WARS2 Deficiency: Phenotypic Spectrum

PhenotypeTypical OnsetGenotype
Epilepsy 1, 2Neonatal or infantile onsetBiallelic WARS2 pathogenic variants
Movement disorder 3Childhood or early adulthood onsetHypomorphic WARS2 variant c.37T>G (p.Trp13Gly) in trans w/WARS2 pathogenic variant 4
1.

Including developmental and epileptic encephalopathy (DEE) and other seizure types

2.

WARS2-related epilepsy has also been referred to as NEMMLAS (neurodevelopmental disorder, mitochondrial, w/abnormal movements and lactic acidosis, with or without seizures) (see Nomenclature).

3.

Primarily levodopa-responsive parkinsonism/dystonia and progressive myoclonus-ataxia/hyperkinetic movement disorder

4.

The WARS2 variant c.37T>G (p.Trp13Gly) is a hypomorphic variant that is disease causing only when in trans with a WARS2 loss-of-function variant (see Molecular Genetics, Special technical laboratory considerations).

From: WARS2 Deficiency

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