ABSTRACT
OBJECTIVE: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by recurrent attacks of hyperkinetic movements. PKD can be isolated or associated with benign infantile seizures as part of the infantile convulsions with choreoathetosis (ICCA) syndrome. Mutations in the PRRT2 gene were recently identified in patients with PKD and ICCA. We studied the prevalence of PRRT2 mutations and characteristics of the patients in a European population of patients with PKD and ICCA. METHODS: Patients were recruited through the 1996-2011 database of our DNA bank, to which physicians refer DNA with a putative diagnosis and clinical information. Two movement disorders experts reviewed the information on patients with a putative diagnosis of PKD. Patients who fulfilled the criteria for PKD and ICCA were included. The PRRT2 coding sequence was analyzed by direct sequencing. RESULTS: Among 42 index cases of unrelated families referred with a putative diagnosis of PKD, a total of 34 patients, including 32 with isolated PKD and 2 with ICCA, were selected for genetic analysis. Mutations introducing premature termination codons were identified in 22 of 34 patients including 13 of 14 families and 9 of 20 patients with sporadic cases. The previously described c.649dupC/pArg217ProfsX8 and c.629dupC/pAla211SerfsX14 were present, respectively, in 17 patients and 1 patient; we also report 3 novel mutations: c.649delC/pArg217GlufsX12 in 2 patients, and c.562C>T/pGln188X and c.649C>T/pArg217X, each in 1 patient. The group with mutations was characterized by a younger age at onset (9 years) compared with the patients without mutations (15 years; p < 0.01). CONCLUSION: Mutations in PRRT2 are a major cause of PKD in familial and sporadic cases in the European population.
Subject(s)
Chorea/genetics , Dyskinesias/genetics , Epilepsy, Benign Neonatal/genetics , Membrane Proteins/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Seizures/genetics , Adult , Age of Onset , Chorea/diagnosis , Dyskinesias/diagnosis , Epilepsy, Benign Neonatal/diagnosis , Humans , Pedigree , Seizures/diagnosis , Syndrome , White People/geneticsABSTRACT
The various causes of tremor are considered by order of prevalence in the elderly. 1) Essential tremor occurs in 5% of the population beyond 65 years of age. It is characterized by a tremor accompanying muscle activity, and interesting, when complete, the two upper limbs, the head and the voice, with variable degree of severity. Its progression is very slow. The diagnostic criteria are only clinical, but require ruling out iatrogenic and metabolic causes. 2) Tremor in Parkinson's disease is opposed point by point to essential tremor. However, confusion may occur due to some intermediate clinical situations. In these cases, pharmacology or DaTSCAN data can help to distinguish between the two conditions. 3) Other causes are considered, giving the priority to practical and therapeutic aspects. The psychological consequences of tremor should be taken into account to improve the quality of life of patients with tremor. Terms which stigmatize, such as senile tremor, or terms which minimize the relational and social consequences of tremor, such as benign tremor, should be discarded.
