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Developmental Delay, Hypomyelination, and Nystagmus: Case and Approach
L G Ramanzini1, J M Frare2, T F Lopes1
1Medical School, Department of Neuropsychiatry, Center of Health Sciences, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
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.
Insights
Pelizaeus-Merzbacher-like disease (PMLD) is a rare genetic disorder causing developmental delay and hypomyelination. Diagnosis involves GJC2 gene variants, distinguishing it from PMD and offering a better prognosis.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy.
- It is caused by homozygous variants in the GJC2 gene.
- PMLD typically presents in infancy with nystagmus, developmental delay, and diffuse brain hypomyelination.
Observation:
- A 3-year-old boy presented with nystagmus and global developmental delay.
- Brain MRI revealed diffuse hypomyelination, including the cerebellum.
- Initial suspicion of Pelizaeus-Merzbacher disease (PMD) was ruled out due to negative PLP1 gene variant testing.
Findings:
- Exome sequencing identified GJC2 gene variants, confirming a diagnosis of PMLD.
- The patient exhibited global developmental delay, hypomyelination, and nystagmus.
- Unlike PMD, PMLD frequently involves brainstem and cerebellar hypomyelination with normal brainstem auditory evoked potentials.
Implications:
- The clinical presentation of nystagmus, developmental delay, and hypomyelination warrants consideration of both PMD and PMLD.
- Distinguishing PMLD from PMD is crucial due to differences in affected brain regions and prognosis.
- PMLD, while rare, should be included in the differential diagnosis for children with these neurological symptoms.
