Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study

被引：47

作者：

Trivisano, Marina ^{[1
,2
]}

Pietrafusa, Nicola ^{[1
]}

Terracciano, Alessandra ^{[3
]}

Marini, Carla ^{[4
]}

Mei, Davide ^{[4
]}

Darra, Francesca ^{[5
]}

Accorsi, Patrizia ^{[6
]}

Battaglia, Domenica ^{[7
]}

Caffi, Lorella ^{[8
]}

Canevini, Maria P. ^{[9
,10
]}

Cappelletti, Simona ^{[11
]}

Cesaroni, Elisabetta ^{[12
]}

de Palma, Luca ^{[1
]}

Costa, Paola ^{[13
]}

Cusmai, Raffaella ^{[1
]}

Giordano, Lucio ^{[6
]}

Ferrari, Annarita ^{[14
]}

Freri, Elena ^{[15
]}

Fusco, Lucia ^{[1
]}

Granata, Tiziana

Martino, Tommaso ^{[2
]}

Mastrangelo, Massimo ^{[16
]}

Bova, Stefania M. ^{[16
]}

Parmeggiani, Lucio ^{[17
]}

Ragona, Francesca ^{[15
]}

Sicca, Federico ^{[14
]}

Striano, Pasquale ^{[18
]}

Specchio, Luigi M. ^{[2
]}

Tondo, Ilaria ^{[11
]}

Zambrelli, Elena ^{[9
,10
]}

Zamponi, Nelia ^{[12
]}

Zanus, Caterina ^{[13
]}

Boniver, Clementina ^{[19
]}

Vecchi, Marilena ^{[19
]}

Avolio, Carlo ^{[2
]}

Dalla Bernardina, Bernardo ^{[5
]}

Bertini, Enrico ^{[20
]}

Guerrini, Renzo ^{[4
]}

Vigevano, Federico ^{[1
]}

Specchio, Nicola ^{[1
]}

机构：

[1] Bambino Gesu Pediat Hosp, Dept Neurosci, Neurol Unit, IRCCS, Rome, Italy

[2] Univ Foggia, Clin Nervous Syst Dis, Foggia, Italy

[3] Bambino Gesu Pediat Hosp, IRCCS, Lab Med Genet, Rome, Italy

[4] Univ Florence, Childrens Hosp Meyer, Pediat Neurol Unit & Labs, Florence, Italy

[5] Univ Verona, Dept Life & Reprod Sci, Verona, Italy

[6] Civilian Hosp, Child Neuropsychiat Unit, Brescia, Italy

[7] Catholic Univ, Child Neurol & Psychiat, Rome, Italy

[8] Univ Bergamo, Neuropsychiat Unit, Bergamo, Italy

[9] San Paolo Hosp, Epilepsy Ctr, Milan, Italy

[10] Univ Milan, Dept Hlth Sci, Milan, Italy

[11] Bambino Gesu Pediat Hosp, IRCCS, Dept Neurosci, Unit Clin Psychol, Rome, Italy

[12] Univ Ancona, Child Neuropsychiat Unit, Ancona, Italy

[13] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy

[14] IRCCS Stella Maris Fdn, Clin Neurophysiol Lab, Dept Dev Neurosci, Pisa, Italy

[15] IRCCS Fdn, Carlo Besta Neurol Inst, Dept Pediat Neurosci, Milan, Italy

[16] Vittore Buzzi Hosp, ASST Fatebenefratelli Sacco, Pediat Neurol Unit, Milan, Italy

[17] Reg Hosp Bolzano, Dept Neuropediat, Bolzano, Italy

[18] Univ Genoa, Pediat Neurol & Muscular Dis Unit, Dept Neurosci, Rehabil,Ophthalmol,Genet,Maternal,Child Hlth,G Ga, Genoa, Italy

[19] Univ Hosp Padua, Dept Womens & Childrens Hlth, Child Neurol & Clin Neurophysiol Unit, Padua, Italy

[20] Bambino Gesu Pediat Hosp, IRCCS, Dept Neurosci, Unit Neuromuscular & Neurodegenerat Disorders, Rome, Italy

来源：

EPILEPSIA | 2018年 / 59卷 / 12期

关键词：

epileptic encephalopathy; focal epilepsy; genetic epilepsy; genotype-phenotype correlation; PCDH19; PROTOCADHERIN; 19; PCDH19; MUTATIONS; FEMALES; ENCEPHALOPATHY; EXPRESSION; SPECTRUM; PROFILE;

D O I：

10.1111/epi.14600

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors. Methods Results We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for >= 2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). Significance We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.

引用

页码：2260 / 2271

页数：12

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