RESUMO
Prrt2 is a neuron-specific protein expressed at axonal and pre-synaptic domains, involved in synaptic neurotransmitter release and modulation of intrinsic excitability. Mutations in PRRT2 cause a spectrum of autosomal dominant paroxysmal neurological disorders including epilepsy, movement disorders, and hemiplegic migraine and show incomplete penetrance and variable expressivity. We assessed the diagnostic rate of PRRT2 in a cohort of Italian patients with epilepsy and/or paroxysmal kinesigenic dyskinesia (PKD) and evaluated genotype-phenotype correlations. Clinical data were collected using a structured questionnaire. Twenty-seven out of 55 (49.1%) probands carried PRRT2 heterozygous pathogenic variants, including six previously known genotypes and one novel missense mutation. A family history of epilepsy starting in the first year of life and/or PKD was strongly suggestive of a PRRT2 pathogenic variant. Epilepsy patients harbouring PRRT2 pathogenic variants showed earlier seizure onset and more frequent clusters compared with PRRT2-negative individuals with epilepsy. Moreover, we did also identify individuals with PRRT2 pathogenic variants with atypical age at onset, i.e. childhood-onset epilepsy and infantile-onset PKD. However, the lack of a clear correlation between specific PRRT2 genotypes and clinical manifestations and the high incidence of asymptomatic carriers suggest the involvement of additional factors in modulating expressivity of PRRT2-related disorders. Finally, our study supports the pleiotropic and multifaceted physiological role of PRRT2 gene which is emerging from experimental neuroscience.
Assuntos
Distonia/genética , Epilepsia/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Lactente , Itália , Masculino , Mutação , Convulsões/genética , Adulto JovemRESUMO
Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.