ALPK3 and cardiac hypertrophy: Heterozygous ALPK3 loss-of-function variants are also estimated to cause ~1.5% to 2.5% of unexplained ventricular hypertrophy that occurs in adults.6,9 These heterozygous variants likely have variable and age-dependent penetrance, because obligate carrier relatives of critically ill infants with recessive ALPK3 cardiomyopathy often have no cardiac disease.6