Ectrodactyly with fibular aplasia: a separate entity?

E/FA is the combination of ectrodactyly (split hand/foot malformation, SHFM) and fibular aplasia. It is a rare disorder considered to be inherited in an autosomal dominant fashion with reduced penetrance and variable expression. In order to determine recurrence risks for the two patients we describe, the literature on inheritance of E/FA was carefully reviewed. In our opinion, only two of the eight families previously reported as examples of familial E/FA may fit this judgment. Until mutation analysis of all SHFM genes is possible, the question remains whether these familial cases represent autosomal dominant E/FA, or an allelic variant of an SHFM subtype. Many sporadic patients with presumed E/FA may represent the fibular developmental field defect, which is a non-genetic entity with a low recurrence risk. We therefore suggest that the high recurrence risk associated with autosomal dominant inheritance should not be counselled in patients with E/FA unless their family shows the following characteristics: (1) at least one patient shows typical SHFM combined with fibular aplasia, (2) multiple limbs are affected, and (3) multiple family members are affected in at least two generations.