Objective: We report a detailed description of a family affected by a hereditary multisystem disorder associated with moyamoya syndrome.
Methods: In this family case report, we evaluated 9 members of the same family originating from Algeria. Investigations included neuroimaging, cardiologic and ophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, chromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and enzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci previously linked to moyamoya, on chromosomes 10 (ACTA2) and 17.
Results: Five males related through a maternal lineage were affected, suggesting an X-linked inheritance. Four of them had symptomatic moyamoya syndrome with an onset of acute neurologic manifestations between 4 and 32 years. Hypergonadotropic hypogonadism, azoospermia, short stature of postnatal onset (-2 to -4 SD in adulthood), premature graying of hair, and dysmorphism were present in all patients. The other features of the disease included early cataract in 4, dilated cardiomyopathy in 3, and partial growth hormone deficiency in 2 members. Muscle biopsy data did not reveal signs of a mitochondrial disorder. All conditions known to be associated with moyamoya syndrome such as Down syndrome, neurofibromatosis, and sickle cell disease were excluded. We also excluded linkage to the 2 loci previously reported to be involved in autosomal dominant syndromic and nonsyndromic moyamoya. Carrier females had normal phenotype and clinical history.
Conclusions: These data strongly suggest that this family is affected by a hereditary moyamoya multisystem disorder with X-linked recessive pattern of inheritance.