TANGO2: A Rare but Important Mutation

Area of Science:

• Genetics and Molecular Biology
• Cardiology
• Pediatrics

Background:

• A 7-year-old boy presented with post-viral myositis, rhabdomyolysis, and hepatitis.
• He was later readmitted for seizure-like activity and diagnosed with polymorphic ventricular tachycardia due to QT prolongation and severe hypothyroidism.

Observation:

• Initial treatment with transvenous atrial pacing and levothyroxine normalized QTc interval.
• Genetic testing revealed a KCNQ1 mutation, suggesting Long QT Syndrome (LQTS) type 1.
• Subsequent neurodegeneration and seizures led to further genetic testing, identifying pathogenic variants in TANGO2.

Findings:

• TANGO2 deficiency provides a unifying explanation for the patient's complex presentation, including myositis, rhabdomyolysis, hypothyroidism, and arrhythmias, often triggered by viral illness.
• The TANGO2 gene is frequently omitted from standard arrhythmia and cardiomyopathy genetic panels.
• TANGO2 deficiency is a rare disorder that may be overlooked by cardiologists and electrophysiologists due to its infrequent presentation with arrhythmias.

Implications:

• This case highlights the importance of considering TANGO2 deficiency in pediatric patients with unexplained multisystemic illness, particularly those involving cardiac arrhythmias and metabolic derangements.
• The findings underscore the need for broader genetic testing panels to include genes like TANGO2 for comprehensive diagnosis of rare genetic disorders.
• Management strategies and diagnostic caveats presented can assist clinicians in identifying and treating TANGO2 deficiency effectively.