MYRF – Mild Encephalopathy with Reversible Myelin Vacuolization

Mild encephalopathy with reversible myelin vacuolization is characterized by transient splenial lesions and reversible cerebral white matter vacuolization in the context of mild neurologic symptoms. While sporadic and infectious etiologies are frequently implicated, familial and recurrent presentations suggest an underlying genetic basis.

In 2018, exome sequencing of a three-generation pedigree revealed a heterozygous c.1208A>G (p.Gln403Arg) variant in MYRF co-segregating with recurrent encephalopathy and extensive but reversible myelin vacuolization in six affected individuals across two unrelated families([PMID:29265453]).

Autosomal dominant inheritance is supported by segregation of the MYRF c.1208A>G variant in four additional affected relatives beyond the index cases, with absence in unaffected members of both pedigrees([PMID:29265453]).

Functional luciferase assays demonstrated that the c.1208A>G (p.Gln403Arg) variant significantly diminishes transcriptional activity of the MYRF N-terminal DNA-binding domain, consistent with a loss-of-function mechanism underlying disrupted oligodendrocyte differentiation([PMID:29265453]).

No conflicting evidence has been reported in this disease context, though MYRF exhibits pleiotropy in diaphragmatic hernia, ocular development, and sex differentiation syndromes, underscoring the need for phenotype-specific evaluation.

Collectively, the data fulfill moderate clinical validity criteria for MYRF in mild encephalopathy with reversible myelin vacuolization. Genetic testing for MYRF variants should be considered in recurrent or familial cases to guide diagnosis, management, and genetic counseling.

References

• Annals of neurology • 2018 • MYRF is associated with encephalopathy with reversible myelin vacuolization. PMID:29265453

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