Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders in which there is a permanent deficit in the amount of myelin in the central nervous system, either due to its abnormal formation or due to alterations in the differentiation or migration of oligodendrocytes. In general terms, this group of diseases is clinically characterized by developmental delay, hypotonia, ataxia, spasticity, and variable intellectual disability. Radiologically, hypomyelination is characterized by diffuse hyperintensity on T2/FLAIR images and often appears to affect the white matter uniformly. On the other hand, unlike demyelinating disorders in which the T1 sequence signal is hypointense, changes in this sequence can be isointense, slightly hypointense, or hypertensive. This pattern can be missed if several consecutive sequences are not examined, so it must be observed in at least 2 imaging tests performed at an interval of at least 6 months in a patient over 1 year of age.
Among the most common disorders is Pelizaeus-Merzbacher disease (PMD), caused by pathogenic variants in the PLP1 gene, as well as a series of diseases with similar clinical and radiological characteristics that are called PMD-like (PMDL), caused by defects in GJC2, AIMP1 or HSPD. Among the other hypomyelinating diseases, the disorders associated with Pol-III, Cockayne syndrome, trichothiodystrophy with photosensitivity or Tay syndrome, hypomyelination with atrophy of the basal ganglia and cerebellum or hypomyelination with congenital cataract, stand out.
