In this episode we will discuss
Timothy Syndrome with our guest Courtney Waller.
Timothy syndrome is a rare genetic disorder that affects the heart and several other organs. The most obvious manifestation is the abnormally long repolarization (QT interval) in the heart that predisposes patients to cardiac arrhythmias and sudden cardiac death. Unlike other forms of long QT syndrome, patients with Timothy syndrome also present with cardiac malformations, thickening of the cardiac walls (cardiac hypertrophy) and enlargement of the heart (cardiac dilatation).
Timothy syndrome is also associated with abnormalities of fingers or toes that are fused together through webbed skin between the digits (cutaneous syndactyly), specific facial features, a weakened immune system, developmental delays and episodes of low levels of sugar in the blood (hypoglycemia).
Timothy syndrome is caused by DNA changes (mutations) in the CACNA1C gene that provides instructions for making calcium channels in the heart. These channels allow calcium to enter cardiac cells. Since these calcium channels are not only present in the heart but also in many other organs, symptoms of Timothy syndrome are widespread. Use of beta blockers, pacemakers, and implant of cardiac defibrillators can be used to reduce arrhythmias and prevent cardiac arrest. The other symptoms should be managed through close surveillance and avoiding triggering factors.
Signs & Symptoms
One defining feature of Timothy syndrome is a long QT interval on an electrocardiogram (EKG). The QT interval is the time required for the heart to complete ventricular contraction and relaxation. The delayed return to resting state predisposes the heart to develop ventricular arrhythmias and functional heart blocks. These heart arrhythmias can be very rapid and impair the ability of the heart to pump blood to the brain: for these reasons patients may experience fainting episodes that are the manifestation of arrhythmias and should prompt hospitalization. Anesthesia may also trigger arrhythmias, and for this reason surgeons and the anesthesiologists should be aware that the patient has Timothy syndrome and discuss with the electrophysiologist the management of the patient and his/her monitoring during surgery.
It is important to know that not all individuals with Timothy syndrome present with cutaneous syndactyly. The diagnosis of Timothy syndrome in these patients can be established only with genetic testing. In the patients that present with syndactyly, it involves the index, middle, ring, and little fingers, as well as toes two and three. The syndactyly may be on one side of the body or both, and can be between two, three, or four fingers.
Timothy syndrome is also associated with specific facial characteristics. These include low-set ears, a lower nasal bridge, a small upper jaw, baldness at birth and for the first two years of life, followed by thin hair, and small, widely spaced teeth with a predisposition to cavities. Other findings include frequent infections, rigid joints and occasional episodes of low blood sugar (hypoglycemia) that may lead to fainting and if untreated may cause death.
Children with Timothy syndrome may also have developmental delays, including autism spectrum disorders that can involve difficulty communicating, socializing, or making correct movements. Seizures, strokes, and blindness can also occur as a result of developmental delays in those with Timothy syndrome.
PodcastDX and NORD gratefully acknowledges Emily Norton, NORD Editorial Intern from the University of Connecticut, and Silvia G Priori, MD, PhD, Professor of Cardiology, University of Pavia, Director of Cardiology at ICS Maugeri Hospital, Pavia Italy, for assistance in the preparation of this report.
Synonyms of Timothy Syndrome
long QT syndrome with syndactyly
long QT syndrome type 8
Courtney Waller is the co-Founder of Timothy Syndrome Alliance, and mom to a 5yo daughter with the condition.
She has been a legislative advocate for the rare disease community for the past five years. Primarily working on legislation by state. She is the founder and principal of Policy Served Rare, a patient centered think tank focusing on policy that focuses on health and mental health care for the rare disease community.
Twitter: @Timothy Syndrome
Facebook: Policy Served Rare @policyservedrare