Ischemic stroke in a patient with Fahr’s disease carrying biallelic mutations in theMYORGgene

Abstract

Fahr’s disease (FD) is a neurodegenerative disorder characterized by symmetric calcifications in the bilateral basal ganglia and dentate nuclei. Mutations in six genes are known to cause FD. In the present case, a 44-year-old woman was admitted because of bradykinesia that had started developing 3 years ago. Brain CT and MRI revealed severe calcification in the bilateral basal ganglia, thalamus, dentate nuclei, and subcortical white matter. Whole-exome sequencing revealed two previously described compound heterozygous mutations within the MYORG gene. About one year later, the patient developed sudden-onset left-sided hemiparesis. The MRI revealed a small infarction in the right internal capsule. Therefore, the present case findings expand the clinical spectrum of FD. Importantly, the association between ischemic stroke and FD needs to be further studied.

Case report: 10 years follow-up of psychosis due to Fahr’s disease complicated by a left temporal stroke

“…The concomitance of ischemic stroke with FD has already been described (5,6,20) and linked to genetic mutations related to FD in two cases (21,22). Calcification in the walls of small vessels has been implicated as the potential cause (6).…”

Fahr's disease linked to a novel mutation in MYORG variants manifesting as paroxysmal limb stiffness and dysarthria: Case report and literature review

“…We searched through PubMed until April 1, 2023 for relevant studies and scanned the reference lists in the identified articles. We reviewed all reported cases of PFBC with biallelic MYORG mutations and summarized all the mutation sites in Table 1 (Arkadir et al, 2019 ; Chelban et al, 2020 ; Chen, Lin, et al, 2020 ; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Fei et al, 2021 ; Ferreira & de Oliveira, 2019 ; Forouhideh et al, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Li et al, 2022 ; Liu et al, 2021 ; Malaquias et al, 2020 ; Peng et al, 2018 ; Ramos et al, 2019 ; Sadok et al, 2023 ; Saranza et al, 2020 ; Taglia et al, 2019 ; Tekin et al, 2021 ; Tsai et al, 2022 ; Yang et al, 2022 ; Yao et al, 2018 ; Zeng et al, 2021 ). Data for 62 families have been reported, 51% of the patients were men and 49% were women.…”

“…Similar to previous studies (Grangeon et al, 2019 ; Taglia et al, 2019 ; Zeng et al, 2021 ), we observed that dysarthria is a prominent feature and the most common manifestation in patients with MYORG ‐PFBC, as well as other motor signs, including ataxia, dystonia, dyskinesia, Parkinsonism, and akinetic hypertonic syndrome. Ischemic stroke was also reported in five cases, and none of them had risk factors for stroke (Gao et al, 2022 ; Grangeon et al, 2019 ; Li et al, 2022 ; Yang et al, 2022 ). Central neuropathic pain was also observed in a 43‐year‐old Chinese woman (Peng et al, 2018 ).…”

“…Thirty‐six mutation sites were found only in compound heterozygous mutations, 23 only in homozygous mutations, and five mutation sites, including c.225G>A, c.348_349insCTGGCCTTCCGC, c.1333C>T, c.1831C>T, and c.1967T>C, were found in both homozygous and compound heterozygous mutations. The most frequent mutation sites were c.348_349insCTGGCCTTCCGC, followed by c.1967T>C, c.1333C>T, c.687G>T, and c.782_783GC>TT, which were found in 10 families (Chinese and Frenchman; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Grangeon et al, 2019 ; Li et al, 2022 ; Yang et al, 2022 ; Yao et al, 2018 ), five families (Chinese and Frenchman; Chelban et al, 2020 ; Chen, Cen et al, 2020 ; Grangeon et al, 2019 ; Liu et al, 2021 ), three families (Chinese; Grangeon et al, 2019 ; Peng et al, 2018 ; Yang et al, 2022 ), three families (Chinese and Frenchman; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Li et al, 2022 ), and three families (Chinese; Chen, Cen, et al, 2020 ; Yao et al, 2018 ; Zeng et al, 2021 ), respectively. We opined that these mutation sites may be “hot spots” for Chinese and Frenchmen.…”

“…The novel frameshift mutation identified in our patient was located in the unknown function domain. To date, 24 mutations in this domain have been reported (Chelban et al, 2020 ; Chen, Lin, et al, 2020 ; Chen, Cen, et al, 2020 ; Chen et al, 2019 ; Ferreira & de Oliveira, 2019 ; Gao et al, 2022 ; Grangeon et al, 2019 ; Kume et al, 2020 ; Li et al, 2022 ; Malaquias et al, 2020 ; Sadok et al, 2023 ; Taglia et al, 2019 ; Tekin et al, 2021 ; Yang et al, 2022 ; Yao et al, 2018 ; Zeng et al, 2021 ), suggesting that this region plays an important role in MYORG , leading to PFBC. Therefore, more studies are recommended to investigate the correlations between mutation sites, pathogenicity‐implicated imaging findings, and clinical phenotypes.…”