Timothy Syndrome

Gene: CACNA1C   

Protein: Voltage-dependent L-type calcium channel subunit alpha-1C

Clinical characteristics:

• Prolonged QT interval
• Other EKG abnormalities
  • 2:1 atrioventricular block
  • Macroscopic T-wave alternans
• Syndactyly
  • Bilateral cutaneous syndactyly of toes two and three
  • Unilateral or bilateral cutaneous syndactyly variably involving fingers two, three, four, and five
• Congenital heart defects
• Dysmorphic facial features
• Thin scalp hair and poor tooth enamel
• Neurologic features
  • Hypotonia
  • Developmental delay
  • Autism
  • Seizures

Inheritance pattern:

• Autosomal dominant
• Typically de novo; germline mosaicism has been reported

What this test can tell us:
Testing is performed by sequencing exons 8 and 8A (alternatively transcribed coding exons) and the surrounding intronic regions of the CACNA1C gene. This will detect point mutations, small deletions, and small insertions. It will not detect a partial or whole gene deletion or duplication.

A negative test result does not rule out a genetic cause of long QT syndrome (LQTS). Other genes are known to be associated with LQTS and this test will only detect mutations associated with Timothy syndrome. This test will not detect mutations in other regions of the gene, such as those associated with Brugada syndrome.

Sample requirements: Draw one or two 4cc tubes of blood in EDTA/ purple top tube (minimum of 1-2 cc for infants)

Turnaround time:   10-14 business days

CPT codes and cost: 
83891 (x1)       83898 (x2)       83904 (x4)       83912 (x1)             $250

Timothy Syndrome Testing Packet

Additional Resources:

• Gene Review 
• OMIM Entries