A novel SAMD9 SAMD9 mutation causing MIRAGE syndrome: An expansion and review of phenotype, dysmorphology, and natural history

摘要

Germline gain‐of‐function variants in SAMD9 have been associated with a high risk of mortality and a newly recognized constellation of symptoms described by the acronym MIRAGE: Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy. Here, we describe two additional patients currently living with the syndrome, including one patient with a novel de novo variant for which we provide functional data supporting its pathogenicity. We discuss features of dysmorphology, contrasting with previously described patients as well as drawing attention to additional clinical features, dysautonomia and hearing loss that have not previously been reported. We detail both patients’ courses following diagnosis, with attention to treatment plans and recommended specialist care. Our patients are the oldest known with arginine‐substituting amino acid variants, and we conclude that early diagnosis and multidisciplinary management may positively impact outcomes for this vulnerable group of patients.