U.S. flag

An official website of the United States government

GTR Home > Conditions/Phenotypes > Timothy syndrome

Timothy syndrome

Synonyms
Long QT syndrome with syndactyly
Modes of inheritance
Autosomal dominant inheritance (Orphanet)

Summary

Excerpted from the GeneReview: CACNA1C-Related Disorders
The first identified CACNA1C-related disorder, referred to as Timothy syndrome, consists of the combination of prolonged QT interval, autism, and cardiovascular malformation with syndactyly of the fingers and toes. Infrequent findings also include developmental and speech delay, seizures, and recurrent infections. With increased availability of molecular genetic testing, a wider spectrum of pathogenic variants and clinical findings associated with CACNA1C-related disorders has been recognized. Because CACNA1C is associated with calcium channel function, all individuals with a pathogenic variant in this gene are at risk for cardiac arrhythmia of a specific type. The clinical manifestations of a CACNA1C-related disorder include three phenotypes: Timothy syndrome with or without syndactyly. QT prolongation (QTc >480 ms) and arrhythmias in the absence of other syndromic features. Short QT syndrome (QTc <350 ms) or Brugada syndrome with short QT interval. These three phenotypes can be separated into two broad categories on the basis of the functional consequences of the pathogenic variants in CACNA1C: QT prolongation with or without a Timothy syndrome-associated phenotype associated with pathogenic variants inducing a gain of function at the cellular level (i.e., increased calcium current). Short QT interval with or without Brugada syndrome EKG pattern associated with pathogenic variants causing loss of function (i.e., reduced calcium current).
Full text of GeneReview (by section):
Summary
GeneReview Scope
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Carlo Napolitano
Katherine W Timothy
Raffaella Bloise
view full author information

Available tests

78 tests are in the database for this condition.

Check Related conditions for additional relevant tests.

Clinical tests (78 available)

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: CACH2, CACN2, CACNA1C-IT2, CACNL1A1, CCHL1A1, CaV1.2, LQT8, NEDHLSS, TS, TS. LQT8, CACNA1C
    Summary: calcium voltage-gated channel subunit alpha1 C

Clinical features

Help
Imported from Human Phenotype Ontology (HPO)

Show allHide all

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.