Congenital ichthyosis in Prader–Willi syndrome associated with maternal chromosome 15 uniparental disomy: Case report and review of autosomal recessive conditions unmasked by UPD

Karthik Muthusamy, Erica L. Macke, Eric W. Klee, Peter J. Tebben, Jennifer L. Hand, Linda Hasadsri, Cherisse A. Marcou, Lisa A. Schimmenti

Research output: Contribution to journalArticle

Abstract

Prader–Willi syndrome (PWS) is a prototypic genetic condition related to imprinting. Causative mechanisms include paternal 15q11-q13 deletion, maternal chromosome 15 uniparental disomy (UPD15), Prader–Willi Syndrome/Angelman Syndrome (PWS/AS) critical region imprinting defects, and complex chromosomal rearrangements. Maternal UPD15-related PWS poses risks of concomitant autosomal recessive (AR) disorders when the mother carries a pathogenic variant in one of the genes on chromosome 15 associated with autosomal recessive inherited disease. Co-occurrence of autosomal recessive conditions in the setting of UPD leads to increased complexity of the clinical phenotype, and may delay the diagnosis of PWS. We report a patient with PWS and associated congenital ichthyosis due to maternal UPD15, and a homozygous novel pathogenic variant in ceramide synthase 3 (CERS3). We also review the literature of associated disorders reported in the setting of maternal UPD15-related PWS and provide a summary of the previously described CERS3 variants. This represents the second case of autosomal recessive congenital ichthyosis (ARCI) in the setting of PWS and UPD15. There needs to be a high index of suspicion of this genetic mechanism when there is unexpected phenotype or evolution of the clinical course in a patient with PWS.

Original languageEnglish (US)
Pages (from-to)2442-2449
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume182
Issue number10
DOIs
StateAccepted/In press - 2020

Keywords

  • CERS3-related ichthyosis
  • Prader–Willi syndrome
  • autosomal recessive disorders
  • uniparental disomy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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