A non-mosaic mutation in a male with severe congenital anomalies overlapping focal dermal hypoplasia.

Mutations in the gene cause the X-linked dominant condition focal dermal hypoplasia (FDH). Features of FDH include striated pigmentation of the skin, ocular and skeletal malformations. FDH is generally associated with lethality in non-mosaic males and most of the currently reported male patients show mosaicism due to post-zygotic mutations in the gene. There is only one previous report of a surviving male with an inherited mutation in the gene. Here, we report two male siblings with multiple malformations including skeletal, ocular and renal defects overlapping with FDH. A novel mutation (p.Ser250Phe) was identified in a non-mosaic, hemizygous state in one of the siblings who survived to 8 years of age. The mother is a heterozygous carrier, has a random X-inactivation pattern and is asymptomatic. Findings unusual for FDH include dysplastic clavicles and bilateral Tessier IV facial clefts. This is the second case report of a non-mosaic mutation in a male individual with multiple congenital anomalies. While the pathogenicity of this mutation remains to be further investigated, the survival of a male with a non-mosaic mutation in is suggestive of a functionally mild mutation leading to an X-linked recessive mode of inheritance.