Grange‐Like Phenotype Associated With an RNF213 Pathogenic Variant: Expanding the Vasculopathy Spectrum
Makaleler > Tam Makale · 2026
Yazarlar: Serife Ozturk Yilmaz, Ayca Yigit, Sevcan Hatipoglu, Semra Gursoy, Aytac Gulcu, Tuncer Turhan, Mert Pekerbas, Alper Soylu, Ugur Ozbek, Ozlem Giray Bozkaya
American Journal of Medical Genetics Part A, Uluslararası, Wos, 2026, cilt 200, ss 1923-1928
DOI: 10.1002/ajmg.a.70158
Özet
Grange syndrome, caused by biallelic loss-of-function variants in YY1AP1, is characterized by multivascular stenoses, renovascular hypertension, brachydactyly, syndactyly, and mild cognitive impairment. Although RNF213 variants are typically associated with Moyamoya disease and systemic arterial stenosis, evidence suggests that pathogenic RNF213 variants may contribute to a broader vascular phenotype. We describe a 15-year-old girl with Moyamoya vasculopathy presenting with bilateral renal artery stenosis, brachydactyly, and intellectual disability. Her history included left-arm weakness and seizures at 10 months of age. She underwent surgical revascularization at 1.5 and 3 years of age for Moyamoya disease. Upon evaluation for hypertension, the patient was diagnosed with bilateral renal artery stenosis. Physical examination revealed dysmorphic features including deep-set eyes, up slanting palpebral fissures, a broad nasal bridge, low-set, posteriorly rotated ears, a broad left thumb, brachydactyly, and syndactyly of the toes. Whole-exome sequencing was negative; trio whole-genome sequencing identified a de novo, likely pathogenic RNF213 variant (c.12341C > G). This case expands the phenotypic spectrum associated with RNF213 variants, presenting a Grange-like phenotype. Our study highlights RNF213 as a candidate gene for such phenotypes. A negative YY1AP1 result does not exclude a Grange-like phenotype, emphasizing the need for comprehensive genetic testing and early vascular surveillance.