Paroxysmal central nervous system disorders

Gene: PRRT2

Green List (high evidence)

Comment on mode of inheritance: Heterozygous PRRT2 variants are a well known cause of 'Convulsions, familial infantile, with paroxysmal choreoathetosis' - most commonly the c.649dupC variant. There are also several individuals reported in literature with biallelic PRRT2 variants and a more severe neurologic presentation, including childhood-onset epilepsy, dyskinesia, and episodic ataxia. Hence, the MOI should be changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.

Created: 27 Jul 2026, 2:35 p.m. | Last Modified: 27 Jul 2026, 2:39 p.m.

Panel Version: 4.6

PMID: 38316952 Koko et al., 2024
Sudanese family reported with a homozygous PRRT2 variant [NC_000016.10(NM_145239.3):c.-65-1G > A] and self-limited infantile epilepsy. No intellectual disability seen, siblings preformed well in school. Parents were het carriers. The mild presentation of sibs is hypothesised to come from a hypomorphic character of the splice variant.

PMID: 36247910 Martorell et al., 2022
Report of a female patient, presented with epileptic seizures at 2 months old. She started walking at 18 months, but had a very severe language delay. Episodic ataxia was noted at 2yrs. 2 PRRT2 variants detected in trans: c.649dupC and c.649delC. History of afebrile seizures noted on mother's side (mother het for c.649dupC). Proband diagnosed with severe ID and ASD.

PMID: 31193310 El Achkar et al., 2019
Report of a male patient with a severe phenotype including infantile epilepsy with status epilepticus, paroxysmal dyskinesia and episodic ataxia. He harboured comp het PRRT2 variants c.649dupC, p.Arg217Profs*8 (maternal) and c.916G>A, p.Ala306Thr (paternal). Mother and brother het for c.649dupC were asymptomatic. On father's side, there is family history of episodic confusion and episodic hemiparesis (only father genotyped). Normal development noted at 5 years old, no cognitive impairment seen in the proband.

PMID: 25595153 Delcourt et al., 2015
Report of 5 patients with biallelic PRRT2 variants: 3 homozygous for c.649dupC, P1 was comp het for c.649dupC and a de novo whole PRRT2 gene deletion, and P5 was homozygous for PRRT2 c.913G>A, p.Gly305Arg. While 4 individuals had some learning difficulties and ADHD, their cognition was normal. All 5 patients had seizures with onset before 6 months of life; episodic ataxia was present in patients 1-4 (not normally seen in heterozygous individuals); cerebellar atrophy was seen on MRI in 2 cases.

PMID: 23126439 Labate et al., 2012
Homozygous c.649dupC mutation in PRRT2 detected in 2 sibs from a consanguineous Italian family resulted in ID, episodic ataxia, and absences. 4 other affected family members, het for the same mutation, presented only with benign familial infantile seizures / familial paroxysmal kinesigenic dystonia.

DOI: 10.1055/s-0045-1810051 Eshrif & Adofani, 2025
Case report of a family with epilepsy and dyskinesia due to a homozygous PRRT2 variant c.649dup, p.(Arg217Profs8). 3 sibs affected, all 3 presented with focal seizures at 3-8 months old, and 2/3 individuals also had dyskinesia. Family history not discussed, parents assumed to be unaffected from the pedigree.

https://doi.org/10.1016/j.mgene.2016.12.005 Kishk et al., 2017
Case report of an Egyptian family - two sibs with Infantile convulsions and choreoathetosis and a homozygous PRRT2 variant c.649dupC. No physical or cognitive disabilities noted. Het parents unaffected.

The PRRT2-related neurodevelopmental and movement disorder with or without seizures (biallelic_autosomal) entry has Moderate confidence in G2P. PRRT2 is not yet associated with a recessive disorder in OMIM or ClinGen (accessed 27th July 2026).

Created: 27 Jul 2026, 2:34 p.m. | Last Modified: 27 Jul 2026, 2:34 p.m.

Panel Version: 4.4

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis, OMIM:602066; PRRT2-associated paroxysmal movement disorder, MONDO:0100556

Publications

• 23126439
• 25595153
• 31193310
• 36247910
• 38316952

Green List (high evidence)

I don't know

Review and rating from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) was collated (February 2019) on behalf of London North GLH for the GMS Neurology specialist test group.

Created: 2 Sep 2019, 2:39 p.m. | Last Modified: 2 Sep 2019, 2:39 p.m.

Panel Version: 0.26

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (February 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group.

Created: 2 Sep 2019, 1:39 p.m. | Last Modified: 2 Sep 2019, 1:39 p.m.

Panel Version: 0.23

Green List (high evidence)

Episodic ataxia - limited evidence?

Created: 2 Sep 2019, 1:30 p.m. | Last Modified: 2 Sep 2019, 1:30 p.m.

Panel Version: 0.22

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

Phenotypes
Convulsions, familial infantile, with paroxysmal choreoathetosis, 602066; Episodic kinesigenic dyskinesia 1, 128200; Seizures, benign familial infantile, 2, 605751

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