RESUMEN
ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype-phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype-phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.
Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas Co-Represoras/genética , Proteínas de Unión al ADN/genética , Epilepsia/diagnóstico , Epilepsia/genética , Variación Genética , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/genética , Fenotipo , Adolescente , Adulto , Alelos , Sustitución de Aminoácidos , Niño , Preescolar , Bases de Datos Factuales , Electroencefalografía , Epilepsia/terapia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
Children and young people (CYP) with neurodevelopmental disorders (NDDs) may be particularly vulnerable to adverse mental health effects due to the COVID-19 pandemic. We conducted a cross-sectional U.K. parent-reported study from 2nd April-2nd June 2020, using the Strengths and Difficulties Questionnaire. CYP with NDDs (n = 371), compared to neurotypical controls, had a higher prevalence of emotional symptoms (42% vs. 15%) and conduct problems (28% vs. 9%), and fewer prosocial behaviours (54% vs. 22%). All groups had worse emotional symptoms than pre-COVID groups, and those with attention-deficit/hyperactivity disorder showed inflated conduct problems, while those with autism spectrum disorder exhibited decreased prosocial behaviours. Females with ASD had higher emotional symptoms compared to males. CYP with NDDs, and those without, showed higher levels of parent-reported mental health problems than comparable cohorts pre-COVID-19.