Syndactyly: phenotypes, genetics and current classification

Abstract

Syndactyly is one of the most common hereditary limb malformations depicting the fusion of certain fingers and/or toes. It may occur as an isolated entity or a component of more than 300 syndromic anomalies. Syndactylies exhibit great inter- and intra-familial clinical variability. Even within a subject, phenotype can be unilateral or bilateral and symmetrical or asymmetrical. At least nine non-syndromic syndactylies with additional sub-types have been characterized. Most of the syndactyly types are inherited as autosomal dominant but two autosomal recessive and an X-linked recessive entity have also been described. Whereas the underlying genes/mutations for types II-1, III, IV, V, and VII have been worked out, the etiology and molecular basis of the other syndactyly types remain unknown. In this communication, based on an overview of well-characterized isolated syndactylies, their cardinal phenotypes, inheritance patterns, and clinical and genetic heterogeneities, a 'current classification scheme' is presented. Despite considerable progress in the understanding of syndactyly at clinical and molecular levels, fundamental questions regarding the disturbed developmental mechanisms leading to fused digits, remain to be answered.

Figure 1

Schematic diagrams of syndactyly types (I-a–III). Shaded digits depict cutaneous fusion only, while bony synostosis is represented by black digital elements within the shaded area. The grey digital elements show hypoplastic phalanges or clinodactyly/brachydactyly. The digital elements with amorphous borders symbolize dysplastic bones (adapted from Malik and Grzeschik).

Figure 2

Schematic diagrams of syndactyly types (IV-a–IX).