Abstract

Background: Goltz–Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz–Gorlin syndrome.

Method: A series of 17 patients with Goltz–Gorlin syndrome is reported on, and their phenotype and genotype are described.

Results: In 14 patients (13 females and one male), a PORCN mutation was found. Mutations included nonsense (n = 5), frameshift (n = 2), aberrant splicing (n = 2) and missense (n = 5) mutations. No genotype–phenotype correlation was found. All patients with the classical features of the syndrome had a detectable mutation. In three females with atypical signs, no mutation was found. The male patient had classical features and showed mosaicism for a PORCN nonsense mutation in fibroblasts. Two affected sisters had a mutation not detectable in their parents, supporting germline mosaicism. Their father had undergone radiation for testicular cancer in the past. Two classically affected females had three severely affected female fetuses which all had midline thoracic and abdominal wall defects, resembling the pentalogy of Cantrell and the limb–body wall complex. Thoracic and abdominal wall defects were also present in two surviving patients. PORCN mutations can possibly cause pentalogy of Cantrell and limb–body wall complexes as well. Therefore, particularly in cases with limb defects, it seems useful to search for these.

Conclusions: PORCN mutations can be found in all classically affected cases of Goltz–Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype–phenotype correlation.