Familial acromelic frontonasal dysostosis: autosomal dominant inheritance with reduced penetrance

Acromelic frontonasal dysostosis (AFND) represents a subgroup of patients with frontonasal malformation with limb abnormalities including preaxial polydactyly and tibial hypoplasia. Previous case reports have suggested autosomal recessive inheritance, given parental consanguinity. However, no affected siblings have been described. Longitudinal clinical history is limited as many do not survive the first years of life. The molecular basis of AFND is not known. Previous investigators have proposed that AFND may result from a perturbation in the Sonic Hedgehog pathway. We present clinical and radiographic findings in two unrelated boys, ages 8 and 9 years, with AFND, one of whom has a family history suggesting dominant inheritance. A focused study of genetic marker data and candidate gene mutation analysis in this family is presented.