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 ... 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.
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 ... 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 (MTS).
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.