Roseline Caumes1, Odile Boespflug-Tanguy2, Nathalie Villeneuve3, Laetitia Lambert4, Catherine Delanoe1, Bruno Leheup5, Nadia Bahi-Buisson6, Stéphane Auvin7. 1. APHP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, 75019 Paris, France. 2. APHP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, 75019 Paris, France; Inserm, U676, 75019 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, INSERM UMR676, 75019 Paris, France. 3. APHM, CINAPSE, Pediatric Neurology Department, Timone Children Hospital, Marseille, France. 4. Maternité régionale de Nancy Unité Génétique Clinique, 54000 Nancy, France; CHU de Nancy Pole Enfant, Unité neuropédiatrie, Service de Médecine Infantile I, Centre de Référence Maladies Rares CLADEst, Service de Médecine Infantile III et Génétique Clinique, 54500 Vandoeuvre les Nancy, France; Université Lorraine, EA 4368, 54500 Vandoeuvre les Nancy, France. 5. CHU de Nancy Pole Enfant, Centre de Référence Maladies Rares CLADEst, Service de Médecine Infantile III et Génétique Clinique, 54500 Vandoeuvre les Nancy, France; Université Lorraine, EA 4368, 54500 Vandoeuvre les Nancy, France. 6. Service de Neurologie pédiatrique, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker, Paris, France; Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), Paris, France; Inserm, U1016, Paris, France. 7. APHP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, 75019 Paris, France; Inserm, U676, 75019 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, INSERM UMR676, 75019 Paris, France. Electronic address: auvin@invivo.edu.
Abstract
UNLABELLED: Mutation of the X-linked methyl CpG binding protein 2 (MECP2) has been first identified as the cause of Rett syndrome. More recently, MECP2 gene duplication syndrome has been identified in males. The MECP2 duplication syndrome is characterized by severe mental retardation, infantile hypotonia, progressive spasticity and recurrent infections. Epileptic seizures are inconstant but poorly described. The aim of the study is to describe the electroclinical features of epilepsy in MECP2 duplication patients in order to refine the epilepsy phenotype and its evolution. METHODS: We conducted a retrospective study in four child neurology departments in France. Eight boys with a MECP2 gene duplication and epilepsy were retrospectively studied. We evaluated both clinical and electroencephalographic data before seizure onset, at seizure onset and during the follow-up. RESULTS: The patients started seizures at the median age of 6 years (range: 2.5-17 years). Half exhibits late onset epileptic spasms while the other exhibit either focal epilepsy or unclassified generalized epilepsy. Before seizure onset, EEGs were abnormal in all patients showing a slowing of the background or a normal background with fast activities, while EEG performed in epileptic patients, showed a slowing of the background in 6/8 and localized slow or sharp waves in 7/8. Most patients (6/8) have evolved to drug resistant epilepsy. CONCLUSION: Although late onset epileptic spasms are common in patients with MECP2 duplication, no specific electroclinical phenotype emerges, probably due to genetic heterogeneity of the syndrome. Further studies are needed to individualize specific epileptic subtype in larger cohort of patients.
UNLABELLED: Mutation of the X-linked methyl CpG binding protein 2 (MECP2) has been first identified as the cause of Rett syndrome. More recently, MECP2 gene duplication syndrome has been identified in males. The MECP2 duplication syndrome is characterized by severe mental retardation, infantile hypotonia, progressive spasticity and recurrent infections. Epilepticseizures are inconstant but poorly described. The aim of the study is to describe the electroclinical features of epilepsy in MECP2 duplication patients in order to refine the epilepsy phenotype and its evolution. METHODS: We conducted a retrospective study in four child neurology departments in France. Eight boys with a MECP2 gene duplication and epilepsy were retrospectively studied. We evaluated both clinical and electroencephalographic data before seizure onset, at seizure onset and during the follow-up. RESULTS: The patients started seizures at the median age of 6 years (range: 2.5-17 years). Half exhibits late onset epilepticspasms while the other exhibit either focal epilepsy or unclassified generalized epilepsy. Before seizure onset, EEGs were abnormal in all patients showing a slowing of the background or a normal background with fast activities, while EEG performed in epilepticpatients, showed a slowing of the background in 6/8 and localized slow or sharp waves in 7/8. Most patients (6/8) have evolved to drug resistant epilepsy. CONCLUSION: Although late onset epilepticspasms are common in patients with MECP2 duplication, no specific electroclinical phenotype emerges, probably due to genetic heterogeneity of the syndrome. Further studies are needed to individualize specific epileptic subtype in larger cohort of patients.
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