A novel type of autosomal recessive syndactyly: clinical and molecular studies in a family of Pakistani origin.

Non-syndromic syndactylies have been classified into five major types (I-V), all showing autosomal dominant mode of inheritance. Later, the classification was extended and three additional variants (VI-VIII) were defined. Type VII, the Cenani-Lenz syndactyly, is the only non-syndromic, autosomal recessive type. It is characterized by fusion of all phalanges with metacarpal synostosis, dislocated and dysplastic carpals and infrequently, radio-ulnar fusion. Here, we present a Pakistani family with a novel non-syndromic autosomal recessive syndactyly manifesting a unique combination of clinical features. In both hands, reduction of certain phalanges is evident. Radiological examination shows synostosis of third and fourth metacarpals bearing single phalanges. The first three toes are webbed, with hypoplastic terminal phalanx in all the toes. Besides Cenani-Lenz syndactyly, the phenotype segregating in our family is the second well-documented autosomal recessive, non-syndromic syndactyly. A phenotype similar to our family was described in a Turkish kindred but was considered to be a homozygous expression of type I syndactyly. Since the clinical features in our family had minimal overlap with syndactyly types I, II, and III, we have performed microsatellite marker screening to look for the cosegregation of this phenotype with any of the known loci for these respective types. We show that the phenotype in our family is not linked to chromosomal regions 2q34-q36, 2q31, and 6q22-q23 encompassing loci for syndactyly types I, II, and III.