{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:10:08Z","timestamp":1759691408254,"version":"build-2065373602"},"reference-count":11,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","award":["GN, EF, JPK"],"award-info":[{"award-number":["GN, EF, JPK"]}],"id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Max's Foundation","award":["Support JK and EF"],"award-info":[{"award-number":["Support JK and EF"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC-NIHR CARP MR\/T024062\/1"],"award-info":[{"award-number":["MRC-NIHR CARP MR\/T024062\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,12,20]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>Up to 20% of children with sarcomeric hypertrophic cardiomyopathy (HCM) have disease-causing variants in genes coding for thin-filament proteins. However, data on genotype-phenotype correlations for thin-filament disease are limited. This study describes the natural history and outcomes of children with thin-filament-associated HCM and compares it to thick-filament-associated disease.<\/jats:p>\n               <jats:p>Longitudinal data were collected from 40 children under 18 years with a disease-causing variant in a thin-filament protein from a single quaternary referral centre. Twenty-one (female n=6, 35.5%) were diagnosed with HCM at a median age of 13.0 years (IQR 8.3\u201314.0). Over a median follow-up of 5.0 years (IQR 4.0\u20138.5), three (14.3%) experienced one or more major adverse cardiac events (MACE) (two patients had an out-of-hospital arrest and eight appropriate implantable cardiac defibrillator (ICD) therapies in three patients). One gene carrier died suddenly at age 9 years. Compared with those with thick-filament disease, children with thin-filament variants more commonly experienced non-sustained ventricular tachycardia [NSVT; n=6 (28.6%) vs n=14 (10.8%), p=0.024] or underwent ICD insertion (thin, n=13 (61.9%) vs thick, n=50 (38.5%), p=0.040). However, there was no difference in the incidence of MACE (thin 2.47\/100 pt years (95% CI 0.80 to 7.66) vs thick 3.63\/100 pt years (95% CI 2.25 to 5.84)) or an arrhythmic event (thin 1.65\/100 pt years (95%\u2009CI 0.41 to 6.58) vs thick 2.55\/100 pt years (95%\u2009CI 1.45 to 4.48), p value 0.43).<\/jats:p>\n               <jats:p>This study suggests that adverse events in thin-filament disease are predominantly arrhythmic and may occur in the absence of hypertrophy, but overall short-term outcomes do not differ significantly from thick-filament disease.<\/jats:p>","DOI":"10.1136\/jmg-2023-109684","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T13:30:24Z","timestamp":1706707824000},"page":"420-422","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Childhood-onset hypertrophic cardiomyopathy caused by thin-filament sarcomeric variants"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2064-237X","authenticated-orcid":false,"given":"Gabrielle","family":"Norrish","sequence":"first","affiliation":[{"name":"Centre for Paediatric Inherited and Rare Cardiovascular Disease, Institute of Cardiovascular Science, University College London, London, UK"},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisa","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2763","authenticated-orcid":false,"given":"Ella","family":"Field","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited and Rare Cardiovascular Disease, Institute of Cardiovascular Science, University College London, London, UK"},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Cervi","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited and Rare Cardiovascular Disease, Institute of Cardiovascular Science, University College London, London, UK"},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0014-9927","authenticated-orcid":false,"given":"Juan Pablo","family":"Kaski","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited and Rare Cardiovascular Disease, Institute of Cardiovascular Science, University College London, London, UK"},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"2025100511291288000_61.5.420.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075463"},{"key":"2025100511291288000_61.5.420.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(96)00530-X"},{"key":"2025100511291288000_61.5.420.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.09.059"},{"key":"2025100511291288000_61.5.420.4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.959973"},{"key":"2025100511291288000_61.5.420.5","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1001\/jamacardio.2018.0789","article-title":"Long-term outcomes of pediatric-onset hypertrophic cardiomyopathy and age-specific risk factors for lethal arrhythmic events","volume":"3","author":"Maurizi","year":"2018","journal-title":"JAMA Cardiol"},{"key":"2025100511291288000_61.5.420.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107774"},{"key":"2025100511291288000_61.5.420.7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1161\/CIRCGEN.123.004118","article-title":"Childhood hypertrophic cardiomyopathy caused by beta-myosin heavy chain variants is associated with a more obstructive but less arrhythmogenic phenotype than myosin-binding protein C disease","volume":"16","author":"Norrish","year":"2023","journal-title":"Circ Genom Precis Med"},{"key":"2025100511291288000_61.5.420.8","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2025100511291288000_61.5.420.9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028895"},{"key":"2025100511291288000_61.5.420.10","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1093\/eurheartj\/ehab148","article-title":"Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy","volume":"42","author":"Marston","year":"2021","journal-title":"Eur Heart J"},{"key":"2025100511291288000_61.5.420.11","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1177\/2047487317702519","article-title":"Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: a systematic review and meta-analysis","volume":"24","author":"Norrish","year":"2017","journal-title":"Eur J Prev Cardiol"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2023-109684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T18:29:18Z","timestamp":1759688958000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2023-109684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":11,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,4,19]]},"published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1136\/jmg-2023-109684"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2023-109684","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[2024,1,31]]}}}