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Review
. 2023 Dec;11(12):e2276.
doi: 10.1002/mgg3.2276. Epub 2023 Sep 7.

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

Tianxue Zhao  1 , Shaokun Xu  2 , Siyue Liu  1 , Juan Xu  1 , Xianfeng Zhang  1 , Yuhong Zhan  1
Affiliations
Review

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

Tianxue Zhao et al. Mol Genet Genomic Med. 2023 Dec.

Abstract

Background: Primary familial brain calcification (PFBC) is a rare hereditary neurodegenerative disorder associated with the MYORG gene; however, the clinical and radiological characteristics of MYORG-PFBC remain unclear.

Methods: We present relevant medical data obtained from a patient affected by PFBC with a novel MYORG variant and conducted a mutational analysis of MYORG in her family members. We reviewed all reported PFBC cases with biallelic MYORG mutations until April 1, 2023, and summarized the associated clinical and radiological features and mutation sites.

Results: The patient (22-year-old woman) exhibited paroxysmal limb stiffness and dysarthria for 3 years. Computed tomography revealed calcifications in the paraventricular white matter, basal ganglia, thalamus, and cerebellum. Whole-exome sequencing revealed a novel homozygous frameshift variant (c.743delG: p.G248Afs*32) in exon 2 of the MYORG gene (NM_020702.5). To date, 62 families and 64 mutation sites have been reported. Among the reported biallelic MYORG mutations, 57% were homozygous and 43% were compound heterozygous. Individuals with biallelic MYORG mutations experience more severe brain calcification with approximately 100% clinical penetrance. Ten single heterozygous mutation sites are associated with significant brain calcifications.

Conclusion: All patients with primary brain calcification, particularly younger patients without a family history of the disease, should be screened for MYORG mutations.

Keywords: Fahr's disease; MYORG gene; brain calcification; case report; homozygous mutation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pedigree and genetic analysis results of the patient and her family. (a) The family pedigree (Genome reference sequence: GRCh37/hg19). The index patient (II‐1) is marked by a black arrow. A filled circle represents a family member with a homozygous MYORG mutation, and a half‐filled square or circle represents a family member who is a carrier of a MYORG mutation. The c.743delG heterozygous mutation in the MYORG gene in the patient's mother (b), father (c) and younger brother (e). (d) The c.743delG homozygous mutation in the MYORG gene in the patient.
FIGURE 2
FIGURE 2
Computed tomography (CT) and magnetic resonance imaging (MRI) findings of the patient. CT scan showing symmetric calcifications in the cerebellum (a), basal ganglia (b), thalamus (b), and paraventricular (c) (red arrows). MRI showed symmetric calcifications in the dentate nucleus of the cerebellum (d), basal ganglia (e), dorsolateral nucleus of the thalamus (e), and paraventricular (f) (red arrows). CT, computed tomography; MRI, magnetic resonance imaging.
See this image and copyright information in PMC

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