Genotype-phenotype Correlation in Pelizaeus Merzbacher Disease and Pelizaeus Merzbacher-like Disease

Abstract

Among the hypomyelinating diseases of childhood, Pelizaeus Merzbacher disease (PMD) is caused by X-linked proteolipid protein (PLP) gene mutations, whereas patients without mutations of PLP gene-called Pelizaues Merzbacher-like disease (PMLD) have recessive gap junction protein α12 (gap junction alpha-12/gap junction gamma-2) gene mutations. The aim of this study was to evaluate clinical severity and progression in time in patients with PMD and PMLD. Methods: The motor developmental stages of the patients were reviewed; disease severity was classified according to the walking ability they were able to achieve. Progression pattern was determined according to comparison of neurological findings at the time of the study and at follow-up visits. Patients with PMD and PMLD were compared in terms of disease severity and progression rates as well as patient groups with a unique causative mutation were analyzed individually. Results: There were 9 patients with PMD (mean age 15.2±3.1) and 11 patients with PMLD (mean age 12.4±1.9). The presence of severe disease was more common in patients with PMD when compared to PMLD. In X-linked PMD, missense mutations were associated with the most severe disease and rapid progression, while deletion mutations were associated with mild disease severity and slow progression. Disease severity and progression patterns seemed to be heterogenous in different causative mutations of PMLD. Conclusion: Although PMLD might have milder disease phenotype when compared to PMD, certain causative mutations in different genetic traits may cause different disease severity and progression patterns.