Paroxysmal Dyskinesia

Gene: KCNJ10

Green List (high evidence)

Recent description, quickly replicated by other studies - this will be an important gene to consider for paroxysmal kinesigenic dyskinesia even in individuals without features of SESAME syndrome. Other main DDx are PRRT2 and TMEM151A.

Recent paper PMID:38436103 describes mono-allelic and bi-allelic missense variants

Created: 6 Dec 2024, 7:27 p.m. | Last Modified: 6 Dec 2024, 7:27 p.m.

Panel Version: 0.133

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
paroxysmal kinesigenic dyskinesia

Publications

• 38436103
• 38436103

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

11 individuals from 8 unrelated families reported with variants in this gene and paroxysmal dyskinesia. Notably one was the parent of a child with recessive SeSAME syndrome (established gene-disease association). Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.
Sources: Literature

Created: 1 Aug 2024, 5:37 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related

Publications

• 38979912