Cystic kidney dysplasia and polydactyly in 3 sibs with Bardet-Biedl syndrome

Two infants with cystic kidney dysplasia and polydactyly were born to consanguineous parents. One infant died at age 2 months, and the other is currently 3.5 years old. A third pregnancy was terminated following ultrasonographic visualization of large echodense fetal kidneys and polydactyly. Although none had apparent brain anomalies, they were considered to represent the Meckel syndrome. Extinguished responses on electroretinography in our 3.5-year-old patient has led to the diagnosis of Bardet-Biedl syndrome. This observation offers an opportunity to revisit the Bardet-Biedl syndrome and provides further evidence that structural renal abnormalities are characteristic of the syndrome. We wish to alert the clinician to the diagnosis of Bardet-Biedl syndrome in patients with infantile cystic kidney dysplasia. © Wiley-Liss, Inc.     

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.     

Desquamative interstitial pneumonia in sibs

We report on 2 sibs with desquamative interstitial pneumonia. The female died at age 1 7/12 years despite use of prednisolone and methylprednisolone, while the male, now age 3 years, is alive with oxygen support. The occurrence of desquamative interstitial pneumonia in sibs born to normal parents suggests that in some cases the disease is an autosomal-recessive trait. © 1995 Wiley-Liss, Inc.     

Autosomal dominant inheritance in familial angiolipomatosis

A patient with familial angiolipomatosis in whom an autosomal dominant mode of inheritance could be established is described. This patient also had coincidental autosomal dominant polycystic kidney disease.     

Parental consanguinity in two sibs with omodysplasia

Two sibs with omodysplasia were born to phenotypically normal but consanguineous parents. They had severe micromelic dwarfism, facial anomalies, and mental retardation. One had a congenital heart defect. The radiographic findings are typical: hypoplastic distal end of the humerus with radioulnar diastasis. Parental consanguinity and clinical manifestations in 2 sibs suggest autosomal recessive inheritance. © 1994 Wiley-Liss, Inc.     

Syndrome of mental retardation and distal arthrogryposis in sibs

Two sisters presented with a syndrome of characteristic facial anomalies and distal arthrogryposis. The older sister is now 4 years old and is severely mentally retarded. Her sister died of respiratory failure due to hypoplastic lungs shortly after birth. The occurrence of this potentially lethal syndrome in 2 sisters with unaffected parents suggests autosomal recessive inheritance.     

An unknown spondylo-meta-epiphyseal dysplasia in sibs with extreme short stature

In three sibs of Jordanian descent a unique type of severe spondylo-meta-epiphyseal dysplasia results in extreme disproportionate dwarfism. They have a distinct facial appearance with hypotelorism, prognathia, and hypodontia. The limbs are short and the hands and feet stubby. Radiologically, the irregular end plates of the vertebral bodies, the very small and late appearing epiphyseal ossification centres, and the hypoplastic acetabular roofs are most impressive. Histopathologic studies of the growth plate demonstrate characteristic findings with fingerprint-like inclusion bodies in the hypertrophic chondrocytes. This seems to be a distinct, autosomal recessive skeletal dysplasia. © 1996 Wiley-Liss, Inc.     

Cerebro-reno-digital syndrome in two sibs

We describe two sibs with mental retardation, facial anomalies, polydactyly, cerebellar vermis agenesis, and either meningocele or renal cystic dysplasia. The patients' condition appears to belong to a group of cerebro-reno-digital syndromes. Autosomal recessive inheritance is suggested. © 1993 Wiley-Liss, Inc.     

Syndrome of mental retardation,facial anomalies,hypopituitarism, and distal arthrogryposis in sibs

A brother and a sister presented with a malformation syndrome consisting of facial anomalies, distal arthrogryposis with camp-todactyly of fingers and “hammer toes,” severe mental retardation, and hypopituitar-ism. The girl is now 6½ years old and exhibits severe mental retardation. She has abnormal secretion of growth hormone and responded to growth hormone therapy. Her brother was born with the same facial manifestations, distal contractures, and hypopituitarism. He died unexpectedly at age 3 months of no apparent cause. The occurrence of the syndrome in 2 sibs of different sex suggests auto-somal recessive inheritance.     

Leukonychia totalis in two sibs

A sister and a brother, offspring of unaffected consanguineous Arab parents, were found to have leukonychia totalis and flat, wide nails. To our knowledge this is the first report of apparent autosomal recessive transmission of this trait. A parental somatic mutation with gonadal mosaicism may explain the unusual segregation of the trait in this family. © 1993 Wiley-Liss, Inc.     

Dextrocardia with and without situs viscerum inversus in two sibs

We describe two sibs born to consanguineous Sicilian parents who died of severe congenital heart malformation. Both had dextrocardia; however, only the girl had situs viscerum inversus. At necropsy she was found to have a right spleen and right pulmonary isomerism (three lobes in each lung, as commonly found in the asplenia syndrome). This observation, together with other literature reports, suggest that isolated dextrocardia, situs viscerum inversus, and the asplenia-poly-splenia complex may be different end results of a unique dysmorphogenetic process involving the embryonic midline.     

Recurrence of extrahepatic biliary atresia in two half sibs

Extrahepatic biliary atresia (EHBA) usually is a sporadic disorder. Familial cases, including occurrence in sibs and twins, have been reported. We report the first recurrence of EHBA in two half sibs born to a common father and unrelated mothers and suggest the possibility of gonadal mosaicism for a new dominant mutation. © 1992 Wiley-Liss, Inc.     

Pacman dysplasia: Report of two affected sibs

We report on two sib fetuses with radiological and morphological findings similar to those of the recently described lethal skeletal dysplasia termed Pacman dysplasia (McKusick, 167220, Am J Med Genet 1993, 45:558–561). The first fetus, a male, was electively terminated after a routine ultrasound study at 20 weeks showed short-limb dwarfism. The second fetus, a female sib, was also electively terminated after similar, abnormal ultrasound findings were noted at 16 weeks of gestation. Similar to Pacman dysplasia, the radiographic appearance was characterized by under-mineralized bone, stippling, rhizomelic and mesomelic shortness, platyspondyly, and a short, broad pelvis. The metaphyses were dense, but the diaphyseal cortices were thin with undermodeled long bones, and there was a deficient trabecular pattern suggesting marrow replacement. Chondro-osseous structure was characterized by deficient trabecular bone formation, a fibrous marrow, and numerous, large, multinucleated osteoclasts lining the endosteal surfaces of the metaphyseal bone. The occurrence of this dysplasia in sibs of differing sex suggests autosomal recessive inheritance. Am. J. Med. Genet. 77:272–276, 1998. © 1998 Wiley-Liss, Inc.     

Widespread aplasia cutis congenita in sibs with PLEC1 and ITGB4 variants

Aplasia cutis congenita (ACC) is a heterogeneous group of disorders characterized by localized or widespread absence of skin. ACC can occur isolated or as part of a syndrome. Here we report two consanguineous families, each with two affected offspring. Affected individuals showed widespread ACC while the skin in between had a normal appearance. Ears and nose of the four patients were underdeveloped, otherwise there were no unusual physical characteristics and no internal organ anomalies. “Whole” exome sequencing (WES) of the mother of Family 1 yielded a pathogenic heterozygote variant in ITGB4. The father and healthy offspring were heterozygous for the same variant. WES of the mother of Family 2 yielded a variant in PLEC1. The father and grandmother, who had a history of two offspring with fatal ACC, were heterozygous for the same variant. PLEC1 and ITGB4 have both been previously been reported in association with ACC. We compare findings in earlier reported individuals with variants in ITGB4 and PLEC1, and provide a short summary of other entities going along with ACC.     

Diffuse cystic renal dysplasia: Nonsyndromal familial case

We report on a family in which three individuals, a male and two females were affected with nonsyndromal diffuse cystic dysplasia of the kidneys. The parents had no renal abnormality. The occurrence of diffuse cystic dysplasia in three sibs born to normal parents suggests autosomal recessive inheritance. © 1996 Wiley-Liss, Inc.