@genetic-counselor
Genetic Counselor
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In most families, long QT syndrome follows autosomal dominant inheritance. This means a single changed copy of the gene is enough to cause the condition. We all carry two copies of each gene — one from each parent. A person with long QT syndrome has one working copy and one changed copy.
Each time that person has a child, there is a 1-in-2 chance of passing on the changed copy, and a 1-in-2 chance of passing on the working copy. This chance is the same for every pregnancy, and for sons and daughters alike. Almost everyone with long QT syndrome has inherited it from a parent; new variants that start in the affected person are uncommon.
An important feature is that the same variant can affect family members very differently. This is called variable expression and reduced penetrance. About 1-in-4 people who carry a disease-causing variant have a normal electrocardiogram. They may never have symptoms, but they still carry some risk — especially with certain medicines or low potassium — and can still pass the variant to their children. This is why a normal electrocardiogram alone cannot rule out long QT syndrome in a relative.
A rare recessive form: Jervell and Lange-Nielsen syndrome When a child inherits a changed copy of KCNQ1 (or, less often, KCNE1) from both parents, they have Jervell and Lange-Nielsen syndrome. These children are born with profound hearing loss and a much longer QT interval, and have a higher risk of heart events. When both parents carry a variant, each pregnancy has a 1-in-4 chance of this form. It is more common in communities where marriage between relatives is traditional, which is relevant to some families in India.
Once the family’s variant is known, “cascade testing” is recommended for parents, brothers, sisters, and children:
Genetic testing for the known family variant A simple, accurate blood or saliva test that tells relatives whether they carry the variant.
Electrocardiogram and heart review Recommended for all first-degree relatives, whether or not they have genetic testing.
Testing children from birth Children can be tested from birth, because heart events can happen in childhood and treatment is effective.Testing during pregnancy or before pregnancy (for example, with embryo testing during in vitro fertilisation) is possible when the family variant is known, and is best discussed with a genetic counselor.
Many people with long QT syndrome never have symptoms. Others first come to attention after a fainting episode, or when a relative is diagnosed. When symptoms do happen, they are caused by a sudden, abnormal heart rhythm, and they often have a recognisable trigger.
Fainting without warning Sudden collapse, often during physical effort, strong emotion, or a sudden fright. This is different from ordinary fainting, which usually has a warning feeling first.
Seizure-like episodes A brief period of jerking movements during a faint can be mistaken for epilepsy. Some people with long QT syndrome are first misdiagnosed with a seizure disorder.
Sudden cardiac arrest Rarely, the first sign is a cardiac arrest, or an unexplained sudden death in a young family member, including drowning in a strong swimmer.The triggers often point to the type:
Type 1 (KCNQ1) Events usually happen during exercise, especially swimming.
Type 2 (KCNH2) Events are linked to sudden loud noises (an alarm clock or ringing phone), emotional stress, and the months after childbirth.
Type 3 (SCN5A) Events tend to happen during rest or sleep, when the heart rate is slow.Diagnosis starts with a resting electrocardiogram. Doctors measure the “corrected QT interval,” which adjusts the reading for heart rate. A corrected QT interval of 480 milliseconds or more on repeated tracings is considered diagnostic. Borderline readings are combined with symptoms and family history in a scoring system (the Schwartz score). An exercise test or a 24-hour heart monitor may help, because some changes only show when the heart rate speeds up or slows down.
Genetic testing with a gene panel finds the cause in about 75–80% of people with a clear clinical diagnosis. International guidelines recommend genetic testing and genetic counseling for everyone diagnosed, because the gene result helps guide treatment and allows accurate testing of relatives.
Long QT syndrome is an inherited condition that affects the heart’s electrical system. The heart muscle itself is usually normal in structure. What is different is the way the heart “recharges” between beats.
Every heartbeat is triggered by an electrical signal. After each beat, the heart cells need a brief moment to reset before the next beat. On an electrocardiogram (the heart tracing done with stickers on the chest), this reset period is measured as the “QT interval” – the distance between two points on the tracing named Q and T. In long QT syndrome, this reset takes longer than it should. You can think of it like a camera flash that needs extra time to recharge; if the next signal arrives before it is ready, the heart can fall into a chaotic, fast rhythm. This dangerous rhythm can cause sudden fainting, seizure-like episodes, or, rarely, cardiac arrest.
The reset depends on tiny gates, called ion channels, in the walls of heart cells. These gates let potassium, sodium, and calcium move in and out in a carefully timed way. Long QT syndrome happens when a change (a pathogenic variant) in a gene that builds one of these gates makes it work less well — or, in some types, work too much.
Three genes account for most cases where a genetic cause is found:
KCNQ1 (type 1) Makes a potassium gate. Accounts for about 30–35% of genetically confirmed cases.
KCNH2 (type 2) Makes a different potassium gate. Accounts for about 25–30% of cases.
SCN5A (type 3) Makes a sodium gate. Accounts for about 5–10% of cases.An international expert review in 2020 found strong evidence for only these three genes in typical long QT syndrome. A few other genes (CALM1, CALM2, CALM3, TRDN, and CACNA1C) cause rarer, often more severe forms that usually appear in infancy or early childhood. Long QT syndrome affects about 1 in every 2,000 to 2,500 people worldwide.
First trimester screening is a set of tests done early in pregnancy, usually between 11 and 14 weeks, to estimate the chance that the baby has certain chromosome conditions.
Chromosomes are the packages that carry our DNA. Most people have 46 chromosomes in each cell, arranged in 23 pairs. Sometimes a baby has an extra copy of one chromosome, which is called a trisomy. First trimester screening looks mainly for three of these:• Down syndrome (trisomy 21) An extra copy of chromosome 21. It is the most common chromosome condition in babies born alive. It causes learning disability of varying degree, and some babies have heart or bowel differences.
• Edwards syndrome (trisomy 18) An extra copy of chromosome 18. It causes serious problems with the heart and other organs, and many pregnancies do not continue to birth.
• Patau syndrome (trisomy 13) An extra copy of chromosome 13. Like Edwards syndrome, it is usually very serious.Any pregnancy can be affected. These changes usually happen by chance when the egg or sperm is formed, and not because of anything the parents did. The chance does rise with the mother’s age. At age 20, the chance of Down syndrome at birth is about 1-in-1,250. At age 40, it is about 1-in-86. This is why professional guidelines, including those of the American College of Obstetricians and Gynaecologists, recommend offering screening to every pregnant person, whatever their age.
The scan part of the test can also give early clues about other conditions, such as Turner syndrome (a missing X chromosome in a girl), triploidy (a full extra set of chromosomes), and some heart and skeletal conditions.
It is important to know what first trimester screening is not. It is a screening test, not a diagnosis. It gives a chance, not a yes or no answer. It also does not check for single-gene conditions such as beta-thalassemia, sickle cell disease, or spinal muscular atrophy. Those need separate carrier screening of the parents.
First trimester screening combines three pieces of information. This is why it is often called the “combined test”. In India, the blood test part is commonly called the “double marker” test.
• The nuchal translucency scans an ultrasound scan measures a small pocket of fluid at the back of the baby’s neck, called the nuchal translucency. All babies have some fluid here. Babies with chromosome conditions tend to have more. The scan must be done when the baby measures between 45 and 84 millimetres from head to bottom, which is roughly 11 weeks to 13 weeks and 6 days. It needs a trained and certified sonologist because a difference of a fraction of a millimetre changes the result. The scan also checks the baby’s heartbeat, confirms the due date, counts the babies, and looks at early body structure.
• The blood test A sample of the mother’s blood is checked for two pregnancy hormones: free beta human chorionic gonadotropin and pregnancy-associated plasma protein A. In Down syndrome, the first is often higher than usual and the second is often lower.
• The mother’s age and details Age, weight, number of babies, and some other factors are added in.A computer program combines all three to give a single number for each condition, such as “1-in-2,500” or “1-in-150”. This means that out of 2,500 (or 150) pregnancies with the same result, 1 baby would be expected to have the condition. Each laboratory uses a cut-off, often around 1-in-250 or 1-in-300. A number with a smaller chance than the cut-off is reported as “low risk”. A number with a higher chance is reported as “high risk” or “increased chance”.
Combined screening finds about 82 to 87 of every 100 babies with Down syndrome, while flagging about 5 in every 100 pregnancies overall as high risk. A low-risk result is reassuring, but it does not rule out a chromosome condition completely.
No. A high-risk result means the chance is higher than the laboratory’s cut-off. It does not mean the baby has the condition. Because the test flags about 5 in every 100 pregnancies, and chromosome conditions are much less common than that, most pregnancies with a high-risk result turn out to have a baby with normal chromosomes. It is natural to feel frightened. The next step is to get clear answers, not to decide straight away.
• Meet a genetic counselor or clinical geneticist They will explain what your specific number means, since a result of 1-in-10 is very different from 1-in-200. They will also review the scan findings and your family history.
• Option 1: Non-Invasive Prenatal Testing This is a more accurate screening test that looks at small fragments of the baby’s DNA (from the placenta) in the mother’s blood. It carries no risk to the pregnancy. It is still a screening test, so a high-risk result from it also needs confirmation.
• Option 2: Diagnostic testing This gives a definite answer by testing the baby’s own cells. Chorionic villus sampling takes a tiny sample of the placenta, usually at 11 to 14 weeks. Amniocentesis takes a small amount of the fluid around the baby, from 15 weeks onwards. Both carry a small chance of miscarriage, which should be weighed against the chance found on screening and what the answer would mean for your family.
• What the laboratory tests for the sample is usually checked for the common trisomies, often with a rapid test. When the scan shows a thick nuchal translucency or a structural difference, guidelines recommend a chromosomal microarray. This test looks for small missing or extra pieces of chromosomes that a standard chromosome study can miss.Some families choose further testing to prepare. Others choose not to test at all. Both are valid choices, and your care team should support whichever path you take.
