Background: To compare outcome and cardiac pathology between patients with Noonan syndrome (N-HCM) and sarcomere protein-associated (S-HCM) childhood onset hypertrophic cardiomyopathy (HCM).Methods: Clinical data were recorded from medical charts. Primary endpoint was survival. Secondary endpoints were survival without hospitalization, without intervention or without arrhythmic events.Functional clinical status and results from genetic testing, imaging, electrocardiographic (ECG) studies, cardiopulmonary exercise testing (CPET) and histopathology were compared between groups.Results: Childhood HCM was diagnosed in 29 N-HCM and 34 S-HCM patients. Follow-up time was greater than 10 years in more than half of all patients. Mortality was below 7% and not different between groups. Children with N-HCM presented at a younger age and there was less time of survival without hospitalization for heart failure or intervention in N-HCM compared to S-HCM patients. Clinical functional status improved over time in N-HCM patients. On long-term follow-up, left ventricular posterior wall thickness indexed to body surface area decreased in N-HCM and increased in S-HCM patients. There was a trend to lower risk for severe arrhythmic events in N-HCM patients and only S-HCM individuals received an implantable cardioverter-defibrillator. There were no differences between groups in ventricular function, ECG and CPET parameters. Myocardial fibrosis as assessed by histopathology of myocardial specimens and cardiovascular magnetic resonance with late gadolinium enhancement or T1 mapping was present in both groups.Conclusions: When compared to S-HCM patients, children with N-HCM have increased morbidity during early disease course, but favorable long-term outcome with low mortality, stagnation of myocardial hypertrophy, and low risk for malignant arrhythmias.

Surgical septal myectomy can be performed safely during infancy with favourable perioperative and long-term clinical outcome but with a trend towards a higher reoperation rate later in life.

Hypertrophic cardiomyopathy (HCM) is associated with adverse left ventricular (LV) remodeling causing dysfunction and malignant arrhythmias. Severely affected patients present with disease onset during childhood and sudden cardiac death risk (SCD) stratification is of the highest importance in this cohort. This study aimed to investigate genotype–phenotype association regarding clinical outcome and disease progression in pediatric onset HCM. Medical charts from forty-nine patients with pediatric HCM who had undergone genetic testing were reviewed for retrospective analysis. Demographic, clinical, transthoracic echocardiographic, electrocardiographic, long-term electrocardiogram, cardiopulmonary exercise test, cardiac magnetic resonance, and medication data were recorded. Childhood onset HCM was diagnosed in 29 males and 20 females. Median age at last follow-up was 18.7 years (range 2.6–51.7 years) with a median follow-up time since diagnosis of 8.5 years (range 0.2–38.0 years). Comparison of patients carrying mutations in distinct genes and comparison of genotype-negative with genotype-positive individuals, revealed no differences in functional classification, LV morphology, hypertrophy, systolic and diastolic function, fibrosis and cardiac medication. Patients with compound mutations had a significantly higher risk for major arrhythmic events than a single-mutation carrier. No association between affected genes and disease severity or progression was identified in this cohort.