RESUMEN
BACKGROUND: Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined. METHODS: Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2-related neurodevelopmental disorder. RESULTS: We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p.(Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain. CONCLUSION: We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management.
Asunto(s)
Discapacidad Intelectual , Trastornos del Neurodesarrollo , Ubiquitina-Proteína Ligasas , Genotipo , Humanos , Discapacidad Intelectual/genética , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Trastornos del Neurodesarrollo/genética , Fenotipo , Convulsiones/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: The individual healthcare plan (IHP) was implemented in schools in France in 2003 to improve management of allergic children. Our objectives were to assess the practical aspects of IHP (excluding asthma) and allergic reactions occurring at school. METHODS: Prospective study conducted in the North Department (France) during the 2015/2016 school year. Two questionnaires were developed: one for the school doctors (n = 67) and one for the school principals (n = 2372). RESULTS: Data from 336 (25%) of the 1325 IHPs (0.24% of children) were collected (mean age: 8 years; food allergy [FA]: 94% [peanut = 44%, nuts = 54%], venom: 4%). Wide variations in emergency kit (EK) medications were observed: antihistamines (84%), oral corticosteroids (79%), adrenaline auto-injectors (70%), and inhaled bronchodilators (65%). Six hundred and seventy (28%) school principals' responses, representing 81% of all IHPs, were analyzed. A total of 1935 EKs were stored (mean: 2.8/school), one or more with adrenaline, by 213 (32%) schools: in the class room (33%), the nursery (14%), or the principal's office (10%). Sixty, mainly, mild-to-moderate allergic reactions (adrenaline injection: 2) occurred in 44 schools (0.09/school/year), in children with previously undocumented allergy in 50%. FA was highly suspected in 92%. CONCLUSION: Individual healthcare plan is mainly implemented for FA. Anaphylaxis remains rare in the school setting, and FA is often a suspected cause of reaction. Staff training should be improved. Application of the recommendations regarding the content and accessibility of EK and a widespread emergency action plan is needed.