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PRRT2 is mutated in familial and non-familial benign infantile seizures
Nicola Specchio1, Alessandra Terracciano, Marina Trivisano
1Neurology Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, P.zza S. Onofrio 4, 00165 Rome, Italy. nicola.specchio@opbg.net
Background:
Mutations of protein-rich transmembrane protein 2 (PRRT2) were recently associated to benign familial infantile seizures (BFIS) (MIM 605751) and paroxysmal kinesigenic dyskinesias (PKD) (MIM12800).
Aims:
To report mutations of PRRT2 in BFIS, infantile convulsions and choreoathetosis (ICCA), and in sporadic cases affected by benign infantile epilepsy (BIE).
Methods:
A mutational screening of PRRT2 was performed in 5 families, and in 7 sporadic cases affected by BIE. All clinical and neurophysiological details were reviewed.
Results:
Thirty-three members among 5 families were collected. Fifteen individuals had infantile seizures and one had infantile seizures followed by paroxysmal kinesigenic dyskinesia (PKD). We found the c.649_650InsC PRRT2 mutation in all tested patients (13 out of 15). Age at onset ranged from 3.5 to 10 months. Focal seizures, with or without secondary generalization, occurred mainly in cluster. One patient at the age of 11 years presented with PKD successfully treated with carbamazepine. All patients had a normal cognitive development. Two out of 7 non-familial cases (28.5%) carried a de novo PRRT2 mutation: the c.649_650InsC mutation in one with clustered seizures at the age of 5 months and an unreported c.718C-T p.R240X mutation in the other who, after cluster focal seizures at the age of 5 months, experienced absences at the age of 5 years.
Conclusion:
Our findings emphasize that PRRT2 mutations might be responsible of both BFIS and ICCA, but might be causative also for sporadic cases of benign infantile seizures. The phenotypic spectrum comprises BFIS, ICCA, and PKD.
Insights
Mutations in the PRRT2 gene are linked to benign familial infantile seizures (BFIS) and paroxysmal kinesigenic dyskinesias (PKD). This study identifies PRRT2 mutations in both familial and sporadic infantile seizure cases, expanding the known phenotypic spectrum.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Mutations in the protein-rich transmembrane protein 2 (PRRT2) gene have been associated with benign familial infantile seizures (BFIS) and paroxysmal kinesigenic dyskinesias (PKD).
- Understanding the genetic basis of these neurological disorders is crucial for diagnosis and potential therapeutic strategies.
Purpose of the Study:
- To investigate the role of PRRT2 mutations in patients with BFIS, infantile convulsions and choreoathetosis (ICCA), and sporadic benign infantile epilepsy (BIE).
- To delineate the phenotypic spectrum associated with PRRT2 mutations.
Main Methods:
- Conducted mutational screening of the PRRT2 gene in 5 families and 7 sporadic cases of BIE.
- Reviewed clinical and neurophysiological data of affected individuals.
Main Results:
- Identified the c.649_650InsC PRRT2 mutation in 13 out of 15 patients with infantile seizures, with onset between 3.5 and 10 months.
- One patient presented with paroxysmal kinesigenic dyskinesia (PKD) at age 11, successfully treated with carbamazepine.
- Two sporadic cases (28.5%) carried de novo PRRT2 mutations, including c.649_650InsC and a novel c.718C-T p.R240X mutation, presenting with varied seizure types.
Conclusions:
- PRRT2 mutations are a significant cause of both familial and sporadic benign infantile seizures, including ICCA.
- The phenotypic spectrum of PRRT2 mutations encompasses BFIS, ICCA, and PKD.
- All identified patients exhibited normal cognitive development, suggesting a primary role in seizure disorders.
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