Timothy syndrome

Timothy syndrome is a multi-system disorder that affects the heart, hands, face, and neurodevelopment. It is caused by pathogenic variants in the CACNA1C gene, which plays an important role in calcium signaling in multiple tissues. The condition presents in early life with distinct cardiac, physical, and neurodevelopmental features and is considered very rare, affecting fewer than 1 in 1,000,000 individuals. Its highly variable presentation means that while some individuals exhibit prominent heart rhythm disturbances and facial dysmorphism, others may have milder manifestations.

Individuals with Timothy syndrome typically present with a prolonged QT interval, which is an obligate finding, along with other cardiac abnormalities such as atrioventricular block and bradycardia. Characteristic physical features include cutaneous syndactyly (webbed fingers and toes) and microdontia, as well as distinctive facial characteristics such as a flattened nasal bridge, low-set ears, a small upper jaw, and a thin upper lip. Neurodevelopmental aspects are also notable, with many individuals exhibiting features on the autism spectrum, intellectual disability, and global developmental delays. Not all individuals experience all features, and severity varies considerably.

Timothy syndrome is caused by pathogenic variants in the CACNA1C gene, which is essential for proper calcium channel function in the heart and brain. Disruption of this gene affects electrical signaling and muscle contraction, contributing to the cardiac and neurodevelopmental features seen in the condition. The syndrome is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene can cause the disorder. Genetic counseling is recommended for families to better understand the inheritance pattern and implications for future family planning.

Currently, management of Timothy syndrome focuses on supportive care and symptom management, with treatment tailored to the individual’s specific needs. There are no FDA-approved treatments available, so care typically involves a multidisciplinary team addressing cardiac, developmental, and other medical concerns. Regular surveillance is an essential part of long-term care, helping to identify potential complications at an early stage. Families are encouraged to discuss treatment options with their healthcare team and to consider genetic counseling for guidance on management and family planning.

The clinical course of Timothy syndrome is highly variable, with outcomes differing widely between individuals. With current standards of care, many affected individuals can live into adulthood, although the severity of cardiac and developmental issues may impact quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition for ongoing support and updated management strategies.