Fraser syndrome presenting as bilateral renal agenesis in three sibs

A family is reported in which three sibs had bilateral renal agenesis. They shared the features of Fraser syndrome, though only one had crytophthalmos.     

Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome): report of three affected sibs

The Wiedemann-Rautenstrauch syndrome (WRS) (OMIM 264090) is a rare progeroid entity. WRS patients are characterized by premature aging present at birth including pseudohydrocephalus, cranio-facial disproportion, reduced subcutaneous fat, thin skin, rigid and thick joints, and neonatal teeth in some cases. Here we describe three sibs with WRS from unaffected parents and without consanguinity. Our findings support autosomal recessive inheritance in WRS and support the possibility of homozygocity mapping as a good approach to find the causative gene.     

Frequency of the branchio-oto-renal (BOR) syndrome in children with profound hearing loss

Nineteen of 421 white children in Montreal schools for the deaf had preauricular pits. The branchio-oto-renal (BOR syndrome was identified in four of the nine families who agreed to family investigation, including audiograms and intra-venous pyelograms (IVPs), and may have been present in several others. The penetrance of this autosomal dominant syndrome appears to be high. It is estimated that severe renal dysplasia occurs in about 6% of heterozygotes. The presence of a preauricular pit at birth suggests that the child has at least one chance in 200 of severe hearing loss, and this warrants a careful family history, as well as alertness for any signs of hearing impairment. Offspring of affected individuals are eligible for prenatal diagnosis of renal dysplasia.     

Localization of branchio-oto-renal (BOR) syndrome to a 3 Mb region of chromosome 8q

Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Z_max = 3.91 and Z_max = 2.83 respectively at Θ = 0.00. These markers are within 1 cM of one another. Multipoint analysis, involving 7 loci, placed the gene between these markers, with a lod-1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279. © 1994 Wiley-Liss, Inc.     

Osteoporosis-pseudoglioma syndrome: report of three affected sibs and an overview

We report on a sibship with one brother and two MZ twin sisters affected with osteoporosis-pseudoglioma syndrome. An analysis of the present and literature data showed that vitreoretinal dysplasia or phthisis bulbi and X-ray evidence of osteoporosis must be considered minimal diagnostic criteria. Mental retardation, ligamentous laxity, and other reported anomalies are highly variable manifestations in the syndrome. Segregation analysis confirmed autosomal recessive transmission. The geographic origin of reported families suggests a higher gene frequency in Mediterranean countries.     

Fraser syndrome presenting as monozygotic twins with bilateral renal agenesis

Fraser syndrome without cryptophthalmos is described in monozygotic twins concordant for bilateral renal agenesis.     

FamiliaI aggregation in bilateral renal agenesis

Two affected siblings with bilateral renal agenesis are reported. The literature was reviewed and seven families with two affected children each were found. It is suggested that this anomaly may be of genetic etiology and transmitted as an autosomal recessive disorder.     

SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR

Branchio-oto-renal syndrome (BOR) is a clinically heterogeneous autosomal dominant form of syndromic hearing loss characterized by variable hearing impairment, malformations of the pinnae, the presence of branchial arch remnants, and various renal abnormalities. Both EYA1 and SIX1 are expressed in developing otic, branchial and renal tissue. Consistent with this expression pattern, mutations in both genes cause BOR syndrome. Mutations in EYA1 are found in approximately 40% of patients with the BOR phenotype, however, the role of SIX1 is much lower. To date only three different SIX1 mutations have been described in BOR patients. The current screen of 247 BOR families detected five novel SIX1 mutations (c.50T>A, c.218A>C, c.317T>G, c.329G>A, c.334C>T) and one previously reported mutation (c.328C>T) seen in 5 unrelated families. All mutations are within the protein-binding Six domain. Phenotypic variability was high in these BOR families. Seven of the eight known SIX1 mutations are missense and the one in frame deletion is predicted to be functionally similar. The wide phenotypic variability precludes making genotype-phenotype correlations at this time.     

Walker-Warburg syndrome: Report of three affected sibs

Walker-Warburg syndrome (WWS) is a lethal, autosomal recessive disorder characterized by Type II lissencephaly, retinal malformation, cerebellar malformation, and congenital muscular dystrophy. We report on 3 sibs with WWS born to a consanguineous couple. The fetal hydrocephalus associated with this syndrome, while not consistent or necessary for diagnosis, is the key manifestation for its prenatal detection. These sibs illustrate the importance of a careful search for associated malformation(s) in a fetus or newborn infant with hydrocephalus and the potential pitfalls of accurate genetic risk estimation in families of such propositi. © 1994 Wiley-Liss, Inc.     

Bilateral renal agenesis in 2 male sibs born to consanguineous parents.

Two boys with bilateral agenesis of kidneys and ureters were the product of a consanguineous marriage. This family and previous reports of familial bilateral renal agenesis support the supposition that a minor proportion of cases of BRA is caused by the homozygous state of an autosomal recessive gene.     

Prenatal diagnosis of Walker-Warburg syndrome in three sibs

Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on 3 prenatally diagnosed cases of this syndrome born to a consanguineous couple. An ultrasonographic examination showed hydrocephalus at the 27th week of the first pregnancy. Amniocentesis documented a normal male karyotype. The couple opted for termination of the pregnancy but declined an autopsy. Seven months later, hydrocephalus was observed at 20 weeks of the second pregnancy. Termination of pregnancy was performed at the 22nd week. Autopsy of this male fetus showed dilated ventricles, thin cortex, and type II lissencephaly with microscopic evidence of chaotic architecture. Eye examination showed retinal dysplasia. Notwithstanding the lack of demonstrable muscle change, the diagnosis of Walker-Warburg syndrome was made. Ten months later, hydrocephalus was discovered in the third fetus, a female, at 13 weeks of gestation. Termination of pregnancy was performed at 20 weeks. At autopsy, brain, eye, and muscular findings were similar to those of the previous case. In addition, cystic changes and a stenosis of the pyelo-ureteral junction were found in the right kidney. Type II lissencephaly and retinal dysplasia are characteristic of WWS. Muscular dystrophy has been pointed out as an additional abnormality in postnatal cases. By contrast, the lack of demonstrable muscle changes in the fetal period must be emphasized. Those cases illustrate practical problems in the ultrasound and pathologic diagnosis of WWS in the fetal period. Am. J. Med. Genet. 76:107–110, 1998. © 1998 Wiley-Liss, Inc.     

Reproductive risk factors in unilateral and bilateral renal agenesis

ABSTRACT  Renal agenesis (RA) appears to be a multifactorial condition with combined genetic and environmental influences. We performed a retrospective case-control study of reproductive history of 26 isolated RA live births cases referred to Sicilian Registry of Congenital Malformations. A statistical significant association for birth weight if we considered all RA together and for bilateral RA alone, an increasing risk for maternal age only in the bilateral RA subgroup and a male predominance both for unilateral and bilateral RA was found. Our results show that some reproductive risk factors may be associated with RA, moreover differences found between subgroups indicate that some risk factors may be different in unilateral and bilateral RA. The association between reproductive risk factors and RA may reflect pathogenetic interaction between genetic and environmental factors. Nevertheless further studies are needed to clarify these associations and to explore the role of perinatal factors in the etiology of renal agenesis. In fact if prenatal or perinatal risk factors are in a causal chain influencing the risk for developing RA, then these data could have important implications in the prevention or treatment of this condition.