A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review

Abstract

Primary familial brain calcification (PFBC) is a disorder in which pathologic calcification of the basal ganglia, cerebellum, or other brain regions with bilateral symmetry occurs. Common clinical symptoms include dysarthria, cerebellar symptoms, motor deficits, and cognitive impairment. Genetic factors are an important cause of the disease; however autosomal recessive (AR) inheritance is rare. In 2018, the myogenesis-regulated glycosidase (MYORG) gene was the first to be associated with AR-PFBC. The present case is a 24-year-old woman with AR-PFBC that presented with migraine at the age of 16 years. Symmetrical patchy calcifications were seen in the bilateral cerebellopontine nuclei, thalamus, basal ganglia, and radiocoronal area on computed tomography and magnetic resonance imaging. AR-PFBC with migraine as the main clinical symptom is rare. Whole-exome sequencing revealed a compound heterozygous mutation in the MYORG gene, one of which has not been previously reported. Our case highlights the pathogenic profile of the MYORG gene, and demonstrates the need for exclusion of calcium deposits in the brain for migraine patients with AR inheritance.

The Genetics of Primary Familial Brain Calcification: A Literature Review

“…A wide range of speech disturbances, including dystonic, spastic, scanned, or slurred speech, can be presented in PFBC [ 16 ]; especially, a speech disturbance is the cardinal presentation of patients with MYORG variants [ 3 , 22 ]. The other neurological symptoms include various types of seizures, headaches/migraines, pyramidal signs, and stroke [ 21 , 23 , 24 , 25 , 26 , 27 ].…”

“…The missense change is the most common variant type in the MYORG gene, followed by in-frame indels, nonsense, and frameshift variations. There is no obvious hotspot of pathogenic variants ( Figure 1 e) [ 3 , 10 , 22 , 24 , 25 , 26 , 27 , 30 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ]. Pathogenic variants cause the loss of the glycosidase function of MYORG , which may lead to abnormal protein glycosylation and metabolic disturbance.…”