Timothy syndrome

Autosomal dominant - en

Timothy syndrome is a rare genetic disorder characterized by severe cardiac arrhythmias, syndactyly, and autistic features. It is caused by mutations in the CACNA1C gene, which encodes a subunit of the L-type calcium channel. This syndrome is named after Dr. Katherine W. Timothy, who first described the condition.

Presentation

Individuals with Timothy syndrome typically present with a range of symptoms, including:

• Prolonged QT interval on ECG
• Syndactyly (webbing of the fingers and toes)
• Facial dysmorphism
• Developmental delay
• Autistic features
• Immune deficiency
• Hypoglycemia

Genetics

Timothy syndrome is caused by mutations in the CACNA1C gene located on chromosome 12. This gene encodes the alpha-1C subunit of the L-type calcium channel, which is crucial for the proper functioning of cardiac muscle, smooth muscle, and neurons. The most common mutation associated with Timothy syndrome is a substitution of glycine for arginine at position 406 (G406R).

Diagnosis

Diagnosis of Timothy syndrome is based on clinical features and confirmed by genetic testing. ECG findings typically show a prolonged QT interval, which can lead to life-threatening arrhythmias. Genetic testing can identify mutations in the CACNA1C gene.

Management

Management of Timothy syndrome involves a multidisciplinary approach, including:

• Cardiology for management of arrhythmias
• Orthopedic surgery for correction of syndactyly
• Neurology and psychiatry for developmental and behavioral issues
• Immunology for immune deficiencies

Prognosis

The prognosis for individuals with Timothy syndrome is generally poor due to the high risk of cardiac arrhythmias and sudden cardiac death. Early diagnosis and management are crucial to improve outcomes.

Related Pages

• Long QT syndrome
• CACNA1C
• Genetic disorder
• Cardiac arrhythmia
• Autism spectrum disorder