title: Phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals.
abstract: 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.
authors: Bret
authors: B
authors: Bostwick
authors: Ping
authors: P
authors: Fang
authors: Ankita
authors: A
authors: Patel
authors: V Reid
authors: VR
authors: Sutton
mesh_terms: D000217:Acyltransferases; D000483:Alleles; D019943:Amino Acid Substitution; D015331:Cohort Studies; D019066:Facies; D005260:Female; D005489:Focal Dermal Hypoplasia / Q000175:diagnosis* / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D012867:Skin / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D000217:Acyltransferases; C491188:PORCN protein, human
keywords: Goltz syndrome; PORCN; adipose nodules; aplasia cutis; clinical diagnostic criteria; deletion; focal dermal hypoplasia; limb defects; mosaic; skin hypoplasia