Condition AZ: t

Also known as: TS


Timothy Syndrome (TS) is a rare, multi-system condition caused by genetic changes in the L-Type calcium channel gene named CACNA1C. Individuals with Timothy Syndrome are affected to differing degrees and most have been found to have an abnormal heart function as well as developmental delays.


Medical text written July 2020 by Katherine Timothy and Timothy Syndrome Alliance, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

Most individuals with Timothy Syndrome present with:

  • Abnormal cardiac function (specifically a prolonged QT interval, arrhythmias) and cardiac structural abnormalities [Patent ductus arteriosus (PDA), Tetralogy of Fallot (ToF), Atrial septal defect(ASD,) Ventricular septal defect (VSD), etc.]
  • Neuronal developmental delays including physical, social and mental difficulties [autism, attention deficit disorder (ADD,) attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), schizophrenia, etc.]
  • Immunodeficiencies (frequent respiratory, bronchial and laryngeal infections)
  • Endocrinological dysfunction (including pancreatic, adrenal and thyroid concerns)
  • Smooth muscle affectedness including gastrointestinal issues (constipation being one of the greatest concerns)
  • Skeletal muscle affectedness including hypotonia(low muscle tone)
  • Facial anomalies, hand and foot syndactyly ( fused digits)
  • Dental, skin, eye, hair anomalies

Some individuals with Timothy Syndrome present with:

  • Hypoglycemia (unusual blood sugar level fluctuations, particularly associated with infections and fasting).
  • Seizures
  • Hypothermia (an unusually low body temperature)

Children with Timothy syndrome are usually developmentally delayed, with most having moderate learning difficulties and special educational needs. Significant speech delays are common, receptive speech is generally more advanced compared to expressive speech.

Timothy Syndrome children typically show delays in reaching physical milestones such as walking, running, jumping and skipping. Social development is generally impaired, shyness often predominates with a common preference for solitude; however, in some cases the TS child can seem overly friendly. 

What are the causes?

Timothy Syndrome is caused by different genetic changes sprinkled throughout the CACNA1C gene.  Three different types of TS have been characterized according to their specific mutational changes.

  • TS 1 is often identified at birth if an infant presents with serious cardiac concerns and syndactyly (conjoined fingers and toes).  Genetic results identify a specific amino acid change of G406R, in exon 8A of CACNA1C. 
  • TS 2 is often identified at birth with greater cardiac concerns than TS1, although no syndactyly or other physical anomalies there is often hypotonia.  Genetic results identify a specific amino acid change of G406R, NOT in exon 8A but in exon 8.
  • TS3 Othe rCACNA1C changes present with similar TS multi-system health concerns. These are referred to as Atypical Timothy syndrome(ATS). 

Not all CACNA1C mutational changes cause multi-system disorders, some changes seemingly cause only singular cardiac function abnormalities [i.e. Long QT syndromeonly, Short QT syndrome(SQT), Catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada Syndrome] or other single system anomalies. These identified CACNA1C changes would be named according to the disorder they most closely relate to.  

Additionally, some CACNA1C changes might be considered harmless in that the change would not alter or adversely affect the function of the CACNA1C calcium channel  (polymorphism).

How is it diagnosed?

Timothy syndrome is anautosomal(meaning not gender specific)dominant(meaning the characteristic would dominate) genetic condition. Timothy Syndrome is confirmed by genetic testing.

How is it treated?

Management of the condition involves a variety of medical, educational and social support. There is no cure for the condition. Individuals will need to be managed by a multidisciplinary team of specialists, including a cardiac specialist, who can help support their medical, educational and social care needs.

Inheritance patterns and prenatal diagnosis

Inheritance patterns

Most cases are sporadic(de novo)during fertilization or the development of the fetus. It is possible for parents to carry the molecular change (mosaicism) and thus unknowingly pass on the variant to the child. A clinical geneticist would be able to advise your family. 

Prenatal diagnosis

For couples who already have a child with Timothy syndrome seeking reassurance, or for pregnancy in someone affected by Timothy syndrome, prenatal diagnosis by PGD (Preimplantation Genetic Diagnosis) is possible.

Is there support?

Timothy Syndrome Alliance (TSA)


Timothy Syndrome Alliance (TSA) is a Registered Charity in England and Wales no. 1185523. They aim to provide support to all those affected by Timothy Syndrome and deleterious CACNA1C gene changes, their friends, families and carers. They provide information, raise awareness of the condition and aim to bring families together. They also have different Facebook Groups to support families and professionals. 

Group details added July 2020