Timothy syndrome is a genetic condition caused by disease-causing genetic changes in the CACNA1C gene. Timothy syndrome may affect many parts of the body especially the heart, nervous system (brain and nerves) and physical development. It is considered a type of heart rhythm condition called long QT syndrome.

Timothy syndrome can be categorised into three subtypes, depending on the symptoms:

• Timothy syndrome type 1 (ORPHA:595098)
• Timothy syndrome type 2 (ORPHA:595105)
• Atypical Timothy syndrome (ORPHA:595109)

Below on this page is some information about this condition as well as links to useful resources for Australians living with a rare disease.

Synonyms: TS, LQT8, long QT syndrome type 8, long QT syndrome-syndactyly syndrome.

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:65283 Timothy syndrome

ICD-11: BC65.0 Long QT syndrome

Rare diseases typically display a high level of symptom complexity. There is often a wide range of symptoms and the symptoms may vary between individuals in terms of its presentation, severity, duration and impact.

Please speak to your medical team to learn more about the symptoms of this condition.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Timothy syndrome is genetic condition. It is caused by disease-causing genetic changes (variants) in the CACNA1C gene on chromosome 12. CACNA1C gene produces a protein that forms part of a calcium channel which is expressed in many parts of the body. These calcium channels play a key role in maintaining heartbeat and communication and signaling between neurons (nerve cells).

For most individuals with Timothy syndrome, their genetic variant in CACNA1C gene occurs randomly (de novo) prior to birth.

In some cases, Timothy syndrome can be inherited through germline mosaicism, where a parent has the disease-causing genetic variants in their germ cells (egg or sperm cells) that are passed on to the child in pregnancy. More information about germline mosaicism can be found at Centre for Genetics Education: Mosaicism.

All individuals have two copies (alleles) of the CACNA1C gene – one on each chromosome that is inherited from each parent. Timothy syndrome is an autosomal dominant condition, which means that having a genetic variant in just one of the CACNA1C gene copies can result in Timothy syndrome. More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

A timely diagnosis is critical for better patient outcomes, the provision of the best possible care and treatment options, access to services and support, increased reproductive confidence and the ability to participate in clinical trials.

Please speak to your medical team to learn more about the available diagnostic pathways for this condition.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the treatment of Timothy syndrome may include general practitioners (GP), cardiologists, dietitians, endocrinologists, gastroenterologists, neurologists, paediatricians, pulmonologists. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

If you know of any relevant care guidelines, please let us know via the Contribute page.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

If you know of any relevant emergency management guidelines or information relevant to emergency care, please let us know via the Contribute page.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

We are not aware of any rare disease organisations for Timothy syndrome in Australia. If you are aware of any Australian organisations, please let us know via the Contribute page.

International Organisation:

Timothy Syndrome Alliance (United Kingdom)

Website: https://timothysyndrome.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Timothy syndrome varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on Timothy syndrome can be found at:

• Better Health Channel: Long QT syndrome
• Unique: Timothy syndrome CACNA1C
• Genetic and Rare Diseases (GARD) Information Center: Timothy syndrome
• National Organization for Rare Disorders (NORD): Timothy Syndrome

GeneReviews®: CACNA1C-Related Disorders

Online Mendelian Inheritance in Man, OMIM®: #618447 Long QT syndrome; LQT8

Orphanet: Timothy syndrome

Human Phenotype Ontology (HPO): Timothy syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. If you would like to see more information added to this page, please reach out via the Contact form. If you would like to share relevant resources for this condition, please visit the Contribute page.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.