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Novel phenotype in a family with infantile convulsions and paroxysmal choreoathetosis syndrome and PRRT2 gene mutation
Brain & Development xxx (2013) xxx–xxx www.elsevier.com/locate/braindev
Letter to the Editor Novel phenotype in a family with infantile convulsions and paroxysmal choreoathetosis syndrome and PRRT2 gene mutation
in this family extends the clinical phenotype of this syndrome.
Dear Editor,
Acknowledgment
We read with great interest the article by Torisu et al. who reported “Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes” [1]. PRRT2 has been reported as causative gene of benign infantile convulsions with paroxysmal dyskinesia [2]. We report a family with a PRRT2 gene mutation and a novel clinical phenotype. This 10-year-old male patient is the first child of non-consanguineous parents, with normal psychomotor development. At 6 months of age, he had a cluster of focal seizures, lasting 30–40 s, successfully treated with phenobarbital. At age of 9 years, he presented episodes with pallor, sweating, and proximal, irregular, not-stereotyped and arrhythmic involuntary movements resembling ballism, followed by choreiform movements and dystonic postures of the trunk. Attacks lasted a few seconds and occurred daily. These movements were typically precipitated by sudden movement, emotional stress, or cold. He described an aura of fear and discomfort. Treatment with lorazepam and, later on, with carbamazepine was effective. At 3 years of age, the patient had repetitive stereotypies such as body rocking and head rolling and palpebral and facial tics, which disappeared after few months. Sporadic attacks of migraine without aura have been present since the age of 7 years. His mother suffered from benign infantile convulsions and sporadic facial motor tics, repetitive stereotypies starting in childhood and sporadic attacks of paroxysmal choreoathetosis dyskinesia identical to her son’s, which spontaneously disappeared. Molecular analysis of the patient and his mother of the PRRT2 gene showed the alreadydescribed heterozygous frameshift mutation in the exon 2 (c.649dupC, p.Arg217Profs8) [3]. In this family, the episodes of paroxysmal dyskinesia are characterized by brief and violent movements of limbs resembling ballism, unusual in PRRT2 mutation patients, as well as the presence of tics is rarely reported [4]. Furthermore, the child and his mother presented repetitive, brief, and voluntary stereotypes such as body rocking and head rolling, never reported so far. In summary, the presence of ballism, transient motor tics and stereotypies
We would like to thank Mrs. Giuliana Soncini for her technical assistance. We thank the Cell line and DNA bank of pediatric movement disorders of the Telethon Genetic Biobank Network (GTB07001) and of the Eurobiobank.
References [1] Torisu H, Watanabe K, Shimojima K, Sugawara M, Sanefuji M, Ishizaki Y, et al. Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes. Brain Dev 2013. http://dx.doi.org/ 10.1016/j.braindev.2013.05.009. [2] Wang JL, Cao L, Li XH, Hu ZM, Li JD, Zhang JG, et al. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain 2011;134:3493–501. [3] Li J, Zhu X, Wang X, Sun W, Feng B, Du T, et al. Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis. J Med Genet 2012;49:76–8. [4] Friedman J, Olvera J, Silhavy JL, Gabriel SB, Gleeson JG. Mild paroxysmal kinesigenic dyskinesia caused by PRRT2 missense mutation with reduced penetrance. Neurology 2012;79:46–8.
⇑
Carlo Fusco Angelo Russo Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy E-mail address: [email protected] Federica Invernizzi Molecular Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy Daniele Frattini Pediatric Neurology Unit, Arcispedale Santa Maria Nuova,
⇑ Corresponding author. Address: Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Viale Risorgimento 80 – 42100, Reggio Emilia, Italy. Tel.: +39 0522295968; fax: +39 0522295046.
0387-7604/$ - see front matter Ó 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.braindev.2013.09.001
2
V.V. Fusco et al. / Brain & Development xxx (2013) xxx–xxx
Reggio Emilia, Italy Francesco Pisani Child Neuropsychiatric Unit, University of Parma, Italy Barbara Garavaglia Molecular Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
Letter to the Editor Novel phenotype in a family with infantile convulsions and paroxysmal choreoathetosis syndrome and PRRT2 gene mutation
in this family extends the clinical phenotype of this syndrome.
Dear Editor,
Acknowledgment
We read with great interest the article by Torisu et al. who reported “Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes” [1]. PRRT2 has been reported as causative gene of benign infantile convulsions with paroxysmal dyskinesia [2]. We report a family with a PRRT2 gene mutation and a novel clinical phenotype. This 10-year-old male patient is the first child of non-consanguineous parents, with normal psychomotor development. At 6 months of age, he had a cluster of focal seizures, lasting 30–40 s, successfully treated with phenobarbital. At age of 9 years, he presented episodes with pallor, sweating, and proximal, irregular, not-stereotyped and arrhythmic involuntary movements resembling ballism, followed by choreiform movements and dystonic postures of the trunk. Attacks lasted a few seconds and occurred daily. These movements were typically precipitated by sudden movement, emotional stress, or cold. He described an aura of fear and discomfort. Treatment with lorazepam and, later on, with carbamazepine was effective. At 3 years of age, the patient had repetitive stereotypies such as body rocking and head rolling and palpebral and facial tics, which disappeared after few months. Sporadic attacks of migraine without aura have been present since the age of 7 years. His mother suffered from benign infantile convulsions and sporadic facial motor tics, repetitive stereotypies starting in childhood and sporadic attacks of paroxysmal choreoathetosis dyskinesia identical to her son’s, which spontaneously disappeared. Molecular analysis of the patient and his mother of the PRRT2 gene showed the alreadydescribed heterozygous frameshift mutation in the exon 2 (c.649dupC, p.Arg217Profs8) [3]. In this family, the episodes of paroxysmal dyskinesia are characterized by brief and violent movements of limbs resembling ballism, unusual in PRRT2 mutation patients, as well as the presence of tics is rarely reported [4]. Furthermore, the child and his mother presented repetitive, brief, and voluntary stereotypes such as body rocking and head rolling, never reported so far. In summary, the presence of ballism, transient motor tics and stereotypies
We would like to thank Mrs. Giuliana Soncini for her technical assistance. We thank the Cell line and DNA bank of pediatric movement disorders of the Telethon Genetic Biobank Network (GTB07001) and of the Eurobiobank.
References [1] Torisu H, Watanabe K, Shimojima K, Sugawara M, Sanefuji M, Ishizaki Y, et al. Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes. Brain Dev 2013. http://dx.doi.org/ 10.1016/j.braindev.2013.05.009. [2] Wang JL, Cao L, Li XH, Hu ZM, Li JD, Zhang JG, et al. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain 2011;134:3493–501. [3] Li J, Zhu X, Wang X, Sun W, Feng B, Du T, et al. Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis. J Med Genet 2012;49:76–8. [4] Friedman J, Olvera J, Silhavy JL, Gabriel SB, Gleeson JG. Mild paroxysmal kinesigenic dyskinesia caused by PRRT2 missense mutation with reduced penetrance. Neurology 2012;79:46–8.
⇑
Carlo Fusco Angelo Russo Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy E-mail address: [email protected] Federica Invernizzi Molecular Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy Daniele Frattini Pediatric Neurology Unit, Arcispedale Santa Maria Nuova,
⇑ Corresponding author. Address: Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Viale Risorgimento 80 – 42100, Reggio Emilia, Italy. Tel.: +39 0522295968; fax: +39 0522295046.
0387-7604/$ - see front matter Ó 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.braindev.2013.09.001
2
V.V. Fusco et al. / Brain & Development xxx (2013) xxx–xxx
Reggio Emilia, Italy Francesco Pisani Child Neuropsychiatric Unit, University of Parma, Italy Barbara Garavaglia Molecular Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy