Hydrolethalus Syndrome 2

A number sign (#) is used with this entry because of evidence that hydrolethalus syndrome-2 (HLS2) is caused by homozygous mutation in the KIF7 gene (611254) on chromosome 15q26. One such family has been reported.

Description

Hydrolethalus syndrome is an autosomal recessive embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding. HLS2 is considered a ciliopathy (summary by Putoux et al., 2011).

Acrocallosal syndrome (ACLS; 200990) is an allelic disorder with a less severe phenotype.

For a discussion of genetic heterogeneity of hydrolethalus syndrome, see 236680.

Clinical Features

Putoux et al. (2011) reported a consanguineous Algerian family in which 4 sib fetuses had a lethal developmental disorder consistent with hydrolethalus syndrome. The fetuses ranged in age from 11 to 15 weeks' gestation. Two had anencephaly, 1 of whom had postaxial polydactyly of an upper limb and preaxial polydactyly of both lower limbs. The 2 other fetuses had hydrocephaly, 1 also with arhinencephaly, postaxial polydactyly of the upper limbs, and pre- and postaxial polydactyly of the lower limbs. Two had cleft palate and hallux duplication, and 1 had micrognathia. Neuropathologic examination of 1 fetus showed widened ventricles and midbrain-hindbrain malformation suggestive of the molar tooth sign.

Molecular Genetics

By genomewide linkage analysis followed by candidate gene analysis of a consanguineous Algerian family with hydrolethalus syndrome, Putoux et al. (2011) identified a homozygous deletion in the KIF7 gene (611254.0001) in affected individuals.