Claudia M Bonardi1, Cyril Mignot2, Jose M Serratosa3, Beatriz G Giraldez4, Raffaella Moretti5, Gabrielle Rudolf6, Chiara Reale7, Pia M Gellert8, Katrine M Johannesen9, Gaetan Lesca10, Carlo A Tassinari11, Elena Gardella12, Rikke S Møller13, Guido Rubboli14. 1. Danish Epilepsy Centre, Dianalund, Denmark; Department of Woman's and Child's Health, University Hospital of Padua, Italy. Electronic address: claudiamaria.bonardi@gmail.com. 2. APHP, Groupe Hospitalier Pitié Salpêtrière, Unité Fonctionnelle de Génétique Médicale, Paris, France; Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France; INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France. Electronic address: cyril.mignot@aphp.fr. 3. Neurology Laboratory and Epilepsy Unit, Department of Neurology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: joseserratosa@me.com. 4. Neurology Laboratory and Epilepsy Unit, Department of Neurology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: BGonzalezG@fjd.es. 5. APHP, Physiology Department, Trousseau Hospital, Paris, France. Electronic address: Raffaella.moretti@aphp.fr. 6. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS U7104, INSERM U1258 Illkirch 67400, France; Department of Neurology, Strasbourg University Hospital, Université de Strasbourg Strasbourg, France. Electronic address: Gabrielle.Rudolf@chru-strasbourg.fr. 7. Danish Epilepsy Centre, Dianalund, Denmark; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. Electronic address: chiara.reale.neu@gmail.com. 8. Danish Epilepsy Centre, Dianalund, Denmark. Electronic address: pmg@filadelfia.dk. 9. Danish Epilepsy Centre, Dianalund, Denmark. Electronic address: kamaa@filadelfia.dk. 10. Hospices Civils de Lyon, Service de Génétique, CHU de Lyon, Lyon, France. Electronic address: gaetan.lesca@chu-lyon.fr. 11. University of Bologna, Bologna, Italy. Electronic address: carloalbertotassinari@gmail.com. 12. Danish Epilepsy Centre, Dianalund, Denmark; Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark. Electronic address: elga@filadelfia.dk. 13. Danish Epilepsy Centre, Dianalund, Denmark; Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark. Electronic address: rimo@filadelfia.dk. 14. Danish Epilepsy Centre, Dianalund, Denmark; University of Copenhagen, Copenhagen, Denmark. Electronic address: guru@filadelfia.dk.
Abstract
OBJECTIVE: To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. METHODS: Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES. RESULTS: Neurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2-6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60-96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood. CONCLUSIONS: Novel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia. SIGNIFICANCE: Our findings expand the phenotypic spectrum of CNKSR2-related ESES.
OBJECTIVE: To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. METHODS: Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES. RESULTS: Neurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2-6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60-96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood. CONCLUSIONS: Novel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia. SIGNIFICANCE: Our findings expand the phenotypic spectrum of CNKSR2-related ESES.
Authors: Eda Erata; Yudong Gao; Alicia M Purkey; Erik J Soderblom; James O McNamara; Scott H Soderling Journal: J Neurosci Date: 2021-09-27 Impact factor: 6.167
Authors: Leigh Ann Higa; Jennifer Wardley; Christopher Wardley; Susan Singh; Timothy Foster; Joseph J Shen Journal: BMC Med Genomics Date: 2021-07-15 Impact factor: 3.063