A Novel NDUFV2 Variant in an Asymptomatic Adolescent Girl with Progressive Cavitating Leukoencephalopathy

Introduction: Pathogenic variants in several genes encoding components of the mitochondrial respiratory chain have been linked to various clinical phenotypes such as progressive cavitating leukoencephalopathy (PCL). The association between PCL, previously linked to numerous gene mutations in the literature, and the NDUFV2 gene mutations has emerged as a recent and noteworthy discovery. PCL is generally diagnosed in symptomatic patients during the early years of life, mostly in infancy.

Case presentation: In a previously healthy 12-year-old Turkish girl, a computed tomography scan taken for minor head trauma incidentally revealed suspicious hypodense areas in the periventricular white matter. Subsequently, a magnetic resonance imaging evaluation was performed. There was no history of motor regression, irritability, or seizures up to the age of 12. The case exhibited normal neurological and cranial nerve examinations. Magnetic resonance imaging detected bilateral periventricular T2/FLAIR hyperintensities with cystic areas suggestive of PCL. Whole-exome sequencing revealed the presence of a homozygous p.R222C missense variant in the NDUFV2 gene. Over a 6-year follow-up period, the patient remained asymptomatic, and there were no discernible changes in the magnetic resonance imaging findings.

Conclusion: This case underscores the association between a potentially causal variant at the NDUFV2 locus and PCL. It is worth noting that this novel variation in PCL can not only manifest with symptoms in the infantile period but also remain asymptomatic into adolescence.