Timothy Syndrome is one of the many syndromes causing long QT and is referred to as ‘Long QT Syndrome Type 8’. It was first described by Timothy et al in 2004 and is a rare genetic disorder.

It has a broad spectrum of characteristics which include:

• cardiac arrhythmias (prolonged QT/QTc interval, bradycardia, 2:1 AV block,
  T-wave alternans)
• congenital cardiac defects (PDA, PFO, VSD, tetralogy of Fallot, HOCM)
• syndactaly (variably involving the index, middle, ring and little fingers)
• bilateral cutaneous syndactaly of the second and third toes

The following features have also been described:

• craniofacial characteristics
• immunodeficiency
• neurodevelopment delay
• a tendency to hypoglycaemia
• autistic spectrum disorders

Two forms of Timothy Syndrome exist. Type 1 includes all of the characteristic features. Type 2 causes a more severe form of long QT syndrome (LQTS) but does not appear to cause the fusion of interdigital skin.

All cases of Timothy Syndrome arise from a mutation if the CACNA1C gene which is located on the short arm of Chromosome 12. This gene encodes the L-type Ca(v)1.2 calcium channel protein. The gene mutation causes a reduction in the inactivation of the calcium channels during the plateau phase of the cardiac action potential. The result is that the calcium channels never close properly allowing excess calcium to influx into the cell. This in turn leads to prolongation of the plateau phase and thus the QT/QTc interval. The clinical implications of this are: an increased risk of spontaneous ventricular tachyarrhythmia, especially tornadoes de points (TdP), and sudden death.

A recent study identified five variants in the CACNA1C gene associated with long QT syndrome, however not all were associated with the phenotypical manifestations of Timothy Syndrome. Timothy Syndrome is inherited in an autosomal dominant manner; most cases, however, arise as spontaneous mutations rather than from direct parental inheritance.

Tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycaemia. The life expectancy of a patient with Timothy Syndrome is 2.5 years. But as patients may also live much longer, anaesthetists need to provide anaesthesia to patients of a variety of ages.