Kayla Scully¹, Rexson Tse², Sewwandi Francisco¹, Di Milnes³

¹Pathology Queensland (Gold Coast University Hospital), Queensland, Australia
²Forensic Scientific Services (Gold Coast University Hospital), Queensland, Australia
³Genetic Health Queensland, Royal Brisbane Womens Hospital, Queensland, Australia

The oral-facial-digital type 1 (OFD1) protein is a functionally complex protein that is associated with multiple biological functions, namely the formation of cilia and embryological left-right asymmetry. ^[1] Pathological variants in the gene coding for this protein are linked to four potentially phenotypically overlapping OFD1 ciliopathy syndromes with different X-linked inheritance patterns.^[1][2]  As such, diagnosing OFD1-related conditions can be challenging, especially in the perinatal population where specific clinical features have yet to manifest. We present a 24-week male perinate in which multiple anatomical malformations were identified in utero, including severe micrognathia, cleft palate, and right-sided talipes. Further complications during the pregnancy lead to a termination and subsequent perinatal autopsy and advanced genetic testing. Whole exome sequencing found a likely pathological maternally inherited 1bp duplication in OFD1 and autopsy found non-classical features of OFD1 spectrum conditions. Through iterative and collaborative multidisciplinary discussions between pathology and the clinical team, an informative result was able to be curated to guide the mother in subsequent pregnancies. This case highlights the benefit of a collaborative multidisciplinary approach in diagnosing challenging conditions in perinatal pathology.

[1] Pezzella N, Bove G, Tammaro R, Franco B. OFD1: One gene, several disorders. Am J Med Genet C Semin Med Genet. 2022 Mar;190(1):57-71. doi: 10.1002/ajmg.c.31962. Epub 2022 Feb 2. PMID: 35112477; PMCID: PMC9303915.

[2] Franco B, Bruel AL, Thauvin-Robinet C. Oral-Facial-Digital Syndrome Type I. 2002 Jul 24 [Updated 2023 May 11]. GeneReviews® [Internet]. University of Washington, Seattle. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1188/

Statement of originality: This case was entirely my own work. The conceptualisation of the case, the drafting of the manuscript and the creation of the poster were all performed by myself. Contributions from the additional authors included kindly providing specialist knowledge and interpretation through involvement in the case as well as input around academic writing and final edits. No generative AI was used.