Syndactyly Type Haas

Abstract

Syndactyly type Haas is characterized by complete syndactyly affecting all digits of the hand together with polydactyly that includes metacarpals and phalanges. Flexion of the fingers gives the hands a cup-shaped form. The feet may show variable but much milder involvement, with partial cutaneous syndactyly of toes. Autosomal dominant. There is phenotypic overlap with Laurin–Sandrow syndrome. Both conditions show severe, cup-shaped polysyndactyly of the hands. The feet show severe mirror-image polydactyly in Laurin–Sandrow syndrome, which is not a feature of Haas syndactyly. Both conditions result from similar mutations and are likely to represent a phenotypic spectrum. There is similarity to Apert syndrome. Haas-type syndactyly can be caused by mutations in a Sonic hedgehog (SHH) regulatory element (the zone of polarizing activity regulatory sequence, or ZRS) that resides in intron 5 of the LMBR1 gene. Duplications encompassing the ZRS result in the same phenotype. The ZRS is a highly conserved genomic region located in an intron of the LMBR1 gene, some 1 Mb away from SHH. The sequence serves as an enhancer regulating the limb expression of Shh. Deletions of the ZRS result in a loss of Shh expression and thus truncated limbs, whereas mutations and duplications result in a series of conditions, including polydactyly-triphalangeal thumb syndrome, Werner mesomelic dysplasia, Laurin–Sandrow syndrome, and Haas-type syndactyly.