also had severe mental retardation, brachydactyly, severe T cell dysfunction, and suffered from severe verruca vulgaris and a chronic, active Epstein-Barr virus infection. The fact that her parents were first cousins suggests autosomal recessive inheritance of her disorder. Two alternative possibilities were considered: the disorder in the patient represents the Mulvihill-Smith syndrome with immune deficiency as a sign of its advanced stage, or a hitherto undescribed syndrome. © 1993 Wiley-Liss, Inc.     

Heterogeneity of pseudoxanthoma elasticum: delineation of a new form?

Sixty-four patients with pseudoxanthoma elasticum (PXE) were investigated in a nationwide study within South Africa and Zimbabwe. Thirty-nine individuals formed a distinct clinical subgroup. These persons were found exclusively among people of Afrikaner descent, whose origins are mainly derived from Dutch and French-Huguenot stock. This disorder was inherited as an autosomal recessive trait and presented mild to moderate cutaneous and cardiovascular manifestations. However, after the third decade of life severe visual impairment developed and culminated in blindness in 8 people by the age of 50. The cause of the visual defect was progressive extension of angioid streaks into the macula with neovascularization and haemorrhage. Laser therapy may have prevented further bleeding in 4 instances. The severity of ocular involvement contrasted with the mildness of the skin changes, and in this respect the condition seems to differ from previously delineated autosomal recessive forms of PXE.     

Bladder carcinoma in Costello syndrome: Report on a patient born to consanguineous parents and review

We report on a 12-year-old boy with Costello syndrome born to consanguineous (first cousins once removed) parents, supporting the hypothesis of recessive transmission of this syndrome. At age 11 years, the patient developed a bladder carcinoma, a rare pediatric tumor not previously described in Costello syndrome. This suggests that an increased risk of malignancy may be part of this condition. Am. J. Med. Genet. 86:174–179, 1999. © 1999 Wiley-Liss, Inc.     

Report of a case and further delineation of the SHORT syndrome

We describe a boy with the manifestations of the SHORT syndrome: lipoatrophy, delayed speech development, minor facial anomalies, clinodactyly, and short stature. In addition, this boy had deafness, which was not previously reported in the SHORT syndrome.     

Cartilage hair hypoplasia,metaphyseal chondrodysplasia type McKusick: Description of seven patients and review of the literature

We describe 7 cases of cartilage hair hypoplasia (CHH) with emphasis on the clinical and immunological aspects. The literature on CHH is reviewed and symptoms in 63 nonAmish cases are summarized. In this autosomal recessive disorder the immunodeficiency, hair abnormalities, and severity of skeletal involvement show extremely variable expressivity, between and within families. Two of the 3 sib-pairs among our cases demonstrate the great difference in expression within one family. At adult age roentgenological abnormalities can be very mild, or even absent. An impairment in cellmediated immunity is present in all of our cases and seems a consistent manifestation in CHH; however, sometimos it is very subtle and without clinical symptoms.     

Elejalde syndrome: A case report

Elejalde syndrome is a rare condition comprising a high birth weight, swollen globular body, a short neck with redundant skin folds, postaxial polydactyly, omphalocele, enlarged liver and kidneys, and renal dysplasia. The syndrome, also known as acrocephalopolydactylous dysplasia, is thought to be an autosomal recessive trait. We report on a liveborn infant with this condition. Am. J. Med. Genet. 69:406–408, 1997. © 1997 Wiley-Liss, Inc.     

Craniosynostosis and kidney malformation in a case of Hennekam syndrome

Hennekam syndrome is a rare autosomal recessive syndrome which was described for the first time in 1989. Here, we present a girl with intestinal lymphangiectasia, severe lymphedema of limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this syndrome. While the molecular basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its variable clinical expression. © 1995 Wiley-Liss, Inc.     

Craniodigital syndromes: Report of a child with Filippi syndrome and discussion of differential diagnosis

We describe a boy with low birth weight, congenital microcephaly, multiple minor facial anomalies, cleft palate, soft tissue syndactyly of fingers and toes, and moderate to severe mental retardation. Literature review suggested 6 possible diagnoses, including Scott craniodigital syndrome, Chitayat syndrome, Filippi syndrome, Zerres syndrome, Kelly syndrome, and Woods syndrome. Each has as part of the phenotype craniofacial anomalies and soft tissue syndactyly of fingers and toes; and superficially, distinction among the 6 may be difficult. However, based on the phenotype analysis we performed, we conclude that our patient has Filippi syndrome, and thus is the first reported case from the United States. © 1995 Wiley-Liss, Inc.     

Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression

Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression.
Clin Genet 1993: 44: 287–291. © Munksgaard, 1993
Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.