Novel EXT1 variants cause divergent symptom severity in multiple cartilaginous exostoses: a family report

Multiple cartilaginous exostoses (MCE) are a rare genetic disorder characterized by multiple osteochondromas in the metaphysis of long bones.

Case Presentation.

We report a 15-year-old male patient, his father, and his brother, all presenting varied severity of the same symptom. The patient exhibited symptoms since infancy, with osteochondromas affecting mobility and causing joint deformities. Whole exome sequencing identified a pathogenic NM_000127.3(EXT1):c.1056 + 2 T > G and a likely pathogenic NM_000127.3(EXT1):c.1047G > T variant in the EXT1 gene, both novel.

Despite three decades since the discovery of the EXT1 gene, MCE diagnosis may be delayed until adolescence or adulthood. This report contributes to clinical understanding, emphasizing the importance of early diagnosis, genetic analysis, and potential treatment approaches, to mitigate long-term deformities and complications in MCE patients.