CACNA1C Gene

Timothy syndrome is a rare disorder that primarily affects the heart but can affect many other areas of the body, including the fingers and toes, teeth, nervous system, and immune system. The severity of this condition varies among affected individuals, although it is often life-threatening due to the heart problems.

Timothy syndrome is characterized by a heart condition called long QT syndrome, which causes the heart (cardiac) muscle to take longer than usual to recharge between beats. This abnormality in the heart's electrical system can cause severe abnormalities of the heart rhythm (arrhythmias), which can lead to sudden death. Some people with Timothy syndrome are also born with structural heart defects (cardiomyopathy) that affect the heart's ability to pump blood effectively. As a result of these serious heart problems, many people with Timothy syndrome live only into childhood. In about 80 percent of cases of Timothy syndrome, the cause of death is a severe form of arrhythmia called ventricular tachycardia, in which the lower chambers of the heart (the ventricles) beat abnormally fast, often leading to cardiac arrest and sudden death.

Timothy syndrome is also characterized by webbing or fusion of the skin between some fingers or toes (cutaneous syndactyly). About half of affected people have distinctive facial features such as a flattened nasal bridge, low-set ears, a small upper jaw, and a thin upper lip. Children with this condition have small, misplaced teeth and frequent cavities (dental caries). Additional signs and symptoms of Timothy syndrome can include baldness at birth, frequent infections, episodes of low blood sugar (hypoglycemia), and an abnormally low body temperature (hypothermia).

Researchers have found that many children with Timothy syndrome have the characteristic features of autism or similar conditions known as autistic spectrum disorders. Affected children tend to have impaired communication and socialization skills, as well as delayed development of speech and language. Other nervous system abnormalities that can occur in Timothy syndrome include intellectual disability and recurrent seizures (epilepsy); some affected individuals have photosensitive epilepsy, in which seizures are triggered by flashing lights.

Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to irregular heartbeats in the heart's lower chambers (ventricles), which is an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.

Brugada syndrome usually becomes apparent in adulthood, although it can develop any time throughout life. Signs and symptoms related to arrhythmias, including sudden death, can occur from early infancy to late adulthood. Sudden death typically occurs around age 40. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than 1 year. SIDS is characterized by sudden and unexplained death, usually during sleep.

Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.