chuka_lis

Полезная статья в НЙ Таймс.
Очень многие  тесты крови беременных на потенциальные генетические дефекты плода из-за микроделеций  хромосом (преимущественно, редкие явления)- обладают очень высоким показателем ложной позитивности (более 80%). При том, что оценивают вероятность дефекта как "высокую", если она выше 1%. Зачастую пациенты не осведомлены о том, что положительный результат в 8 случаях из 10 в таком тесте- ни о чем.
Интересно, как у них с ложноотрицательными результатами..
На мой взгляд, когда такая высокая ложнопозитивность -очевидн,о не хватает регуляторной функции Минздрава в этом сегменте (чтоб на рынке были более высокоспецифичные тесты).
Но нужно учитывать и немного шаткие основания- со многими единичными микроделециями есть "ассоциации", и результат (дефект развития и тд) может быть связан не только с той микроделецией, которую определяют, как показательную,  или она может не играть решающего значения в комплексе.
С генами и производными их работы- совсем не все однозначно. Слишком сложный механизм.
The tests initially looked for Down syndrome and worked very well. But as manufacturers tried to outsell each other, they began offering additional screenings for increasingly rare conditions.
The grave predictions made by those newer tests are usually wrong, an examination by The New York Times has found That includes the screening that came back positive for Ms. Geller, which looks for Prader-Willi syndrome, a condition that offers little chance of living independently as an adult. Studies have found its positive results are incorrect more than 90 percent of the time.
Nonetheless, on product brochures and test result sheets, companies describe the tests to pregnant women and their doctors as near certain. They advertise their findings as “reliable” and “highly accurate,” offering “total confidence” and “peace of mind” for patients who want to know as much as possible. Not every patient is screened for every condition; doctors decide what to order, and most companies sell microdeletion testing as an optional add-on to the Down screening. Most test makers don’t say how often their microdeletion tests are being performed. But it is clear some of the tests are in widespread use. One large test maker, Natera, said that in 2020 it performed more than 400,000 screenings for one microdeletion — the equivalent of testing roughly 10 percent of pregnant women in America. To evaluate the newer tests, The Times interviewed researchers and then combined data from multiple studies to produce the best estimates available of how well the five most common microdeletion tests perform. The analysis showed that positive results on those tests are incorrect about 85 percent of the time.

DiGeorge syndrome Affects 1 in 4,000 births Can cause heart defects and delayed language acquisition. (May appear on lab reports as “22q.”) 81% wrong
1p36 deletion 1 in 5,000 births Can cause seizures, low muscle tone and intellectual disability. 84% wrong Cri-du-chat syndrome 1 in 15,000 births Can cause difficulty walking and delayed speech development. 80% wrong
Wolf-Hirschhorn syndrome 1 in 20,000 births Can cause seizures, growth delays and intellectual disability. 86% wrong
Prader-Willi and Angelman syndromes 1 in 20,000 births Can cause seizures and an inability to control food consumption. 93% wrong
Testing companies currently offer seven microdeletion screenings. But two syndromes — Langer-Giedion and Jacobsen — are so rare that there is not enough data to understand how well the tests work. A few other tests for conditions that are not caused by microdeletions are also widely offered, with varying degrees of reliability. The screenings for Patau syndrome (which often appears on lab reports as “trisomy 13”) and Turner syndrome (“monosomy X”) also generate a large percentage of incorrect positives, while the screenings for Down syndrome (“trisomy 21”) and Edwards syndrome (“trisomy 18”) work well, according to experts. But there are hundreds of microdeletion syndromes, and the most expansive tests look for between five and seven, meaning women shouldn’t take a negative result as proof their baby doesn’t have a genetic disorder. For patients who are especially worried, obstetricians who study these screenings currently recommend other types of testing, which come with a small risk of miscarriage but are more reliable. Patients who receive a positive result are supposed to pursue follow-up testing, which often requires a drawing of amniotic fluid or a sample of placental tissue. Those tests can cost thousands of dollars, come with a small risk of miscarriage and can’t be performed until later in pregnancy — in some states, past the point where abortions are legal. After being presented with some of The Times’s reporting, half a dozen of the largest prenatal testing companies declined interview requests. They issued written statements that said patients should always review results with a doctor, and cautioned that the tests are meant not to diagnose a condition but rather to identify high-risk patients in need of additional testing. In interviews, 14 patients who got false positives said the experience was agonizing. They recalled frantically researching conditions they’d never heard of, followed by sleepless nights and days hiding their bulging bellies from friends. Eight said they never received any information about the possibility of a false positive, and five recalled that their doctor treated the test results as definitive.