Focal dermal hypoplasia is a multisystem disorder characterized primarily by involvement of the skin, skeletal system, eyes, and face. Skin manifestations present at birth include atrophic and hypoplastic areas of skin; cutis aplasia; fat nodules in the dermis manifesting as soft, yellow-pink cutaneous nodules; and pigmentary changes. Verrucoid papillomas of the skin and mucous membranes may appear later. The nails can be ridged, dysplastic, or hypoplastic; hair can be sparse or absent. Limb malformations include oligo/syndactyly and split hand/foot. Developmental abnormalities of the eye can include anophthalmia/microphthalmia, iris and chorioretinal coloboma, and lacrimal duct abnormalities. Craniofacial findings can include facial asymmetry, notched alae nasi, cleft lip and palate, and pointed chin. Occasional findings include dental anomalies, abdominal wall defects, diaphragmatic hernia, and renal anomalies. Psychomotor development is usually normal; some individuals have cognitive impairment.
Diagnosis is based on clinical findings and molecular genetic testing. PORCN is the only gene in which mutations are known to cause focal dermal hypoplasia.
Focal dermal hypoplasia is inherited in an X-linked dominant manner. Females (90% of affected individuals) are heterozygous or mosaic for mutations in PORCN; live-born affected males (10% of affected individuals) are mosaic for mutations in PORCN. It is presumed that non-mosaic hemizygous males are not viable. Approximately 95% of females with focal dermal hypoplasia have a new gene mutation; approximately 5% inherited the mutation from a parent. The risk that the mutant PORCN allele will be transmitted by an affected female with a heterozygous mutation is 50%; however, most male conceptuses with the mutant PORCN allele are presumed to be spontaneously aborted. Thus, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males. If the affected female has a mosaic mutation, the risk to her female offspring of inheriting the mutation is as high as 50%, depending on the level of mosaicism in her germline. Prenatal molecular genetic testing is possible for pregnancies at increased risk if the disease-causing mutation in the family has been identified.