A new clinical-MRI leukodystrophy entity has been identified under the terms CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter).
Clinical signs and genetics
It is classically associated with:
an onset between the age of 2 and 5 years of cerebello-spastic syndrome, often revealed or exacerbated by a mild head trauma or a banal viral infection, leading to death on average after 5 to 10 years of evolution
diffuse involvement of the supratentorial white matter on MRI, cavitary in appearance
an autosomal recessive mode of inheritance
a neuropathological aspect of cavitary orthochromatic leukodystrophy with an increase in the number of oligodendrocytes sometimes taking a foamy appearance.
A total of 148 cases have been reported to date.
The involvement in the etiology of this syndrome of the five genes each encoding one of the subunits of the eIF2B translation initiation complex, whose role is to regulate protein synthesis in the event of cell stress, has made it possible to then extend the clinical phenotype.
Within these pathologies linked to abnormalities of the eIF2B gene have thus been described forms of early infantile onset (Cree leukoencephalopathy), even neonatal, associated with extra-neurological signs, rapidly fatal, and more and more frequently juvenile or adults (ovarioleukodystrophy), beginning with cognitive or behavioral disorders of slower evolution.