SAMHD1 – Moyamoya Disease

A single 31-year-old male with childhood-onset moyamoya disease was found to harbor compound heterozygous SAMHD1 variants in the absence of classical Aicardi-Goutières syndrome features (PMID:38041217). He presented with encephalopathy, dystonia (HP:0001332), and hepatosplenomegaly (HP:0001433) but lacked microcephaly and sterile pyrexia; he later developed mitral valve insufficiency leading to heart transplantation. The inheritance pattern is autosomal recessive, consistent with other SAMHD1-related phenotypes, but no segregation data are available. Functional data on SAMHD1 support its role in dNTPase regulation and nuclear localization in immune and viral restriction contexts, yet direct assays in vascular models are lacking. At present, this evidence yields a Limited gene–disease association, with only one proband reported and no additional familial or cohort studies. Key take-home: SAMHD1 should be considered in the genetic evaluation of autosomal recessive moyamoya disease, even in the absence of AGS stigmata.

References

• American journal of medical genetics. Part A • 2024 • SAMHD1 compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of Aicardi-Goutières syndrome PMID:38041217

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