The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).

An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute.

Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011).

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.

Atrial standstill or silent atrium is a rare condition presenting with the absence of electrical and mechanical activity in the atria. It presents with the absence of P waves, bradycardia, and wide QRS complex in the electrocardiogram.

An abnormality in which the cardiac ventricles depolarize too early as a result of an abnormality of cardiac conduction pathways such as an accessory pathway.

Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate.\n\nPeople with Down syndrome often have a characteristic facial appearance that includes a flattened appearance to the face, outside corners of the eyes that point upward (upslanting palpebral fissures), small ears, a short neck, and a tongue that tends to stick out of the mouth. Affected individuals may have a variety of birth defects. Many people with Down syndrome have small hands and feet and a single crease across the palms of the hands. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common.\n\nIndividuals with Down syndrome have an increased risk of developing several medical conditions. These include gastroesophageal reflux, which is a backflow of acidic stomach contents into the esophagus, and celiac disease, which is an intolerance of a wheat protein called gluten. About 15 percent of people with Down syndrome have an underactive thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. Individuals with Down syndrome also have an increased risk of hearing and vision problems. Additionally, a small percentage of children with Down syndrome develop cancer of blood-forming cells (leukemia).\n\nDelayed development and behavioral problems are often reported in children with Down syndrome. Affected individuals can have growth problems and their speech and language develop later and more slowly than in children without Down syndrome. Additionally, speech may be difficult to understand in individuals with Down syndrome. Behavioral issues can include attention problems, obsessive/compulsive behavior, and stubbornness or tantrums. A small percentage of people with Down syndrome are also diagnosed with developmental conditions called autism spectrum disorders, which affect communication and social interaction.\n\nPeople with Down syndrome often experience a gradual decline in thinking ability (cognition) as they age, usually starting around age 50. Down syndrome is also associated with an increased risk of developing Alzheimer's disease, a brain disorder that results in a gradual loss of memory, judgment, and ability to function. Approximately half of adults with Down syndrome develop Alzheimer's disease. Although Alzheimer's disease is usually a disorder that occurs in older adults, people with Down syndrome commonly develop this condition earlier, in their fifties or sixties.

Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011).

Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the MYH7 gene.

The constitutional deletion of chromosome 1p36 results in a syndrome with multiple congenital anomalies and mental retardation (Shapira et al., 1997). Monosomy 1p36 is the most common terminal deletion syndrome in humans, occurring in 1 in 5,000 births (Shaffer and Lupski, 2000; Heilstedt et al., 2003). See also neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH; 616975), which shows overlapping features and is caused by heterozygous mutation in the RERE gene (605226) on proximal chromosome 1p36. See also Radio-Tartaglia syndrome (RATARS; 619312), caused by mutation in the SPEN gene (613484) on chromosome 1p36, which shows overlapping features.

Dilated cardiomyopathy-1Y (CMD1Y) is characterized by severe progressive cardiac failure, resulting in death in the third to sixth decades of life in some patients. Electron microscopy shows an abnormal sarcomere structure (Olson et al., 2001). In left ventricular noncompaction-9 (LVNC9), patients may present with cardiac failure or may be asymptomatic. Echocardiography shows noncompaction of the apex and midventricular wall of the left ventricle (Probst et al., 2011). Some patients also exhibit Ebstein anomaly of the tricuspid valve (Kelle et al., 2016) and some have mitral valve insufficiency (Nijak et al., 2018).

FREM1 autosomal recessive disorders include Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR syndrome), and isolated congenital anomalies of kidney and urinary tract (CAKUT). MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and renal malformations (e.g., renal agenesis, renal dysplasia). Typically the eye manifestations of MOTA syndrome are absent. FREM1-CAKUT was identified in one individual with bilateral vesicoureteral reflux (VUR) and a second individual with VUR and renal hypodysplasia.

CMD2E is characterized by neonatal or early childhood onset of dilated cardiomyopathy, with rapid progression to cardiac failure and death unless patients undergo cardiac transplantation (Vasilescu et al., 2018; Jones et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see 115200.