Ataxia - paediatric

Gene: KCNA2

Green List (high evidence)

Missense variants cluster within the ion transporter domain (Decipher)
The proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 is a mutational hotspot (Doring, 2021)

LOF mechanism is commonly used in papers, but are often referring to DN
Missense variants demonstrate all of LOF, GOF and DN mechanisms.

Variability btw carriers of the same variant is reported, and intrafamilial variability is reported (Döring (2021))

Created: 21 May 2021, 4:21 a.m. | Last Modified: 21 May 2021, 4:21 a.m.

Panel Version: 0.7652

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Developmental and epileptic encephalopathy 32, MIM#616366

Publications

• PMID: 33802230
• 29050392

Mode of pathogenicity
Other

Green List (high evidence)

Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations.

Created: 12 Sep 2020, 4:24 a.m. | Last Modified: 12 Sep 2020, 4:24 a.m.

Panel Version: 0.240

Ataxia is part of the phenotype.
Sources: Expert list

Created: 27 Dec 2019, 5:17 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Early infantile encephalopathy 32, MIM#616366

Publications

• 29050392