PRRT2 mutations: exploring the phenotypical boundaries.
BACKGROUND
Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene have been identified in patients with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large family with ICCA containing one individual with febrile seizures (FS) and one individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of patients with different types of infantile epilepsy.


METHODS
We screened a cohort of 460 patients with B(F)IC or ICCA, fever related seizures or infantile epileptic encephalopathies. All patients were tested for point mutations using direct sequencing.


RESULTS
We identified heterozygous mutations in 16 individuals: 10 familial and 6 sporadic cases. All patients were diagnosed with B(F)IC, ICCA or PD. We were not able to detect mutations in any of the other epilepsy syndromes. Several mutation carriers had learning disabilities and/or impaired fine motor skills later in life.


CONCLUSIONS
PRRT2 mutations do not seem to be involved in the aetiology of FS or infantile epileptic encephalopathies. Therefore B(F)IC, ICCA and PD remain the core phenotypes associated with PRRT2 mutations. The presence of learning disabilities or neuropsychiatric problems in several mutation carriers calls for additional clinical studies addressing this developmental aspect in more detail.
['Djémié|Tania|T|', 'Weckhuysen|Sarah|S|', 'Holmgren|Philip|P|', 'Hardies|Katia|K|', 'Van Dyck|Tine|T|', 'Hendrickx|Rik|R|', 'Schoonjans|An-Sofie|AS|', 'Van Paesschen|Wim|W|', 'Jansen|Anna C|AC|', 'De Meirleir|Linda|L|', 'Selim|Laila Abdel Moteleb|LA|', 'Girgis|Marian Y|MY|', 'Buyse|Gunnar|G|', 'Lagae|Lieven|L|', 'Smets|Katrien|K|', 'Smouts|Iris|I|', 'Claeys|Kristl G|KG|', 'Van den Bergh|Vic|V|', 'Grisar|Thierry|T|', 'Blatt|Ilan|I|', 'Shorer|Zamir|Z|', 'Roelens|Filip|F|', 'Afawi|Zaid|Z|', 'Helbig|Ingo|I|', 'Ceulemans|Berten|B|', 'De Jonghe|Peter|P|', 'Suls|Arvid|A|']
D004827:Epilepsy D005260:Female D006801:Humans D007859:Learning Disabilities D008297:Male D008565:Membrane Proteins D019957:Motor Skills Disorders D009419:Nerve Tissue Proteins D010375:Pedigree D010641:Phenotype D017354:Point Mutation
EPILEPSY CLINICAL NEUROLOGY GENETICS NEUROGENETICS