CLDN11-related hypomyelinating leukodystrophy (HLD22)
General description
CLDN11-related hypomyelinating leukodystrophy, also known as hypomyeliating leukodystrophy (HLD22), is a newly identified genetic disorder caused by de novo stop-loss variants in the CLDN11 gene. This gene encodes claudin-11, a tight junction protein essential for myelination in the central nervous system.
Clinically, individuals with CLDN11 related hypomyelinating leukodystrophy exhibit developmental delays, particularly in motor and speech functions. Neurological symptoms include spasticity, hypotonia, nystagmus, and contractures. Additionally, hypermetropia is a distinctive ocular feature that sets this condition apart from other hypomyelinating leukodystrophies and may aid in diagnosis. Many affected individuals require mobility aids such as walkers and experience functional challenges like drooling.
References
- Gjervan, Sophia C., et al. "Claudin-11 in health and disease: implications for myelin disorders, hearing, and fertility." Frontiers in Cellular Neuroscience 17 (2024): 1344090.
- Riedhammer, Korbinian M., et al. "De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy." Brain 144.2 (2021): 411-419.
Delayed myelination
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CerebrumCerebral white matter
T1WI show a near-normal signal intensity in the white matter. In contrast, T2WI reveal significant hypomyelination in the cerebral white matter. The progression of the condition is characterized by delayed myelination, with partial catch-up occurring in later childhood.