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Successful control with carbamazepine of family with paroxysmal kinesigenic dyskinesia of PRRT2 mutation.

Chou IC, Lin SS, Lin WD, Wang CH, Chang YT, Tsai FJ, Tsai CH - Biomedicine (Taipei) (2014)

Bottom Line: This study avers PRRT2's high sensitivity for PKD phenotype.Identification of genes underlying pathogenesis will enhance diagnosis and treatment.Function of PRRT2 and its role in PKD warrant further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Children's Hospital, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.

ABSTRACT

Paroxysmal kinesigenic dyskinesia (PKD), a rare paroxysmal movement disorder often misdiagnosed as epilepsy, is characterized by recurrent, brief dyskinesia attacks triggered by sudden voluntary movement. Pathophysiological mechanism of PKD remains not well understood. Ion channelopathy has been suggested, since the disease responds well to ion channel blockers. Mutations in proline-rich transmembrane protein 2 (PRRT2) were recently identified in patients with familial PKD. To extend these genetic reports, we studied a family with clinical manifestations of familial PKD responding well to low dose carbamazepine. Therapeutic dose ranged from 1.5 to 2.0 mg/ kg/day, below that in seizure control. One insertion mutation c.649_650insC (p.P217fsX7) was identified in three patients of the family. This study avers PRRT2's high sensitivity for PKD phenotype. Identification of genes underlying pathogenesis will enhance diagnosis and treatment. Function of PRRT2 and its role in PKD warrant further investigation.

No MeSH data available.


Related in: MedlinePlus

(A) Pedigree of PKC/PKD Taiwanese family: persons designated by sex, disease status (filled symbols represent patients, open symbols normal persons). Index case indicated by arrow. (B) Sequencing results of mutation in PRRT2 gene of index case. Arrow indicates one-base C inserted at nucleotide 650 (c.650insC), causing protein translation shift and stopping after seventh residue.
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Fig1: (A) Pedigree of PKC/PKD Taiwanese family: persons designated by sex, disease status (filled symbols represent patients, open symbols normal persons). Index case indicated by arrow. (B) Sequencing results of mutation in PRRT2 gene of index case. Arrow indicates one-base C inserted at nucleotide 650 (c.650insC), causing protein translation shift and stopping after seventh residue.

Mentions: A twelve-year-old male had two-year history of paroxysmal movement disorder induced by sudden movement or brief exercise; birth, delivery, and development were unremarkable, without significant medical history. Attacks were first evident at age 10, after sudden arm movements; these entailed dystonic flexion and greater internal rotation of left arm and left leg, as well as finger posturing. He was fully aware of his surroundings during the attacks (4-5 times/day), lasting 10-20 (rarely 30) seconds. General physical and neurologic examinations proved normal. Magnetic resonance imaging of the brain, interictal electroencephalogram, and laboratory workup yielded unremarkable results; carbamazepine was prescribed upon diagnosis of paroxysmal kinesigenic dyskinesia. At 200 mg daily (10 mg/kg/day), the patient attained complete resolution of signs that has persisted for the past seven years, no side effects from medication. His father and brother, both diagnosed as PKD, had the same symptoms (Fig. A) ; Table 1 summarizes clinical manifestations. Both were prescribed CBZ as monotherapy (dosage 200 mg/day) to attain total resolution for the past seven years.


Successful control with carbamazepine of family with paroxysmal kinesigenic dyskinesia of PRRT2 mutation.

Chou IC, Lin SS, Lin WD, Wang CH, Chang YT, Tsai FJ, Tsai CH - Biomedicine (Taipei) (2014)

(A) Pedigree of PKC/PKD Taiwanese family: persons designated by sex, disease status (filled symbols represent patients, open symbols normal persons). Index case indicated by arrow. (B) Sequencing results of mutation in PRRT2 gene of index case. Arrow indicates one-base C inserted at nucleotide 650 (c.650insC), causing protein translation shift and stopping after seventh residue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4265013&req=5

Fig1: (A) Pedigree of PKC/PKD Taiwanese family: persons designated by sex, disease status (filled symbols represent patients, open symbols normal persons). Index case indicated by arrow. (B) Sequencing results of mutation in PRRT2 gene of index case. Arrow indicates one-base C inserted at nucleotide 650 (c.650insC), causing protein translation shift and stopping after seventh residue.
Mentions: A twelve-year-old male had two-year history of paroxysmal movement disorder induced by sudden movement or brief exercise; birth, delivery, and development were unremarkable, without significant medical history. Attacks were first evident at age 10, after sudden arm movements; these entailed dystonic flexion and greater internal rotation of left arm and left leg, as well as finger posturing. He was fully aware of his surroundings during the attacks (4-5 times/day), lasting 10-20 (rarely 30) seconds. General physical and neurologic examinations proved normal. Magnetic resonance imaging of the brain, interictal electroencephalogram, and laboratory workup yielded unremarkable results; carbamazepine was prescribed upon diagnosis of paroxysmal kinesigenic dyskinesia. At 200 mg daily (10 mg/kg/day), the patient attained complete resolution of signs that has persisted for the past seven years, no side effects from medication. His father and brother, both diagnosed as PKD, had the same symptoms (Fig. A) ; Table 1 summarizes clinical manifestations. Both were prescribed CBZ as monotherapy (dosage 200 mg/day) to attain total resolution for the past seven years.

Bottom Line: This study avers PRRT2's high sensitivity for PKD phenotype.Identification of genes underlying pathogenesis will enhance diagnosis and treatment.Function of PRRT2 and its role in PKD warrant further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Children's Hospital, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.

ABSTRACT

Paroxysmal kinesigenic dyskinesia (PKD), a rare paroxysmal movement disorder often misdiagnosed as epilepsy, is characterized by recurrent, brief dyskinesia attacks triggered by sudden voluntary movement. Pathophysiological mechanism of PKD remains not well understood. Ion channelopathy has been suggested, since the disease responds well to ion channel blockers. Mutations in proline-rich transmembrane protein 2 (PRRT2) were recently identified in patients with familial PKD. To extend these genetic reports, we studied a family with clinical manifestations of familial PKD responding well to low dose carbamazepine. Therapeutic dose ranged from 1.5 to 2.0 mg/ kg/day, below that in seizure control. One insertion mutation c.649_650insC (p.P217fsX7) was identified in three patients of the family. This study avers PRRT2's high sensitivity for PKD phenotype. Identification of genes underlying pathogenesis will enhance diagnosis and treatment. Function of PRRT2 and its role in PKD warrant further investigation.

No MeSH data available.


Related in: MedlinePlus