Primary brain calcification due to homozygous MYORG mutation: a case report of seizures, psychosis, and cerebellar involvement in a young adult

Abstract Background Primary brain calcification (PBC), is a rare genetic disorder involving idiopathic calcifications in the basal ganglia and other brain regions, often inherited autosomally. It must be distinguished from Fahr's syndrome, which is secondary to metabolic causes like parathyroid abnormalities. Diagnostic challenges arise when transient endocrine issues mimic secondary etiologies. Case description A 27-year-old female presented with a 12-year history of absence seizures, evolving to generalized tonic-clonic episodes, psychosis (commanding hallucinations, Capgras delusion), aggression, and cerebellar signs (dystonia, ataxia, tremors). Family history included a similarly affected brother. Imaging (NCCT and MRI) revealed bilateral calcifications in basal ganglia, thalamus, dentate nucleus, and cerebellum, with atrophy and infarct. Initial labs showed hypocalcemia and elevated PTH (100.8 pg/mL), suggesting secondary hyperparathyroidism, but normalization occurred post-vitamin D/calcium supplementation. Whole exome sequencing identified a homozygous pathogenic MYORG variant (c.488G>A, p.Trp163Ter), confirming PBC type 7. Management focused on antiepileptics, antipsychotics (e.g., olanzapine, lumateperone), and supplementation, with partial symptom control. Discussion This case illustrates PBC's heterogeneity, presenting with early seizures, psychosis, and cerebellar involvement despite autosomal recessive inheritance. The transient hyperparathyroidism, likely vitamin D-related, initially misled diagnosis, highlighting the role of genetic testing in resolving ambiguities. Symptomatic treatment prevails, with genetic counselling recommended.