The primary school student suddenly fainted, why did her heart stop working

Too long to read

An 11-year-old girl suddenly fainted for unknown reasons. Genetic testing diagnosed her with long QT syndrome, a relatively common inherited arrhythmia. Many patients may not have obvious signs before the disease occurs. About 1/3 of patients have normal electrocardiograms and can only be diagnosed through genetic testing. The first symptom of some patients is sudden death, making treatment difficult. Genetic testing is the gold standard for diagnosing long QT syndrome. Through genetic testing, you can:

(1) Early detection, early prevention, accurate diagnosis and accurate treatment of patients;

(2) After identifying the clear genetic factors, it can also help the patient's relatives screen high-risk relatives who are also at risk of the disease, and at the same time identify relatives with a low risk of the disease, so that they no longer have to worry and do not need long-term clinical follow-up;

(3) It can also guide eugenics and prevent future generations from getting sick through prenatal screening and pre-implantation genetic screening.

Case Background

Mr. Zheng is 35 years old, has a stable job, a harmonious family, and two lovely daughters. After the three-child policy was announced, Mr. Zheng and his wife discussed adding another child to their happy big family. But a subsequent phone call broke the tranquility of the family.

It turned out that the eldest daughter Xiaomei, 11 years old, suddenly fainted during a physical education class and was rushed to the hospital. After rushing to the hospital, Mr. Zheng and his wife were told that Xiaomei's electrocardiogram was abnormal. Her QTc was significantly prolonged, reaching 520ms (normal female QTc <460ms), which can basically be judged as long QT syndrome (LQTS). Since LQTS is mostly an autosomal dominant genetic disease, and each patient's relatives have a 50% chance of getting the disease, the doctor recommended that Xiaomei's immediate family members undergo an electrocardiogram examination.

Mr. Zheng couldn't understand it. He thought that he and his wife were both in good health and had never had any heart problems, so it was impossible for them to be sick. Therefore, he was not willing to spend money to check the electrocardiogram for both of them.

But Mr. Zheng was so devoted to his son that he also did an electrocardiogram for Xiaomei's younger sister, Xiaoli. The results showed that Xiaoli's QTc was similar to her sister's, reaching 480ms, also exceeding the normal range. At this point, the doctor could basically determine that Mr. Zheng's family had a family history of LQTS. However, it seemed unreasonable that Mr. Zheng and his wife, who gave birth to two LQTS patients, were both healthy.

Therefore, the doctor suggested that the eldest daughter Xiaomei, as the first patient to be diagnosed in the family, or what is commonly referred to as a proband in medicine, should undergo genetic testing for LQTS-related hereditary arrhythmias.

Test results

Xiaomei's test results showed that she carried a pathogenic mutation in the KCNH2 gene, which can cause LQTS type 2. According to expert consensus, the presence of a clear pathogenic variant can be diagnosed as LQTS, which means that Xiaomei suffers from this inherited arrhythmia disease.

According to expert consensus, the diagnostic criteria for LQTS are shown in the figure

By screening the KCNH2 pathogenic mutation on the younger sister Xiaoli, Mr. Zheng and Mrs. Zheng, it was found that Xiaoli, who already had an abnormal electrocardiogram, and her father Mr. Zheng, who felt that he was healthy, both carried this mutation. Both could be directly diagnosed as type 2 LQTS. Only the mother, Mrs. Zheng, did not carry the mutation and was truly "healthy."

Faced with this result, Mr. Zheng still found it hard to believe. He clearly had no discomfort, so how could he have a genetic disease? This time, Mr. Zheng finally did an electrocardiogram for himself, and found that his QTc was also beyond the normal range for men (QTc < 440ms), reaching 451ms. It turned out that he was not completely "healthy".

A family of four was fine, but three of them were found to be ill. What should he do? Mr. Zheng was at a loss.

Before giving Mr. Zheng advice, let us first understand what LQTS is.

Long QT syndrome, or LQTS, is an ion channel disease. The main electrocardiogram manifestations are QT interval prolongation, T wave abnormalities, and torsades de pointes. The prevalence in the general population is about 1/2500. When LQTS attacks, patients are prone to repeated syncope, convulsions, and even sudden death. For some patients, the first symptom may be sudden death . It is like a time bomb lurking in our bodies, which is extremely dangerous and difficult to treat.

The right picture shows the electrocardiogram of a LQTS patient, showing a prolonged QT interval.

However, not all patients will have a prolonged QT interval on their electrocardiogram. Studies have shown that clinically, about 20-30% of patients have completely normal QT intervals. At this time, genetic testing becomes the only effective method for diagnosing LQTS. Depending on the pathogenic gene, LQTS can be divided into multiple subtypes. The three most common ones are: type 1 LQTS caused by KCNQ1, type 2 LQTS caused by KCNH2, and type 3 LQTS caused by SCN5A. For patients of different subtypes, not only are there differences in the preferred clinical treatment methods, but also in the daily methods of preventing sudden death.

For example, beta-blockers (such as Betaloc), which are generally taken by patients with arrhythmias, are actually the most effective in treating patients with type 1 LQTS, but the effect on patients with type 2 and type 3 LQTS is average. Patients with type 3 LQTS may benefit better from sodium channel blockers (such as lidocaine and propafenone). Potassium supplementation may also be effective for patients with type 1 and type 2 LQTS who have damaged potassium channels.

Factors that induce the onset of different types of LQTS patients

Vigorous exercise is a major risk factor for life-threatening events such as cardiac arrest or sudden death in patients with type 1 LQTS.

Therefore, patients with type 1 LQTS should try to avoid strenuous exercise, especially swimming without company , to prevent drowning due to sudden onset of disease, which can endanger life. Patients with type 2 LQTS are susceptible to sudden sound stimulation and should be wary of sudden alarms, phone rings, explosions, etc. At the same time, patients with type 2 LQTS should explain the situation to those around them and try to avoid activities that may cause surprises or shocks to those around them, which may trigger the disease.

The significance of genetic testing - what to do after diagnosis?

After finding the clear genetic factors, genetic testing can not only assist in clinical accurate diagnosis and treatment, but also help all the patient's immediate family members screen out high-risk relatives who are also at risk of the disease, and provide guidance for eugenics.

In this case, although Xiaomei and Xiaoli could be directly diagnosed through clinical manifestations and electrocardiograms, genetic testing further confirmed that they were type 2 LQTS.

At the same time, Mr. Zheng, who insisted that he was in good health and did not want to have an electrocardiogram, was also a confirmed high-risk relative of carrying a pathogenic mutation identified through genetic testing. It may be more effective for the three of them to take beta-blockers supplemented with potassium.

In addition, genetic testing also identified Mrs. Zheng as someone who does not carry the family's hereditary mutation and has a low risk of developing the disease. She no longer has to worry or require long-term clinical follow-up.

In daily life, Mr. Zheng and his family should turn off the alarm clock and phone ringing to prevent sudden sound stimulation from inducing illness. In addition, Mr. Zheng should inform the school, teachers and classmates of his child's situation so that the teacher can take preventive measures and provide timely treatment to the child in case of an emergency. At the same time, Mr. Zheng and his daughter should try to avoid strenuous exercise, eat a balanced diet, and maintain healthy living habits.

The most important thing is that Mr. Zheng, who has a plan to have children, is worried - can we still have a healthy baby? Because Mr. Zheng carries the LQTS pathogenic mutation, but his wife is normal. At this time, generally speaking, the probability of the couple's next offspring suffering from the disease is 50%. Therefore, the doctor suggested that Mr. Zheng and his wife could consider relevant institutions with assisted reproduction qualifications to artificially choose to have a baby who is no longer sick through prenatal screening or preimplantation genetic diagnosis .

Case summary

After drug treatment and active lifestyle prevention, Xiaomei did not fall ill again, and Mr. Zheng's family's lives gradually returned to normal.

Like most inherited cardiovascular diseases, LQTS also has an insidious onset. About one-third of patients have completely normal electrocardiograms before the disease occurs, and the diagnosis can only be confirmed by detecting pathogenic mutations through genetic testing. At the same time, the first symptom of some LQTS patients is sudden death. If it is not discovered in advance, it is difficult to save . Only genetic testing can help the examinee conduct risk assessment early, take effective preventive measures, and avoid tragedy. Therefore, all clinical guidelines and expert consensus recommend genetic testing for patients suspected or diagnosed with LQTS.

Through genetic testing, you can:

**(1) Assisting in clear diagnosis and precise treatment: **Assisting in clear diagnosis of potential patients who have not yet developed the disease or are in the early stages of the disease. Early detection can lead to early prevention. It also helps in precise treatment of confirmed patients.

**(2) Guiding screening of high-risk relatives: **After finding clear genetic factors, we can also help the patient's relatives screen high-risk relatives who are also at risk of the disease. High-risk relatives can consult a doctor in a timely manner according to the specific situation and undergo regular physical examinations. At the same time, we can identify relatives with low risk of the disease, so that they no longer need to worry and do not need long-term clinical follow-up;

**(3) Guiding eugenics: **Most patients with hereditary cardiovascular diseases have a high probability of their offspring also suffering from the same disease. Therefore, genetic testing can also guide eugenics and prevent offspring from getting sick again through prenatal screening and pre-implantation genetic screening.

To learn more about cardiovascular health, please follow Dr. Ma’s Heart Lectures