The clinical spectrum of Grange syndrome: A case report of a novel variant and literature review

Grange syndrome (OMIM: 602531) is an ultra-rare disorder characterized by multiple steno-occlusive disease of the renal, abdominal, coronary, and cerebral arteries. Our report describes the first family with confirmed Grange syndrome from Saudi Arabia and expands the spectrum of its clinical and radiological phenotype. We present three siblings with Grange syndrome caused by a novel biallelic frameshift variant of YY1AP1 , who demonstrate a variable phenotype. We report two asymptomatic cases, with a prospective observation, and recommend initiating clinical surveillance for asymptomatic individuals. Finally, we highlight the importance of genetic testing as part of stroke workup in children and young adults. • Grange syndrome is an ultra-rare multisystem disorder that exhibits a broad clinical spectrum with both interfamilial and intrafamilial variability • Diagnosis of Grange syndrome requires a high index of suspicion. A milder phenotype is likely underdiagnosed & under-reported in the existing literature • Diagnostic confirmation is critical to ensure appropriate clinical management and facilitate timely surveillance