PRRT2 Related Epilepsies: A Gene Review

Abstract

PRRT2 encodes for proline-rich transmembrane protein 2 involved in synaptic vesicle fusion and presynaptic neurotransmitter release. Mutations in human PRRT2 have been related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with choreoathetosis, benign familial infantile epilepsies, and hemiplegic migraine. PRRT2 mutations cause neuronal hyperexcitability, which could be related to basal ganglia or cortical circuits dysfunction, leading to paroxysmal disorders. PRRT2 is expressed in the cerebral cortex, basal ganglia, and cerebellum. Approximately, 90% of pathogenic variants are inherited and 10% are de novo. Paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and ballismus. In the benign familial infantile epilepsy (BFIE), seizures are usually focal with or without generalization, usually begin between 3 and 12 months of age and remit by 2 years of age. In 30% of cases of PRRT2-associated PKD, there is an association with BFIE, and this entity is referred to as PKD with infantile convulsions (PKD/IC). PRRT2 mutations are the cause of benign family childhood epilepsy and PKD/IC. On the other hand, PRRT2 mutations do not seem to correlate with other types of epilepsy. The increasing incidence of hemiplegic migraine in families with PRRT2-associated PKD or PKD/IC suggests a common disease pathway, and it is possible to assert that BFIE, paroxysmal kinesigenic dyskinesia, and PKD with IC belong to a continuous disease spectrum of PRRT2-associated diseases.

Keywords

PRRT2 - movement disorders - benign familial infantile epilepsy - paroxysmal dyskinesia

^* These authors equally contributed to the present article.

Publication History

Received: 23 September 2020

Accepted: 21 February 2021

Article published online:
21 May 2021

• References

• 1 Tan G-H, Liu Y-Y, Wang L. et al. PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res 2018; 28 (01) 90-110
• 2 Coleman J, Jouannot O, Ramakrishnan SK. et al. PRRT2 regulates synaptic fusion by directly modulating SNARE complex assembly. Cell Rep 2018; 22 (03) 820-831
• 3 Caltabiano R, Magro G, Polizzi A. et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
• 4 Ranieri C, Di Tommaso S, Loconte DC. et al. In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). Neurogenetics 2018; 19 (02) 77-91
• 5 Fruscione F, Valente P, Sterlini B. et al. PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity. Brain 2018; 141 (04) 1000-1016
• 6 Rossi P, Sterlini B, Castroflorio E. et al. A novel topology of proline-rich transmembrane protein 2 (PRRT2): hints for an intracellular function at the synapse. J Biol Chem 2016; 291 (12) 6111-6123
• 7 Pavone P, Praticò AD, Pavone V. et al. Ataxia in children: early recognition and clinical evaluation. Ital J Pediatr 2017; 43 (01) 6
• 8 Tsai MH, Nian FS, Hsu MH. et al. PRRT2 missense mutations cluster near C-terminus and frequently lead to protein mislocalization. Epilepsia 2019; 60 (05) 807-817
• 9 Chen W-J, Lin Y, Xiong Z-Q. et al. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat Genet 2011; 43 (12) 1252-1255
• 10 Heron SE, Grinton BE, Kivity S. et al. PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. Am J Hum Genet 2012; 90 (01) 152-160
• 11 Ebrahimi-Fakhari D, Saffari A, Westenberger A, Klein C. The evolving spectrum of PRRT2-associated paroxysmal diseases. Brain 2015; 138 (Pt 12): 3476-3495
• 12 Johnson MB, Kawasawa YI, Mason CE. et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 2009; 62 (04) 494-509
• 13 Kang HJ, Kawasawa YI, Cheng F. et al. Spatio-temporal transcriptome of the human brain. Nature 2011; 478 (7370): 483-489
• 14 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
• 15 Li M, Niu F, Zhu X. et al. PRRT2 mutant leads to dysfunction of glutamate signaling. Int J Mol Sci 2015; 16 (05) 9134-9151
• 16 Stelzl U, Worm U, Lalowski M. et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 2005; 122 (06) 957-968
• 17 Schwenk J, Harmel N, Brechet A. et al. High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron 2012; 74 (04) 621-633
• 18 Pavone P, Falsaperla R, Ruggieri M. et al. Clinical course of N-Methyl-D-aspartate receptor encephalitis and the effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15: 84-49
• 19 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
• 20 Lu H-C, Mills AA, Tian D. Altered synaptic transmission and maturation of hippocampal CA1 neurons in a mouse model of human chr16p11.2 microdeletion. J Neurophysiol 2018; 119 (03) 1005-1018
• 21 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A [phone]
• 22 van Vliet R, Breedveld G, de Rijk-van Andel J. et al. PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions. Neurology 2012; 79 (08) 777-784
• 23 Ebrahimi-Fakhari D, Moufawad El Achkar C, Klein C. PRRT2-Associated Paroxysmal Movement Disorders. University of Washington; Seattle: 1993
• 24 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
• 25 Pavone V, Signorelli SS, Praticò AD. et al. Total hemi-overgrowth in pigmentary mosaicism of the (hypomelanosis of) ito type: eight case reports. Medicine (Baltimore) 2016; 95 (10) e2705
• 26 Pavone P, Praticò AD, Gentile G. et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
• 27 Wang J-L, Cao L, Li X-H. et al. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain 2011; 134 (Pt 12): 3493-3501
• 28 Dale RC, Grattan-Smith P, Nicholson M, Peters GB. Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study. Dev Med Child Neurol 2012; 54 (07) 618-623
• 29 Balciuniene J, DeChene ET, Akgumus G. et al. Use of a dynamic genetic testing approach for childhood-onset epilepsy. JAMA Netw Open 2019; 02: e192129
• 30 Termsarasab P, Yang AC, Reiner J, Mei H, Scott SA, Frucht SJ. Paroxysmal kinesigenic dyskinesia caused by 16p11.2 microdeletion. Tremor Other Hyperkinet Mov (NY) 2014; 4: 274
• 31 Labate A, Tarantino P, Viri M. et al. Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences. Epilepsia 2012; 53 (12) e196-e199
• 32 Delcourt M, Riant F, Mancini J. et al. Severe phenotypic spectrum of biallelic mutations in PRRT2 gene. J Neurol Neurosurg Psychiatry 2015; 86 (07) 782-785
• 33 van Roest A, Van de Vel A, Lederer D, Ceulemans B. The clinical and genetic spectrum in infants with (an) unprovoked cluster(s) of focal seizures. Eur J Paediatr Neurol 2020; 24: 148-153
• 34 Liu Q, Qi Z, Wan X-H. et al. Mutations in PRRT2 result in paroxysmal dyskinesias with marked variability in clinical expression. J Med Genet 2012; 49 (02) 79-82
• 35 Becker F, Schubert J, Striano P. et al. PRRT2-related disorders: further PKD and ICCA cases and review of the literature. J Neurol 2013; 260 (05) 1234-1244
• 36 Wang K, Zhao X, Du Y, He F, Peng G, Luo B. Phenotypic overlap among paroxysmal dyskinesia subtypes: Lesson from a family with PRRT2 gene mutation. Brain Dev 2013; 35 (07) 664-666
• 37 Pavone P, Rizzo R, Conti I. et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 2012; 25 (04) 1083-1091
• 38 Gardiner AR, Bhatia KP, Stamelou M. et al. PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. Neurology 2012; 79 (21) 2115-2121
• 39 Okumura A, Shimojima K, Kurahashi H. et al. PRRT2 mutations in Japanese patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia. Seizure 2019; 71: 1-5
• 40 McGuire S, Chanchani S, Khurana DS. Paroxysmal dyskinesias. Semin Pediatr Neurol 2018; 25: 75-81
• 41 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet A 2018; 176 (03) 515-550
• 42 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
• 43 Ruggieri M, Praticò AD, Serra A. et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
• 44 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
• 45 Hatta D, Shirotani K, Hori Y, Kurotaki N, Iwata N. Activity-dependent cleavage of dyskinesia-related proline-rich transmembrane protein 2 (PRRT2) by calpain in mouse primary cortical neurons. FASEB J 2020; 34 (01) 180-191
• 46 Erro R, Bhatia KP. Unravelling of the paroxysmal dyskinesias. J Neurol Neurosurg Psychiatry 2019; 90 (02) 227-234
• 47 Kure S. An atypical case of Thomsen's disease. J Tokyo Med Assoc 1892; 6: 505-514
• 48 Mount LA, Reback S. Familial paroxysmal choreoathetosis. Arch Neurol Psychiatry 1940; 44: 841
• 49 Kertesz A. Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied. Neurology 1967; 17 (07) 680-690
• 50 Richards RN, Barnett HJ. Paroxysmal dystonic choreoathetosis. A family study and review of the literature. Neurology 1968; 18 (05) 461-469
• 51 Lance JW. Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Ann Neurol 1977; 2 (04) 285-293
• 52 Demirkiran M, Jankovic J. Paroxysmal dyskinesias: clinical features and classification. Ann Neurol 1995; 38 (04) 571-579
• 53 Watanabe K, Yamamoto N, Negoro T. et al. Benign complex partial epilepsies in infancy. Pediatr Neurol 1987; 3 (04) 208-211
• 54 Szepetowski P, Rochette J, Berquin P, Piussan C, Lathrop GM, Monaco AP. Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16. Am J Hum Genet 1997; 61 (04) 889-898
• 55 Tomita Ha, Nagamitsu S, Wakui K. et al. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1. Am J Hum Genet 1999; 65 (06) 1688-1697
• 56 Swoboda KJ, Soong B, McKenna C. et al. Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies. Neurology 2000; 55 (02) 224-230
• 57 Caraballo R, Pavek S, Lemainque A. et al. Linkage of benign familial infantile convulsions to chromosome 16p12-q12 suggests allelism to the infantile convulsions and choreoathetosis syndrome. Am J Hum Genet 2001; 68 (03) 788-794
• 58 Zhao S, Li L, Chen Y. et al. Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2 -related disorders. CNS Neurosci Ther 2019
• 59 Valente P, Romei A, Fadda M. et al. Constitutive inactivation of the PRRT2 gene alters short-term synaptic plasticity and promotes network hyperexcitability in hippocampal neurons. Cereb Cortex 2019; 29 (05) 2010-2033
• 60 Liu Y-T, Chen Y-C, Kwan S-Y. et al. Aberrant sensory gating of the primary somatosensory cortex contributes to the motor circuit dysfunction in paroxysmal kinesigenic dyskinesia. Front Neurol 2018; 9: 831
• 61 Symonds JD, McTague A. Epilepsy and developmental disorders: next generation sequencing in the clinic. Eur J Paediatr Neurol 2020; 24: 15-23
• 62 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
• 63 Falsaperla R, Praticò AD, Ruggieri M. et al. Congenital muscular dystrophy: from muscle to brain. Ital J Pediatr 2016; 42 (01) 78
• 64 Lee H-Y, Huang Y, Bruneau N. et al. Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions. Cell Rep 2012; 1 (01) 2-12
• 65 Ji Z, Su Q, Hu L. et al. Novel loss-of-function PRRT2 mutation causes paroxysmal kinesigenic dyskinesia in a Han Chinese family. BMC Neurol 2014; 14: 146
• 66 Vlaskamp DRM, Callenbach PMC, Rump P. et al. PRRT2-related phenotypes in patients with a 16p11.2 deletion. Eur J Med Genet 2019; 62 (04) 265-269
• 67 Zhao G, Liu X, Zhang Q, Wang K. PRRT2 mutations in a cohort of Chinese families with paroxysmal kinesigenic dyskinesia and genotype-phenotype correlation reanalysis in literatures. Int J Neurosci 2018; 128 (08) 751-760
• 68 Balint B, Wiethoff S, Martino D. et al. Quick flicks: association of paroxysmal kinesigenic dyskinesia and tics. Mov Disord Clin Pract (Hoboken) 2018; 5 (03) 317-320
• 69 Li H-F, Yang L, Yin D. et al. Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia. Parkinsonism Relat Disord 2019; 62: 134-140
• 70 Salafia S, Praticò AD, Pizzo E, Greco F, Di Bella D. Hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance findings in a 3-year-old boy. Neurol Neurochir Pol 2013; 47 (06) 584-589
• 71 Legris N, Chassin O, Nasser G, Riant F, Tournier-Lasserve E, Denier C. Acute-onset ataxia and transient cerebellar diffusion restriction associated with a PRRT2 mutation. J Stroke Cerebrovasc Dis 2019; 28 (02) e3-e4
• 72 Lu JG, Bishop J, Cheyette S. et al. A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. Cold Spring Harb Mol Case Stud 2018; 4 (01) a002287
• 73 Tsai M-H, Chan C-K, Chang Y-C. et al. Molecular genetic characterization of patients with focal epilepsy using a customized targeted resequencing gene panel. Front Neurol 2018; 9: 515
• 74 Wevers RA, Christensen M, Engelke UFH. et al. Functional disruption of pyrimidine nucleoside transporter CNT1 results in a novel inborn error of metabolism with high excretion of uridine and cytidine. J Inherit Metab Dis 2019; 42 (03) 494-500
• 75 Maas RPPWM, Kamsteeg E-J, Mangano S. et al. Benign nocturnal alternating hemiplegia of childhood: a clinical and nomenclatural reappraisal. Eur J Paediatr Neurol 2018; 22 (06) 1110-1117
• 76 Li W, Wang Y, Li B. et al. 16p11.2 deletion in patients with paroxysmal kinesigenic dyskinesia but without intellectual disability. Brain Behav 2018; 8 (11) e01134
• 77 Kim SY, Lee JS, Kim WJ. et al. Paroxysmal dyskinesia in children: from genes to the clinic. J Clin Neurol 2018; 14 (04) 492-497
• 78 Yu H, Jiang S, Wang K. [Identification of two novel PRRT2 gene variants in two children with paroxysmal kinesigenic dyskinesia]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020; 37 (01) 5-7
• 79 Ma H, Feng S, Deng X. et al. A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B. Epilepsia 2018; 59 (08) 1621-1630
• 80 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
• 81 Tanabe Y, Taira T, Shimotake A. et al. [An adult female with proline-rich transmembrane protein 2 related paroxysmal disorders manifesting paroxysmal kinesigenic choreoathetosis and epileptic seizures]. Rinsho Shinkeigaku 2019; 59 (03) 144-148
• 82 Miao P, Feng J, Guo Y. et al. Genotype and phenotype analysis using an epilepsy-associated gene panel in Chinese pediatric epilepsy patients. Clin Genet 2018; 94 (06) 512-520
• 83 Symonds JD, Zuberi SM, Stewart K. et al. Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain 2019; 142 (08) 2303-2318
• 84 El Achkar CM, Rosen Sheidley B, O'Rourke D, Takeoka M, Poduri A. Compound heterozygosity with PRRT2: pushing the phenotypic envelope in genetic epilepsies. Epilepsy Behav Case Rep 2017; 11: 125-128
• 85 Ono S, Yoshiura K, Kinoshita A. et al. Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsions. J Hum Genet 2012; 57 (05) 338-341
• 86 Döring JH, Saffari A, Bast T. et al. The phenotypic spectrum of PRRT2-associated paroxysmal neurologic disorders in childhood. Biomedicines 2020; 8 (11) 456
• 87 Terwindt GM, Ophoff RA, Lindhout D. et al. Partial cosegregation of familial hemiplegic migraine and a benign familial infantile epileptic syndrome. Epilepsia 1997; 38 (08) 915-921
• 88 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
• 89 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
• 90 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
• 91 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
• 92 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361
• 93 Vanmolkot KRJ, Kors EE, Hottenga J-J. et al. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol 2003; 54 (03) 360-366
• 94 Pelzer N, de Vries B, Kamphorst JT. et al. PRRT2 and hemiplegic migraine: a complex association. Neurology 2014; 83 (03) 288-290
• 95 Callenbach PMC, de Coo RFM, Vein AA. et al. Benign familial infantile convulsions: a clinical study of seven Dutch families. Eur J Paediatr Neurol 2002; 6 (05) 269-283
• 96 Seo SY, You SJ. Paroxysmal kinesigenic dyskinesia in a patient with a PRRT2 mutation and centrotemporal spike discharges on electroencephalogram: case report of a 10-year-old girl. Korean J Pediatr 2016; 59 (Suppl. 01) S157-S160
• 97 Torisu H, Watanabe K, Shimojima K. et al. Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes. Brain Dev 2014; 36 (04) 342-345
• 98 Schubert J, Paravidino R, Becker F. et al. PRRT2 mutations are the major cause of benign familial infantile seizures. Hum Mutat 2012; 33 (10) 1439-1443
• 99 Marini C, Conti V, Mei D. et al. PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine. Neurology 2012; 79 (21) 2109-2114
• 100 Barbagallo M, Ruggieri M, Incorpora G. et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
• 101 Pavone P, Praticò AD, Ruggieri M, Falsaperla R. Hypomelanosis of Ito: a round on the frequency and type of epileptic complications. Neurol Sci 2015; 36 (07) 1173-1180
• 102 Lee J, Lee C, Ki CS, Lee J. Determining the best candidates for next-generation sequencing-based gene panel for evaluation of early-onset epilepsy. Mol Genet Genomic Med 2020; 8 (09) e1376
• 103 Okumura A, Shimojima K, Kubota T. et al. PRRT2 mutation in Japanese children with benign infantile epilepsy. Brain Dev 2013; 35 (07) 641-646
• 104 Yang X, Zhang Y, Xu X. et al. Phenotypes and PRRT2 mutations in Chinese families with benign familial infantile epilepsy and infantile convulsions with paroxysmal choreoathetosis. BMC Neurol 2013; 13: 209
• 105 Djémié T, Weckhuysen S, Holmgren P. et al. PRRT2 mutations: exploring the phenotypical boundaries. J Neurol Neurosurg Psychiatry 2014; 85 (04) 462-465
• 106 He Z-W, Qu J, Zhang Y. et al. PRRT2 mutations are related to febrile seizures in epileptic patients. Int J Mol Sci 2014; 15 (12) 23408-23417
• 107 Ishii A, Yasumoto S, Ihara Y. et al. Genetic analysis of PRRT2 for benign infantile epilepsy, infantile convulsions with choreoathetosis syndrome, and benign convulsions with mild gastroenteritis. Brain Dev 2013; 35 (06) 524-530
• 108 Zara F, Specchio N, Striano P. et al. Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance. Epilepsia 2013; 54 (03) 425-436
• 109 Grinton BE, Heron SE, Pelekanos JT. et al. Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 2015; 56 (07) 1071-1080
• 110 Heron SE, Dibbens LM. Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy. J Med Genet 2013; 50 (03) 133-139
• 111 Yang L, You C, Qiu S. et al. Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy. Brain Behav 2020; 10 (05) e01597
• 112 Bruno MK, Hallett M, Gwinn-Hardy K. et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 2004; 63 (12) 2280-2287
• 113 Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutières syndrome. Pediatr Neurol 2001; 24 (04) 300-302
• 114 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
• 115 Weiss LA, Shen Y, Korn JM. et al; Autism Consortium. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 2008; 358 (07) 667-675
• 116 Jacquemont S, Reymond A, Zufferey F. et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 2011; 478 (7367): 97-102
• 117 Guha S, Rees E, Darvasi A. et al; Molecular Genetics of Schizophrenia Consortium, Wellcome Trust Case Control Consortium 2. Implication of a rare deletion at distal 16p11.2 in schizophrenia. JAMA Psychiatry 2013; 70 (03) 253-260
• 118 Reinthaler EM, Lal D, Lebon S. et al; 16p11.2 European Consortium, EPICURE Consortium, EuroEPINOMICS Consortium. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet 2014; 23 (22) 6069-6080
• 119 Hanson E, Bernier R, Porche K. et al; Simons Variation in Individuals Project Consortium. The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population. Biol Psychiatry 2015; 77 (09) 785-793
• 120 Weber A, Köhler A, Hahn A, Neubauer B, Müller U. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome. Neurogenetics 2013; 14 (3-4): 251-253
• 121 Zhang LM, An Y, Pan G. et al. Reduced penetrance of PRRT2 mutation in a chinese family with infantile convulsion and choreoathetosis syndrome. J Child Neurol 2015; 30 (10) 1263-1269
• 122 Etemadikhah M, Niazi A, Wetterberg L, Feuk L. Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes. Sci Rep 2020; 10 (01) 630
• 123 Valente EM, Spacey SD, Wali GM. et al. A second paroxysmal kinesigenic choreoathetosis locus (EKD2) mapping on 16q13-q22.1 indicates a family of genes which give rise to paroxysmal disorders on human chromosome 16. Brain 2000; 123 (Pt 10): 2040-2045
• 124 Spacey SD, Valente E-M, Wali GM. et al. Genetic and clinical heterogeneity in paroxysmal kinesigenic dyskinesia: evidence for a third EKD gene. Mov Disord 2002; 17 (04) 717-725
• 125 Zhou J, Li G, Chen C, Liu D, Xiao B. Familial pure paroxysmal kinesigenic dyskinesia in Han population from the Chinese mainland: a new subtype?. Epilepsy Res 2008; 80 (2-3): 171-179
• 126 Cao L, Huang X-J, Zheng L, Xiao Q, Wang X-J, Chen S-D. Identification of a novel PRRT2 mutation in patients with paroxysmal kinesigenic dyskinesias and c.649dupC as a mutation hot-spot. Parkinsonism Relat Disord 2012; 18 (05) 704-706
• 127 Groffen AJA, Klapwijk T, van Rootselaar A-F, Groen JL, Tijssen MAJ. Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia. J Neurol 2013; 260 (01) 93-99
• 128 Dale RC, Gardiner A, Antony J, Houlden H. Familial PRRT2 mutation with heterogeneous paroxysmal disorders including paroxysmal torticollis and hemiplegic migraine. Dev Med Child Neurol 2012; 54 (10) 958-960
• 129 Dong H, Luo Y, Fan S, Yin B, Weng C, Peng B. Screening gene mutations in chinese patients with benign essential blepharospasm. Front Neurol 2020; 10: 1387
• 130 Vilas D, Marcé-Grau A, Macaya A, Valls-Solé J, Tolosa E. Galloping tongue syndrome in a PRRT2 mutation carrier. Neurol Genet 2019; 5 (06) e377
• 131 Pavone P, Corsello G, Cho SY. et al. PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?. Ital J Pediatr 2019; 45 (01) 159
• 132 Ruggieri M, Rizzo R, Pavone P, Baieli S, Sorge G, Happle R. Temporal triangular alopecia in association with mental retardation and epilepsy in a mother and daughter. Arch Dermatol 2000; 136 (03) 426-427
• 133 Ruggieri M, Iannetti P, Clementi M. et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
• 134 Ruggieri M, Milone P, Pavone P. et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
• 135 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A [phone]
• 136 Pavone P, Praticò AD, Vitaliti G. et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
• 137 Ruggieri M, Praticò AD, Serra A. et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
• 138 Zhao Q, Liu Z, Hu Y. et al. Different experiences of two PRRT2-associated self-limited familial infantile epilepsy. Acta Neurol Belg 2020; 120 (04) 1025-1028
• 139 Latorre A, Bhatia KP. Treatment of paroxysmal dyskinesia. Neurol Clin 2020; 38 (02) 433-447
• 140 De Gusmao CM, Silveira-Moriyama L. Paroxysmal movement disorders - practical update on diagnosis and management. Expert Rev Neurother 2019; 19 (09) 807-822
• 141 Gan J, Cai Q, Galer P. et al. Mapping the knowledge structure and trends of epilepsy genetics over the past decade: a co-word analysis based on medical subject headings terms. Medicine (Baltimore) 2019; 98 (32) e16782
• 142 Méneret A, Gaudebout C, Riant F, Vidailhet M, Depienne C, Roze E. PRRT2 mutations and paroxysmal disorders. Eur J Neurol 2013; 20 (06) 872-878
• 143 Pan G, Zhang L, Zhou S. Clinical features of patients with paroxysmal kinesigenic dyskinesia, mutation screening of PRRT2 and the effects of morning draughts of oxcarbazepine. BMC Pediatr 2019; 19 (01) 439
• 144 Mink JW. Treatment of paroxysmal dyskinesias in children. Curr Treat Options Neurol 2015; 17 (06) 350
• 145 Anheim M, Maillart E, Vuillaumier-Barrot S. et al. Excellent response to acetazolamide in a case of paroxysmal dyskinesias due to GLUT1-deficiency. J Neurol 2011; 258 (02) 316-317
• 146 Hao S-S, Feng Y-H, Zhang G-B, Wang A-P, Wang F, Wang P. Neuropathophysiology of paroxysmal, systemic, and other related movement disorders. Eur Rev Med Pharmacol Sci 2015; 19 (13) 2452-2460
• 147 Méneret A, Roze E. Paroxysmal movement disorders: an update. Rev Neurol (Paris) 2016; 172 (8-9): 433-445
• 148 Mahlknecht P, Limousin P, Foltynie T. Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments. J Neurol 2015; 262 (11) 2583-2595
• 149 Kaufman CB, Mink JW, Schwalb JM. Bilateral deep brain stimulation for treatment of medically refractory paroxysmal nonkinesigenic dyskinesia. J Neurosurg 2010; 112 (04) 847-850
• 150 Suzuki-Muromoto S, Kosaki R, Kosaki K, Kubota M. Familial hemiplegic migraine with a PRRT2 mutation: phenotypic variations and carbamazepine efficacy. Brain Dev 2020; 42 (03) 293-297
• 151 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207