Three unrelated individuals with strikingly similar phenotypes were found to have a shared genotype of heterozygous de novo stop-loss variants in CLDN11. This has been described as autosomal dominant hypomyelinating leukodystrophy 22 (HLD22) (OMIM # 619328).
All three individuals presented with global developmental delay in early infancy particularly with respect to motor skills. Intellectual abilities were more mildly impaired.
All patients experienced expressive speech delays with oromotor hypotonia and articulation problems. They all had pyramidal signs with spasticity. These included limb hyperreflexia, extensor plantar responses, arching of the neck, and muscle hypertonia.
There are some shared features between these individuals which may help to differentiate from Pelizaeus-Merzbacher disease and other hypomyelinating leukodystrophies. Firstly, it is noted that all three have hypermetropia. Secondly, the MRI patterns showed evidence of moderate rather than severe myelin deficit, as well as some progress in myelination in the central and peripheral white matter regions.
CLDN11