Primary familial brain calcification in a patient with a novel compound heterozygous mutation in MYORG presenting with an acute ischemic stroke: a case report

Abstract

Primary familial brain calcification (PFBC) is known as Fahr's disease (FD) or familial idiopathic basal ganglia calcification (FIBGC). PFBC is a genetically heterogeneous disease characterized by extensive intracranial calcium deposition. Currently, pathogenic variants in six genes (SLC20A2, PDGFB, PDGFRB, XPR1, MYORG and JAM2) have been associated with PFBC. MYORG was the first autosomal-recessive causal gene discovered in PFBC patients. PFBC is also a clinically heterogeneous disorder. Patients mostly present with movement disorders, cognitive impairment and psychiatric symptoms, and acute cerebrovascular attacks are rare. Here, we report the case of a PFBC patient with a novel compound heterozygous mutation in MYORG presenting with an acute ischemic stroke. A 52-year-old man had recurrent and progressively exacerbated transient-ischemic-attack-like episodes and finally had an acute ischemic stroke. Brain computed tomography (CT) showed extensive and symmetric calcifications. Brain magnetic resonance imaging (MRI) revealed an acute ischemic infarction. A novel compound heterozygous mutation in MYORG (p.R116_S117insLAFR and p.Q445*) was found in this patient by whole-exome sequencing (WES). Therefore, this patient was diagnosed with PFBC-MYORG and an acute ischemic stroke. He was treated with antiplatelet drugs (aspirin and clopidogrel) and received rehabilitation training. There was no physical disability at discharge. More efforts should be made to explore the association between acute ischemic strokes and PFBC.

Keywords: Fahr’s disease (FD); MYORG; acute ischemic stroke; case report; primary familial brain calcification (PFBC).

Figure 1

Timeline of major clinical events in the patient. CT, computed tomography; MRI, magnetic resonance imaging.

Figure 2

Imaging examination. (A-D) CT scans show calcifications in the cerebellum, periventricular white matter, basal ganglia, thalamus and brainstem; (E) CT scans show the cerebellum with subtle antero-superior hemispheric lobe atrophy; (F) MRI DWI shows acute ischemic infarction of the right thalamus; (G,H) MRA and CTA exclude intracranial and extracranial vessel stenosis, occlusion, aneurysm and vascular malformation. CT, computed tomography; MRI, magnetic resonance imaging; DWI, diffusion weighted image; MRA, magnetic resonance angiography; CTA, computed tomography angiography.

Figure 3

Sequence analysis indicates a nonsense mutation (c.1333C>T) and nonframeshift indel variant (c.348_349insCTGGCCTTCCGC). Control, reference sequence; case, sequence of the patient.