Khemika K Sudnawa, Alexa Geltzeiler, Cara H Kanner, Kyle Zreibe, Nicolò Pini, Celia Tam, Robert J Fee, Sean Calamia, Emily Callejo, Holli Sharples, Catherine E Serianni, Michela Fagiolini, Ellen Hanson, Jacqueline Montes, April Levin, Wendy K Chung
{"title":"mapk8ip3相关神经发育障碍的综合临床特征、纵向适应功能和脑电图活动","authors":"Khemika K Sudnawa, Alexa Geltzeiler, Cara H Kanner, Kyle Zreibe, Nicolò Pini, Celia Tam, Robert J Fee, Sean Calamia, Emily Callejo, Holli Sharples, Catherine E Serianni, Michela Fagiolini, Ellen Hanson, Jacqueline Montes, April Levin, Wendy K Chung","doi":"10.1111/cge.70032","DOIUrl":null,"url":null,"abstract":"<p><p>Mitogen-activated protein kinase 8-interacting protein 3-related neurodevelopmental disorder (MAPK8IP3-related NDD) results from heterozygous pathogenic or likely pathogenic variants in MAPK8IP3. We report on 32 individuals (median age 7.5 years, range 1.3-22.0), all of whom had heterozygous pathogenic/likely pathogenic MAPK8IP3 variants, including missense (62.5%) and predicted loss-of-function (LOF) variants (34.4%). Common symptoms included cognitive impairment, hypotonia, motor difficulties, strabismus, microcephaly, and attention deficits. Corpus callosum thinning was reported in 62.1%. Nearly all individuals walked independently but demonstrated slower gait speed and a wider base of support compared to controls. The mean DAS-II General Conceptual Ability score was 62.5 ± 26.5. EEG analysis suggested a trend toward lower power accentuated frequency compared to typically developing individuals. Missense variants were associated with more severe symptoms than LOF variants. This study provides valuable insights into the clinical characteristics, patient management, and preparation for future clinical trials.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comprehensive Clinical Characteristics, Longitudinal Adaptive Functioning, and Electroencephalogram Activity in MAPK8IP3-Related Neurodevelopmental Disorder.\",\"authors\":\"Khemika K Sudnawa, Alexa Geltzeiler, Cara H Kanner, Kyle Zreibe, Nicolò Pini, Celia Tam, Robert J Fee, Sean Calamia, Emily Callejo, Holli Sharples, Catherine E Serianni, Michela Fagiolini, Ellen Hanson, Jacqueline Montes, April Levin, Wendy K Chung\",\"doi\":\"10.1111/cge.70032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mitogen-activated protein kinase 8-interacting protein 3-related neurodevelopmental disorder (MAPK8IP3-related NDD) results from heterozygous pathogenic or likely pathogenic variants in MAPK8IP3. We report on 32 individuals (median age 7.5 years, range 1.3-22.0), all of whom had heterozygous pathogenic/likely pathogenic MAPK8IP3 variants, including missense (62.5%) and predicted loss-of-function (LOF) variants (34.4%). Common symptoms included cognitive impairment, hypotonia, motor difficulties, strabismus, microcephaly, and attention deficits. Corpus callosum thinning was reported in 62.1%. Nearly all individuals walked independently but demonstrated slower gait speed and a wider base of support compared to controls. The mean DAS-II General Conceptual Ability score was 62.5 ± 26.5. EEG analysis suggested a trend toward lower power accentuated frequency compared to typically developing individuals. Missense variants were associated with more severe symptoms than LOF variants. This study provides valuable insights into the clinical characteristics, patient management, and preparation for future clinical trials.</p>\",\"PeriodicalId\":10354,\"journal\":{\"name\":\"Clinical Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cge.70032\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.70032","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Comprehensive Clinical Characteristics, Longitudinal Adaptive Functioning, and Electroencephalogram Activity in MAPK8IP3-Related Neurodevelopmental Disorder.
Mitogen-activated protein kinase 8-interacting protein 3-related neurodevelopmental disorder (MAPK8IP3-related NDD) results from heterozygous pathogenic or likely pathogenic variants in MAPK8IP3. We report on 32 individuals (median age 7.5 years, range 1.3-22.0), all of whom had heterozygous pathogenic/likely pathogenic MAPK8IP3 variants, including missense (62.5%) and predicted loss-of-function (LOF) variants (34.4%). Common symptoms included cognitive impairment, hypotonia, motor difficulties, strabismus, microcephaly, and attention deficits. Corpus callosum thinning was reported in 62.1%. Nearly all individuals walked independently but demonstrated slower gait speed and a wider base of support compared to controls. The mean DAS-II General Conceptual Ability score was 62.5 ± 26.5. EEG analysis suggested a trend toward lower power accentuated frequency compared to typically developing individuals. Missense variants were associated with more severe symptoms than LOF variants. This study provides valuable insights into the clinical characteristics, patient management, and preparation for future clinical trials.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease