Abstract

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.

Here we report on a series of 17 Goltz-Gorlin patients, and describe their phenotype and genotype. 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 could be found. All patients with the classical features of the syndrome had a detectable mutation. In three females with atypical signs no mutation could be found. The male patient had classical features and showed a 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. Possibly, PORCN mutations can cause pentalogy of Cantrell and limb-body wall complexes as well, and particularly in cases with limb defects it seems useful to search for these.

We conclude that PORCN mutations can be found in all classically affected cases with Goltz-Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype-phenotype correlation.