Dr Shivanee Shah
Genetic testing can go a long way in determining the treatment and outcome of a disease in a patient. Here is a case of a 19-year old girl who presented with a history of seizures at the neurological department at Amrita Hospital, Kochi, but turned out to have a heart condition. Genetic testing helped identify the exact mutations which dictated her treatment modality.
This patient had a history of seizures, where during each episode she was reported to become unresponsive with seizure-like activity while falling asleep. These episodes were short lived; during her first attack, she was only unresponsive for a brief period, and did not receive any medical attention. However, during her subsequent episodes, she had up-rolling of eyeballs along with unresponsiveness and was brought to the hospital. Brain CT was normal, and she was diagnosed with epilepsy. She was started on sodium valproate as the anti-epileptic drug, but since she also complained of a vague chest pain, she was referred to the cardiology department for a consultation. Here she underwent an ECG, which showed a prolonged QT interval of 506 milliseconds (QTc), which is markedly above-normal. The working diagnosis was that of ‘long QT syndrome’.
Long QT syndrome may occur in response to certain medications. However, in the majority of the cases, it is an inherited autosomal dominant syndrome typically caused due to a mutation in one of 17 cardiac ion channel proteins. Symptoms include transient loss of consciousness, seizures and irregular beating of the heart which prevents circulation of blood to the brain and can result in loss of consciousness. About 75% of the inherited long QT syndrome is caused due to mutations in 3 ion channel proteins that can result in one of three types of long QT syndrome — type 1, 2 or 3. Type 1 (LQ1) is caused due to a disruption of the potassium ion channel activity and the consequent disruption of the heart’s electrical activity. Arrhythmias in such cases are typically triggered due to physical exertion and such episodes tend to stop without medical intervention and are less likely to be fatal. Type 2 (LQ2) is caused due to insufficient potassium ion activity in the heart and can be triggered due to emotional stress and loud noises. While types 1 and 2 are due to mutations in potassium ion channels, type 3 (LQ3) is due to mutations in sodium ion channels and occurs due to low levels of sodium flow in the heart, leading to arrhythmia. Such episodes are typically triggered during sleep or rest and are more likely to be fatal. Molecular testing is an important aspect of identifying the type of long QT syndrome and can help in confirming clinical diagnosis as well as in guiding treatment strategy. LQT1 and LQT2 are caused due to mutations in the potassium channel genes, KCNQ1and KCNH2, respectively, while LQT3 is caused by mutations in a sodium channel gene, SCN5A.
‘For accurate treatment modality, we recommended our patient to undergo molecular testing,’ said Dr. Hisham Ahamed, Associate Professor in Cardiology, Amrita Institute of Medical Sciences and Research, Kochi. Her family agreed, and her blood sample was sent to MedGenome Labs, Bengaluru, for a cardiac channelopathy panel. This panel can identify mutations in cardiac ion channels that may result in any abnormal variation in QT interval. The genetic panel results showed that the patient had a mutation in KCNH2and was therefore diagnosed as having type 2 long QT syndrome.
While type 1 patients show good response to using medications such as beta-blockers, type 2 patients generally do not respond as well to such treatment and are typically advised for implantable devices such as an implantable cardioverter defibrillator (ICD), if they are considered high-risk. Until the patient’s family could agree for such a procedure, the patient was started on beta-blockers, since a subset of type 2 patients can benefit from such medication as well. The beta-blocker therapy has been effective thus far for this patient. Two years later, she has experienced no further episodes and her heart rhythm has returned to normal on its own. ‘’Our patient has been fortunate that the beta-blocker treatment has worked for her, although we would like to see the patient follow through on the recommended ICD implant,” says Dr. Ahamed. ‘’The lesson learnt from this case is that ECG should be performed in young individuals with a history of seizures to rule out cardiac concerns.”
Dr Shivanee Shah