Co‐occurrence of severe Goltz–Gorlin syndrome and pentalogy of Cantrell – Case report and review of the literature

Abstract

Goltz-Gorlin syndrome is a highly variable disorder affecting many body parts of meso-ectodermal origin. Mutations in X-linked PORCN have been identified in almost all patients with a classical Goltz-Gorlin phenotype. The pentalogy of Cantrell is an infrequently described congenital disorder characterized by the combination of five anomalies: a midline supra-umbilical abdominal wall defect; absent or cleft lower part of the sternum; deficiency of the diaphragmatic pericardium; deficiency of the anterior diaphragm; and congenital heart anomalies. Etiology and pathogenesis are unknown. We report on an infant with findings fitting both Goltz-Gorlin syndrome (sparse hair; anophthalmia; clefting; bifid nose; irregular vermillion of both lips; asymmetrical limb malformations; caudal appendage; linear aplastic skin defects; unilateral hearing loss) and the pentalogy of Cantrell (absent lower sternum; anterior diaphragmatic hernia; ectopia cordis; omphalocele). The clinical diagnosis Goltz-Gorlin syndrome was confirmed molecularly by a point mutation in PORCN (c.727C>T). The presence of molecularly confirmed Goltz-Gorlin syndrome and pentalogy of Cantrell in a single patient has been reported twice before. The present patient confirms that the pentalogy of Cantrell can be caused in some patients by a PORCN mutation. It remains at present uncertain whether this can be explained by the type or localization of the mutation within PORCN, or whether the co-occurrence of the two entities is additionally determined by mutations or polymorphisms in other genes, environmental factors, and/or epigenetic influences.

Goltz syndrome in males: A clinical report of a male patient carrying a novel PORCN variant and a review of the literature

“…Interestingly, all four patients with non‐mosaic PORCN mutations lacked skin manifestations but had other severe symptoms compatible with GS 20, 21. In addition, diaphragm abnormalities were detected in two patients, resembling previously reported cases with pentalogy of Cantrell 18, 22…”

Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia

“…To our knowledge, there are four previous cases reported of PORCN variants in association with syndromic CDH: a female fetus with multiple congenital anomalies including CDH, limb anomalies, microphthalmia and lung anomalies; a female with phenotypic features consistent with FDH and Pentalogy of Cantrell, including an anterior diaphragmatic hernia; and two unrelated female fetuses born to affected mothers who displayed ectopia cordis, diaphragmatic hernia and abdominal wall defects. 5,17,18 Our finding thus adds further support for PORCN variants as a cause of syndromic CDH and not a coincidental association. The novel variant that we report affects the fourth transmembrane domain of the PORCN (porcupine) protein and the putative amino-acid change is predicted to be functionally damaging by four algorithms (SIFT, PolyPhen2, LRT and MutationTaster).…”

The incomplete pentalogy of Cantrell – A case report

“…GGS is a very rare and highly variable disorder affecting tissues of mesodermal and ectodermal origin. Its major manifestations are: (quote from [18]) ''. .…”

“…Smigiel et al [18,19] describes a female neonate with coexistence of Goltz-Gorlin syndrome (GGS), known also as focal dermal hypoplasia (FDH) and pentalogy of Cantrell. GGS is a very rare and highly variable disorder affecting tissues of mesodermal and ectodermal origin.…”