Phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Vol. 172C; no. 1; pp. 9 - 20
• Main Authors: Bostwick, Bret, Fang, Ping, Patel, Ankita, Sutton, V. Reid
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2016; Wiley Subscription Services, Inc
• Subjects: Abnormalities; Acyltransferases; adipose nodules; Alleles; Amino Acid Substitution; aplasia cutis; Apnea; Chromosome deletion; clinical diagnostic criteria; Cohort Studies; Criteria; deletion; Diagnostic systems; DNA microarrays; Ectoderm; Facies; Feet; Female; Focal dermal hypoplasia; Focal Dermal Hypoplasia - diagnosis; Focal Dermal Hypoplasia - genetics; Genetic Association Studies; Genetics; Genotype; Goltz syndrome; Hereditary diseases; Humans; Hypoplasia; limb defects; Male; Membrane Proteins - genetics; Mesoderm; Morbidity; mosaic; Mutation; Patients; Phenotype; Physicians; PORCN; Skin; Skin - pathology; skin hypoplasia; Sleep; Sleep disorders; PORCN; aplasia cutis; deletion; limb defects; focal dermal hypoplasia; adipose nodules; mosaic; skin hypoplasia; clinical diagnostic criteria; Goltz syndrome
• ISSN: 1552-4868; 1552-4876; 1552-4876
• DOI: 10.1002/ajmg.c.31473

Focal dermal hypoplasia, or Goltz syndrome, is a highly variable X‐linked dominant disorder with abnormalities in ectoderm and mesoderm derived tissues. Classic clinical features include patchy hypoplastic skin, split hand/foot deformities, and ocular malformations. We aimed to refine the understanding of the phenotypic spectrum and natural history of this disorder and now present multi‐disciplinary clinical description and medical history review for 18 patients with focal dermal hypoplasia. All disease characteristics were analyzed and compiled in aggregate to aid in development of clinical diagnostic criteria. Medical history data unexpectedly revealed that the majority of patients (87%) had undergone tonsillectomy for obstructive sleep apnea, which exposed an important co‐morbidity that is not well described in the literature, but managing physicians should be made aware of. Fifteen of the 18 patients underwent molecular sequencing of PORCN to detect heterozygous or mosaic mutations. Where no mutation was detected, we performed exon‐targeted chromosomal microarray to evaluate for large deletions of the PORCN gene region. We detected a pathogenic genotype in 14 of 15 patients, including one novel chromosomal deletion and four novel PORCN sequence variants. Here, we provide phenotypic summary analysis of 18 patients with focal dermal hypoplasia and propose clinical diagnostic criteria. © 2016 Wiley Periodicals, Inc.