Developmental trajectory of individuals with Pelizaeus-Merzbacher Disease (PMD).

INTRODUCTION

Pelizaeus-Merzbacher Disease (PMD) is a PLP1-related disorder for which genotype alone is insufficient to reliably determine PMD disease progression. We aim to characterize the developmental outcomes of PMD-affected individuals and evaluate their association with early presentation features.

METHODS

Molecularly confirmed PMD subjects were included. Data on baseline characteristics, developmental, and disease outcomes were abstracted from medical records and, when feasible, supplemented by caregiver interviews. Data were summarized using descriptive statistics.

RESULTS

The study included 111 subjects with milestone acquisition ranging from 9.9% to 68.5% across gross motor, 41.1% to 85.6% across fine motor, and 30.0% to 66.7% across expressive communication skills. Genotype and milestone were not significantly associated. Presentation with stridor (N = 20) was associated with profound impairments (overall non-attainment ranging from 10.0% to 100%). In the absence of stridor, head control by 12 months was associated with developmental outcomes: severe outcomes (overall non-attainment ranging from 0% to 96.0%) when head control was not acquired by 12 months (N = 50), and moderate outcomes (overall non-attainment ranging from 0% to 78.0%) when head control was attained (N = 41). Median time to PMD-related complications was noted to be earlier in the profoundly impaired subtype, compared to the severe and moderate subtypes.

CONCLUSIONS

PMD impairs skill acquisition, with gross motor milestones impacted more than expressive communication. Stridor and lack of head control by 12 months were associated with poor developmental outcomes and disease progression. These insights will support better characterization of disease course for newly diagnosed families, as well as future trial development.