Genetic testing for Short QT syndrome (SQTS) (R130)

Background information

SQTS predisposes to cardiac arrhythmia, syncope and sudden death with a highly variable age of onset. Originally, SQTS was viewed as a benign finding but it has been show that there is a cumulative probability of cardiac arrest by the fifth decade of 40 percent. The estimated prevalence is unknown.

Although SQTS is genetically heterogeneous if a strong family history is present then detection rate is thought to be up to 15-25 percent.

Currently there are four genes on the panel which are all inherited in an autosomal dominant manner. Around 15 percent of cases are accounted for by variants in KCNH2 whereas missense variants in KCNJ2, KCNQ1, and CACNA1C have all been found in only a few familial cases.

KCNJ2 is also associated with other cardiac channelopathies, mainly Andersen-Tawil syndrome (ATS) but more rarely LQTS and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). In KCNH2 and KCNQ1 are more commonly reported in individuals with LQTS.

Testing strategy

Clinically affected probands:

R130 - Singleton analysis of four genes.

Targeted analysis for known / previously reported familial variants:

• Family testing in clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)
• Diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
• Segregation studies in affected family members to aid variant interpretation (R375)
• Prenatal diagnosis for families with a pathogenic or likely pathogenic variant identified (R240 and R321 Maternal cell contamination)

Target reporting times

• 42 calendar days for diagnostic screening of affected individuals
• 42 calendar days for diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
  
• 14 calendar days for presymptomatic testing of clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)

Turnaround times for genetic / genomic testing

Sample requirements and referring samples

All non NHSE referrals should be accompanied by a completed referral form.

Requesting specialties:

• Cardiology
• Clinical Genetics
• Paediatrics
• Electrophysiology
• Pathology
• Coroners

Specimen requirements and referring samples

Price list for non NHSE referrals (pdf)