Summary

Tibial aplasia-ectrodactyly syndrome is a rare condition characterized by congenital ectrodactylous limb malformations associated with tibial aplasia or hypoplasia. The incidence is estimated to be approximately 1 in 1,000,000 live births. The expression of the phenotype is highly variable and ranges from bilateral aplasia of tibiae and split-hand/split-foot deformity (tetramonodactyly or transverse hemimelia) to the mildest visible manifestation, hypoplastic big toes. Additional malformations may include distal hypoplasia or bifurcation of femora, hypo- or aplasia of ulnae, and minor anomalies such as aplasia of patellae, postaxial and intermediate polydactyly in association with split-hand deformity, and cup-shaped ears. Overlap with the Gollop-Wolfgang syndrome (see this term) has been described. The syndrome is generally inherited in an autosomal dominant manner with reduced penetrance. Autosomal recessive inheritance has also been proposed in some families. Two susceptibility loci at 1q42.2-q43 and 6q14.1 have been identified, leading to the hypothesis that this syndrome fits the model of digenic inheritance.