Grange syndrome: An identifiable cause of stroke in young adults

Abstract

Grange syndrome is a disorder characterized by arterial occlusive disease, hypertension, congenital cardiac defects, bone fragility, brachysyndactyly, and learning disabilities. It was first described in four members of the same family and in two sporadic cases thereafter, suggesting the possibility of various patterns of inheritance. We report on the case of an 18-year-old female presenting with subarachnoid hemorrhage due to the rupture of a basilar artery aneurysm, and with distinctive systemic features including extensive vasculopathy, facial dysmorphisms and brachysyndactyly, consistent with the diagnosis of Grange syndrome. Although rare and not fully characterized, Grange syndrome should be included in the differential diagnosis of stroke at young age.

Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease

“…Additional cases of Grange syndrome have been described with similar vascular complications. [8][9][10] The steno-occlusive arterial lesions and involvement of the cerebral and renal arteries led to the classification of the vascular disease in Grange syndrome as FMD, and both unifocal and multifocal lesions have been described in affected individuals. Interestingly, the intracranial location of the cerebrovascular occlusions and the formation of compensatory collateral vessels at the base of brain in individuals with Grange syndrome are similar to those observed in Moyamoya disease.…”

The Retroperitoneal Space

“…Finally, Grange syndrome is an autosomal recessive disorder that is characterized by arterial occlusive processes, HBP, congenital cardiac defects, brachysyndactyly (invariably present), bone fragility, and learning disabilities 15 . Patient 5 had had surgery to correct bilateral syndactyly and several bone fractures, which fitted this clinical hypothesis.…”

“…Moreover, he developed HBP secondary to renal artery stenosis manifesting with epistaxis, severe headaches, and LVH, which further consolidated the diagnosis. The association between arterial stenosis and syndactyly can only be found in Grange syndrome; 15 therefore, this serves as a hallmark for this condition.…”

Identification of the first homozygous intragenic deletion in the YY1AP1 gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome

“…They reported a first family with four out of nine siblings affected by the same vascular symptoms. Since 1998, only 10 families and 15 cases have been reported (Ciuffetelli Alamo et al, 2019; Grange et al, 1998; Guo et al, 2017; Karakaya et al, 2023; Raggio et al, 2021; Rath et al, 2019; Saida et al, 2019; Volonghi et al, 2012; Wallerstein et al, 2006; Weymann et al, 2001). This syndrome is characterized by the stenosis or the occlusion of multiple arteries (renal, cerebral, and abdominal), hypertension, syndactyly, increased bone fragility, and developmental delay.…”