Inherited white matter disorders

Gene: EIF2AK2

Green List (high evidence)

A further 5 families reported (PMID: 33236446) harbouring 3 different variants in this gene (including the first homozygous case). Clinical presentation was prominent in all cases for dystonia with onset in infancy or childhood, with subsequent generalisation. 3 unrelated individuals additionally developed mild ID, spasticity, and brain MRI alterations (including white matter abnormalities); while 6 individuals from the remaining 2 families had only isolated dystonia.

Created: 28 Sep 2021, 4:07 p.m. | Last Modified: 28 Sep 2021, 4:07 p.m.

Panel Version: 1.138

Association with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation reported in both OMIM and G2P (probable).

PMID: 32197074 (2020) - Distinct de novo missense variants were identified in eight unrelated individuals who all share a notable phenotypic overlap of developmental delay, cognitive impairment, white matter alterations, dysarthria or lack of speech, and neurologic regression with febrile illness. Other variable features included hypotonia (7/8), hypertonia (7/8), ataxia (6/8), dystonia (5/8), tremor (3/8) and seizures (4/8). Functional data confirm reduced kinase activity compared to the wildtype protein product, and authors predict a dominant-negative effect.
Sources: Literature

Created: 3 Aug 2020, 4:41 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, 618877

Publications

• 32197074
• 33236446