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Intellectual disability
Gene: PRRT2

PRRT2 (proline rich transmembrane protein 2)
EnsemblGeneIds (GRCh38): ENSG00000167371
EnsemblGeneIds (GRCh37): ENSG00000167371
OMIM: 614386, Gene2Phenotype
PRRT2 is in 13 panels

8 reviews

Ida Ertmanska (Genomics England Curator)

I don't know

Comment on list classification: While there are a few individuals reported in literature with biallelic PRRT2 variants and severe intellectual disability (e.g., PMID: 36247910), most patients have normal cognition. More consistent features include early onset epilepsy, episodic ataxia, and dyskinesia. Hence, this gene should remain Amber on Intellectual disability.
Created: 27 Jul 2026, 2:26 p.m. | Last Modified: 27 Jul 2026, 2:26 p.m.

Panel Version: 10.69

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, 11:53 a.m. | Last Modified: 27 Jul 2026, 2:21 p.m.

Panel Version: 10.69

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

Created: 27 Jul 2026, 11:53 a.m.
Last Modified: 27 Jul 2026, 2:21 p.m.
Panel version: 10.69

Arina Puzriakova (Genomics England Curator)

New publication identified by Dmitrijs Rots (PMID: 36180924) highlights an individual with a 'severe neurodevelopmental disorder' and a c.649dup (p.R217fs*8) variant in the PRRT2 gene in trans with the recurrent 16p11.2 BP4-BP5 deletion. 16p11.2 haploinsufficiency itself is known to be associated with ID (ISCA-37400-Loss) and therefore it is difficult to ascertain the contribution of the PRRT2 variant to the patients phenotype. This should be considered if further cases arise, but leaving this gene as Amber for now.
Created: 27 Feb 2023, 2:38 p.m. | Last Modified: 27 Feb 2023, 2:38 p.m.

Panel Version: 4.79

Created: 27 Feb 2023, 2:38 p.m.
Last Modified: 27 Feb 2023, 2:38 p.m.
Panel version: 4.79

Dmitrijs Rots (Children's Clinical University Hospital)

I don't know

New case with ID and biallelic variant reported in 36180924.
Created: 8 Oct 2022, 11:04 p.m. | Last Modified: 8 Oct 2022, 11:04 p.m.

Panel Version: 3.1737

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

36180924

Created: 8 Oct 2022, 11:04 p.m.
Last Modified: 8 Oct 2022, 11:04 p.m.
Panel version: 3.1737

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Changed from Green to Amber, as there is not enough evidence in the literature to rate this gene as Green. Rated as Amber as biallelic variants do cause ID but there is not enough evidence to promote further.
Created: 7 Aug 2018, 3:36 p.m.

added watch list tag
Created: 7 Aug 2018, 3:30 p.m.

Internal clinical team notes that it is the biallelic variants of PRRT2 that leads to more significant phenotypes that includes ID. In the literature there are a number of cases for monoallelic variants, the majority of people have seizures ( this gene is green on our Genetic Epilepsy Syndromes panel), and the minority of which have some intellectual component but seems to be mild, so is not in the scope of the ID panel. It is also not clear on whether the ID is secondary to the seizure phenotype in some cases. For biallelic variants, there are only 2 cases currently reported with more a more significant ID phenotype.
Created: 7 Aug 2018, 3:29 p.m.

Comment on phenotypes: changed phenotypes as we are only interested in those associated to biallelic variants of this gene due to association to ID
Created: 27 Jul 2018, 12:04 p.m.

Comment on mode of inheritance: changed to Biallelic as we are only interested in biallelic variants of this gene due to association to ID
Created: 27 Jul 2018, 12:02 p.m.

From Red review from external reviwer this gene was reaccessed. I think there is some general confusion as we have annotated this gene to the wrong phenotype BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME (AD) and not AUTOSOMAL RECESSIVE MENTAL RETARDATION (AR), so is probably why Zornitza Stark rated this gene as Red. I have now added the publications PMID:23352743, 23398397, 21937992 to support ID and suggested MOI is changed and the phenotypes are amended. Past onto internal clinical team for further review and consideration to confirm keeping gene rated as Green or Amber
Created: 26 Jul 2018, 1:30 p.m.

biallelic phenotype includes ID
Created: 26 Jul 2018, 1:16 p.m.

phenotypes associated to biallelic phenotype with includes ID
Created: 26 Jul 2018, 1:16 p.m.

Comment on publications: added publications to support the ID phenotype
Created: 26 Jul 2018, 1:14 p.m.

From Liu YT et al. (2016) PMID: 27172900 Mutations in the proline-rich transmembrane protein 2 gene (PRRT2, NM_145239.2) have been identified to be the causes of many neurological diseases. Heterozygous PRRT2 mutations cause paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), infantile convulsions and choreoathetosis (ICCA), hemiplegic migraine (HM), episodic ataxia (EA), paroxysmal torticollis, or a combination of them ( Although rarely identified, patients with biallelic or homozygous PRRT2 mutations presented complex forms of PKD in combination with intellectual disability or cerebellar atrophy (PMID: 23352743, 25595153, 23398397).
Created: 26 Jul 2018, 1:12 p.m.

G2P lists AUTOSOMAL RECESSIVE MENTAL RETARDATION phenotype, confirmed biallelic loss of function, the evidence listed is a deep sequencing publication Najmabadi et al (20111) PMID:21937992
Created: 26 Jul 2018, 12:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy; mental retardation; movement disorders; paroxysmal disorder, AUTOSOMAL RECESSIVE MENTAL RETARDATION

Created: 26 Jul 2018, 12:41 p.m.

Panel version: 2.297

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Not convinced intellectual disability is part of the phenotype
Created: 20 Jun 2018, 3:19 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 20 Jun 2018, 3:19 p.m.

Panel version: 2.104

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME

Publications

21937992

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_omim_20150205_epilepsies;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:09 p.m.

Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; omim_20150205_epilepsies; manju_list; UKGTN_v12; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:12 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

25529582
omim.org
Personal communication with NIHRBRRD BRIDGE SPEED
Version 12 ukgtn.nhs.uk

Created: 2 Aug 2017, 9:53 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:42 a.m.

Panel version: 0.306

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber

Phenotypes

Epilepsy
mental retardation
movement disorders
paroxysmal disorder
Autosomal recessive mental retardation

Tags

watchlist

OMIM

614386

Clinvar variants

Variants in PRRT2

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

27 Feb 2023, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439

7 Aug 2018, Gel status: 2