Expanding the phenotype of males with OFD1 pathogenic variants-a case report and literature review

• DOI: 10.1016/j.ejmg.2022.104496
• Publication Date: 2022-04-06T23:29:13Z
• Authors: Balram Gangaram; W. Patrick Devine; Anne Slavotinek
• Keywords: Ciliopathy; Human genetics

Pathogenic variants in the OFD1 gene have been classically associated with Orofaciodigital syndrome type 1 females, a condition previously considered to be X-linked dominant male embryonic lethality. However, an increasing number of males pathogenic who survived beyond neonatal period now reported literature. Although each new report has added ever-broadening spectrum clinical findings seen males, many questions about genotype-phenotype correlations and disease mechanism remain. Herein, we describe 9-year-old child novel hemizygous variant identified by exome sequencing unique combination findings, not reported, including presence both hypothalamic hamartoma molar tooth sign. His features overlap multiple ciliopathy phenotypes, blurring boundaries distinct gene-disease relationships. This case provides further evidence for consideration broad OFD1-relateddisorder affected rather than phenotypes. Additionally, review published cases disorder support inclusion differential diagnosis work up all individuals present primary ciliopathy-type features, regardless their gender. We also highlight current information types pathogenesis explore how these could mechanistically drive some observed phenotypic differences.