Report of a young patient with brain calcifications with a novel homozygous MYORG variant

Primary familial brain calcifications (PFBC) is characterized by bilateral and symmetrical deposition of inorganic phosphate, mainly in the basal ganglia, thalamus, cerebellum, and dentate nucleus. The symptoms resemble other neuropsychiatric conditions, such as Parkinsonism, dementia, migraine, and mood disorders. Pathogenic variants in six genes have been associated with this disorder, four linked to the autosomal dominant mode (SLC20A2, PDGFRB, PDGFB, and XPR1) and two linked to the recessive fashion (MYORG and JAM2). Herein, we report a young 24-year-old patient with a medical history of bilateral and symmetrical brain calcification and neuropsychiatric symptoms that include movement disturbances (chorea and dystonia), chronic migraine, unexplained tinnitus, and mood swings. After whole-exome sequencing, she was diagnosed with a novel homozygous MYORG variant (c.912_914del; p.(Ser305del)). In silico analysis showed that the variant is located on the extracellular domain of MYORG protein and is predicted to be disease-causing (likely pathogenic), implying that protein features might be affected. This study describes the second Brazilian case of MYORG PFBC-causative gene. Furthermore, it highlights the early age and onset of symptoms of the proband, especially in regard to movement disorders.

Automated summary

This study reports a young patient with bilateral and symmetrical brain calcification and neuropsychiatric symptoms. Whole-exome sequencing revealed a novel homozygous MYORG variant, which is predicted to be disease-causing. This finding expands our knowledge of the genetic basis of primary familial brain calcifications.