Prepair 1000+

Gene: WARS2

Green List (high evidence)

Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances.

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. NEMMLAS is associated with childhood or early adulthood onset.

p.(Trp13Gly) is a hypomorphic allele associated with NEMMLAS and only causes disease when in trans with a more deleterious variant. It does not cause disease in a homozygous state (PMID: 37107582).

It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition (GeneReviews PMID: 37824696).

Created: 21 Jan 2025, 2:47 a.m. | Last Modified: 21 Jan 2025, 2:47 a.m.

Panel Version: 1.1257

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures MIM#617710; Parkinsonism-dystonia 3, childhood-onset MIM#619738

Publications

• 37107582
• 37824696