000			02872 am a22003373u 4500
042			_adc
100	1	0	_aField, Ella _eauthor _91214
700	1	0	_aNorrish, Gabrielle _eauthor _91215
700	1	0	_aAcquaah, Vanessa _eauthor _91216
700	1	0	_aDady, Kathleen _eauthor _91217
700	1	0	_aCicerchia, Marcos _eauthor _91218
700	1	0	_aOchoa, Juan Pablo _eauthor _91219
700	1	0	_aSyrris, Petros _eauthor _91220
700	1	0	_aMcLeod, Karen _eauthor _91221
700	1	0	_aMcGowan, Ruth _eauthor _91222
700	1	0	_aFell, Hannah _eauthor _91223
700	1	0	_aLopes, Luis R _eauthor _91224
700	1	0	_aCervi, Elena _eauthor _91225
700	1	0	_aKaski, Juan Pablo _eauthor _91226
245	0	0	_aCardiac myosin binding protein-C variants in paediatric-onset hypertrophic cardiomyopathy: natural history and clinical outcomes
260			_c2022-08.
500			_a/pmc/articles/PMC7613139/
500			_a/pubmed/34400558
520			_aBACKGROUND: Variants in the cardiac myosin-binding protein C gene (MYBPC3) are a common cause of hypertrophic cardiomyopathy (HCM) in adults and have been associated with late-onset disease, but there are limited data on their role in paediatric-onset HCM. The objective of this study was to describe natural history and clinical outcomes in a large cohort of children with HCM and pathogenic/likely pathogenic (P/LP) MYBPC3 variants. METHODS AND RESULTS: Longitudinal data from 62 consecutive patients diagnosed with HCM under 18 years of age and carrying at least one P/LP MYBPC3 variant were collected from a single specialist referral centre. The primary patient outcome was a major adverse cardiac event (MACE). Median age at diagnosis was 10 (IQR: 2-14) years, with twelve patients (19.4%) diagnosed in infancy. Forty-seven (75%) were male and 31 (50%) were probands.Median length of follow-up was 3.1 (IQR: 1.6-6.9) years. Nine patients (14.5%) experienced a MACE during follow-up and five (8%) died. Twenty patients (32.3%) had evidence of ventricular arrhythmia, including 6 patients (9.7%) presenting with out-of-hospital cardiac arrest. Five year freedom from MACE for those with a single or two MYBPC3 variants was 95.2% (95% CI: 78.6-98.5) and 68.4% (95% CI: 40.6-88.9), respectively (hazard ratio 4.65, 95% CI: 1.16-18.66, p=0.03). CONCLUSIONS: MYBPC3 variants can cause childhood-onset disease, which is frequently associated with life-threatening ventricular arrhythmia. Clinical outcomes in this cohort vary substantially from aetiologically and genetically mixed paediatric HCM cohorts described previously, highlighting the importance of identifying specific genetic subtypes for clinical management of childhood HCM.
540			_a
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nJ Med Genet
856	4	1	_uhttp://dx.doi.org/10.1136/jmedgenet-2021-107774 _zConnect to this object online.
999			_c1749 _d1749