Developmental Delay, Hypomyelination, and Nystagmus: Case and Approach

ABSTRACT

Pelizaeus-Merzbacher-like disease (PMLD, OMIM #608804) is an autosomal recessive hypomyelinating leukodystrophy caused by homozygous variants in the GJC2 gene. It usually presents in the first months of life with nystagmus, developmental delay, and diffuse hypomyelination on brain magnetic resonance imaging (MRI). We report a case of a 3-year-old boy that presented with nystagmus and global developmental delay. MRI showed diffuse hypomyelination, including the cerebellum. Pelizaeus-Merzbacher disease (PMD) was suspected; however, no pathological variants of the PLP1 gene were found. Exome sequencing found variants in the GJC2 gene, leading to a diagnosis of PMLD. The combination of global developmental delay, hypomyelination, and nystagmus in a child should raise suspicion of PMD and PMLD. Unlike PMD, however, hypomyelination of the brainstem and cerebellum are frequently seen and brainstem auditory evoked potentials are usually normal in PMLD. The latter has an overall better prognosis than the former as well. Epidemiological studies on leukodystrophies have found conflicting results on which disease is more common. However, PMLD is a rare leukodystrophy and both PMLD and PMD should be considered in any child with developmental delay, hypomyelination, and nystagmus.

KEYWORDS:

• Hypomyelination
• nystagmus
• Pelizaeus-Merzbacher-like disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

All authors contributed significantly to the creation of this manuscript; each fulfilled the criteria as established by the ICMJE.

Ethical approval statement

Informed consent has been obtained from the patient’s family.

Additional information

Funding

There is no funding associated with the work featured in this article.