Faculty, Staff and Student Publications
Publication Date
4-1-2024
Journal
American Journal of Medical Genetics Part A
Abstract
Aicardi-Goutières syndrome (AGS) is an autosomal recessive inflammatory syndrome that manifests as an early-onset encephalopathy with both neurologic and extraneurologic clinical findings. AGS has been associated with pathogenic variants in nine genes: TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1, LSM11, and RNU7-1. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic/likely pathogenic variants in the known genes. One of the genes associated with AGS, SAMHD1, has also been associated with a spectrum of cerebrovascular diseases, including moyamoya disease (MMD). In this report, we describe a 31-year-old male referred to genetics for MMD since childhood who lacked the hallmark features of AGS patients but was found to have compound heterozygous SAMHD1 variants. He later developed mitral valve insufficiency due to recurrent chordal rupture and ultimately underwent a heart transplant at 37 years of age. Thus, these data suggest that SAMHD1 pathogenic variants can cause MMD without typical AGS symptoms and support that SAMHD1 should be assessed in MMD patients even in the absence of AGS features.
Keywords
Male, Humans, Child, Adult, SAM Domain and HD Domain-Containing Protein 1, Moyamoya Disease, Mitral Valve, Mutation, Nervous System Malformations, Autoimmune Diseases of the Nervous System, Brain Diseases, moyamoya disease, SAMHD1, Aicardi-Goutières syndrome, stroke
DOI
10.1002/ajmg.a.63486
PMID
38041217
PMCID
PMC11700514
PubMedCentral® Posted Date
4-1-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes