of sequencing data has underscored the importance of consistently reassessing our understanding of single-nucleotide variants.84 The pitfalls in assessing genetic testing in HCM are also a reflection of the gaps in understanding of the biochemical basis of HCM disease, which remains incompletely understood The studies to date have focused on increased calcium sensitivity and handling,85–88 sodium currents,85,89 and energetics, which lead to increased force generation with impaired relaxation.90–94 This has led to studies examining the role of medications that may be the underlying pathophysiology of HCM via the modification of power generation,94–96 calcium handling,97 and late sodium inhibition.85,98 Ongoing or recently completed studies are also focused on the role of medical therapy in altering disease progression by reducing the activation of transforming growth factor β (TGF-β)99 and oxidative stress (e.g., the HALT-HCM [hypertrophic regression with N-acetylcysteine in HCM] study) Rasopathies Noonan syndrome (NS) with and without multiple lentigines (previously known as LEOPARD syndrome), NS with anagen hair, Costello syndrome,100 and cardiocutaneous syndrome are collectively known as RASopathies They are characterized by perturbations in the RAS/mitogen-activated protein kinase signaling pathway and commonly involve cardiac malformations, including HCM (Table 61.1) Table 61.1 Selected Syndromes and Diseases Associated With Cardiomyopathy and Their Typical Patterns of Presentation Syndrome/Disease Typical Age at Presentation History and Physical Examination Barth syndrome