ALPK3

Clinical Characteristics

Most patients with mutations in both copies of ALPK3 present with severe cardiomyopathy prenatally or within the first years of life. The cardiomyopathy is characterized by enlargement and – at a later stage – thickening of the heart muscle. Although left ventricular hypertrophy is more common, hypertrophy of both ventricles can also occur. This may lead to heart failure. ALPK3-cardiomyopathy may result in intrauterine or early neonatal death. Some patients may need an implantable cardioverter defibrillator or heart transplant.

The majority of patients display postnatal growth retardation. About half of the patients have musculoskeletal abnormalities, including scoliosis (abnormal curvature of the spine), webbed neck and joint contractures (abnormal shortening or stiffening of joints). Less common features include developmental delay and hypotonia (decreased muscle tone). Many patients have cleft palate or facial dysmorphisms, including hypertelorism (widely-spaced eyes) and low-set ears.

The occurrence and severity of additional clinical features is variable among individuals with ALPK3– cardiomyopathy.