Hypomyelinating leukodystrophy and movement disorders

Abstract

Abstract Hypomyelinating leukodystrophies (HLDs) are a heterogeneous group of disorders caused by primary deficit in myelin development; they are radiologically characterized by mild T2 hyperintensity with near normal T1 signal of the cerebral white matter. While most HLDs occur during infancy or childhood, adult-onset phenotypes are reported as well. To date, HLDs have not been extensively discussed in the literature on movement disorders apart from segregated case reports. From the perspective of movement disorders, HLDs commonly manifest as spastic ataxia, except for disorders such as hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) and fucosidosis, where dystonia predominates. In addition, dystonia can be associated with the 18q deletion syndrome and KIF1C- and NKX6-2-related spastic ataxia. Chorea can be observed in the striatal variant of POLR3A, 18q deletion syndrome, and KIF1C-related disorders. Associated morphological features such as facial dysmorphism, hypodontia, early cataract, and skeletal and limb dysmorphism often provide vital clues to recognize these HLDs. Additional imaging clues include striatal atrophy in the H-ABC syndrome, spinal cord T2 hyperintensities in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, intracranial calcification in Cockayne syndrome, and pallidal T2 hypointensity in fucosidosis. Early recognition of these clinicoradiological clues will be helpful in ordering a comprehensive genetic panel to confirm the diagnosis and determine the prognosis and therapeutic outcome.