Disease-causing variants (“mutations”) in CLDN11 have been associated with autosomal dominant Hypomyelinating leukodystrophy-22 (HLD22). To date only 3 patients, all with heterozygous stop-loss variants predicted to extend the mature protein, have been described in the literature. The clinical spectrum of this condition will likely expand as more patients are identified.
Disease-causing variants reported to date have been de novo, meaning the genetic alteration was not inherited, but occurred for the first time in the patient.
Patients have presented with global developmental delay in early infancy particularly with respect to motor skills. Intellectual abilities are more mildly impaired. Expressive speech delays have been accentuated by articulation problems. Other neurological challenges include spasticity, increased reflexes and increased muscle tone.
Compared to other hypomyelinating leukodystrophies, individuals with HLD22 appear more likely to have far-sightedness. There are also unique features to the myelination patterns on MRI.