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Focal dermal hypoplasia (FDH; MIM 305600), also known as Goltz syndrome or Goltz-Gorlin syndrome is an X-linked dominant disorder caused by mutations in the PORCN gene. PORCN encodes a putative O-acyltransferase involved in palmitoylation of Wnt signaling proteins which play important roles in embryonic development. Individuals with PORCN mutations have defects in ectodermal and mesodermal tissues. The skin, eyes, skeleton and teeth are primarily affected in patients with FDH. Typical skin findings include linear or reticular hyperpigmentation or hypopigmentation, patchy skin atrophy, hairlessness, deposition of subcutaneous fat into the dermis, papillomas of the mucosa and nail dysplasia. Eye findings include coloboma, microphthalmia, aniridia, unilateral anophthalmia, corneal opacities and cataracts. Skeletal findings include asymmetrical skeletal defects, syndactyly, brachydactyly, oligodactyly, ectrodactyly and polydactyly. Additional findings include microcephaly, cleft lip/palate, facial asymmetry, short stature, diastasis pubis and osteopathia striata. Abnormalities of the teeth include, hypodontia, oligodontia, hypoplasia of the enamel, delayed eruption and malocclusion. Kidney or urinary tract malformations including horseshoe kidney, bilateral kidney hypoplasia, hydronephrosis and bifid ureter have also been documented. Mental retardation occurs in about 15% of patients with FDH. Females represent about 90% of individuals with FDH. About 95% of the female cases and almost all male cases appear to be de novo. Most females with FDH display extreme skewing of X-chromosome inactivation. Some females and the majority of males have postzygotic de novo mutations resulting in functional mosaicism. Some male cases may be explained by a 47, XXY karyotype. The phenotype seems to be dependent, to some extent, on the degree of functional mosaicism. Because of the mosaicism, DNA sequence analysis of any one cell type may not be highly sensitive for mutation detection. The prevalence of FDH is not known.