Novel MYORG mutation in a patient with primary familial brain calcification: A case report

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by idiopathic calcifications in the basal ganglia, thalamus, and cerebellum. It presents with varied neurological symptoms, including tremors, ataxia, and cognitive decline. Here, we report a 44-year-old male, born of second-degree consanguinity, who developed clumsiness, gait disturbances, and speech difficulties over six years, with progressive cognitive impairment. Brain imaging revealed bilateral calcifications in the basal ganglia, dentate nuclei, thalami, and deep white matter. Whole-exome sequencing identified a novel homozygous nonsense mutation (c.1381A>T, p.Lys461*) in the MYORG gene, confirmed by Sanger sequencing, with predicted pathogenicity based on ACMG guidelines. Nerve conduction studies showed demyelinating motor neuropathy, a rare finding in PFBC, expanding the known clinical spectrum of MYORG -related cases. Management focused on symptomatic relief, including beta-blockers for tremor control and physical therapy. Genetic counseling was provided, though segregation analysis was limited by financial constraints. This case highlights the role of genetic testing in diagnosing PFBC and underscores the importance of multidisciplinary care. Further research is needed to explore the molecular mechanisms of MYORG mutations and develop targeted therapies for PFBC.