Down Syndrome: Screening and Pregnancy Test

Clinical phenotype

To learn more: Symptoms of Down Syndrome

The genetic anomaly that accompanies Down syndrome determines the characteristics of the syndrome, both directly and by influencing the functioning of genes located on other chromosomes. As a result, there is great individual variability in phenotypic and clinical manifestations. In addition to genetic factors, many of the differences depend on the type of education received in the family, at school and in general in the environment surrounding these people.

Patients with Down Syndrome have different psycho-physical abnormalities of varying degrees (mild, medium or severe), with mental retardation and a higher incidence of some systemic diseases.

PECULIAR PHYSICAL CHARACTERISTICS: there are numerous phenotypic peculiarities characterizing subjects with Down syndrome; despite a certain individual variability, among the most common anomalies we note: small skull with flattening at occipital level, roundish face with flattened profile, small and round ears with low insertion, short nose with flat root, palpebral rhymes with trend (oblique from above below and from outside to inside), small mouth, small and irregular teeth, voluminous tongue crossed by deep fissures, palms crossed by a single transverse groove, short fingers with clinodactyly of the fifth finger, muscular hypotonia at birth and laxity ligament.

SYSTEMIC DISEASES: in people with Down syndrome there is an increased incidence of cardiological diseases (congenital heart disease), malformations of the digestive tract, leukemia, alopecia, growth retardation in adulthood below the tenth percentile, overweight / obesity, eye diseases (myopia, cataract, strabismus), problems of the immune system (greater susceptibility to infections, especially of the respiratory tract), hypothyroidism, otoiatric diseases (recurrent catarrhal otitis) and orthopedic diseases (flat foot, valgus knee) due to the already mentioned ligamentous laxity.

PSYCHIC ASPECTS: mental retardation is constantly present, varying in degree between the medium and the mild, with a tendency to aggravation with age. Patients with Down syndrome develop neuropathological signs of Alzheimer's disease at a much earlier age than normal individuals

The life expectancy of people with Down syndrome has improved considerably over the past 50 years; according to the most recent data, in economically advanced countries it is about half a century, compared with 16 years in the early 1950s and 10 years in 1929.

Screening tests during pregnancy

The first screening method for trisomy 21, introduced in the early 1970s, was based on the association with maternal age. In fact, the risk of having a child with Down syndrome increases with increasing maternal age, according to the trend illustrated in the figure (below). Thus, between the ages of twenty and thirty, the increase in risk is rather modest, while it becomes relevant after thirty-five years.

Below, we report a simple calculation form to quantify the theoretical risk of giving birth to a child with Down syndrome, in relation to maternal age.

The relationship between maternal age and prevalence of Down syndrome at birth was almost comparable in different parts of the world.

Of course, science now has many tools available to better characterize this risk. The so-called "triple test", for example, is based on the assay of three serum markers: alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol.

The joint analysis of the results of these tests can identify 50 to 80% of trisomy 21 cases, while the risk of false positives is around 5%. To further improve these percentages, an additional serum marker, called inhibin A, can be evaluated (in this case we no longer speak of triple tests but of quad tests).

The risk of carrying a child with Down syndrome in the womb is considered high when the mother has high blood levels of inhibin A and human chorionic gonadotropin, associated with a reduction in those of estriol and alpha-fetoprotein.

The examinations listed so far are carried out during the second trimester of pregnancy, generally between the fifteenth and twentieth week of gestation; even earlier tests carried out towards the end of the first trimester (week 11 - 13) include the dosage of the plasma protein A associated with pregnancy (PAPP-A) and of the free fraction of the β subunit of hCG (free-βhCG), together with the ultrasound examination of nuchal translucency.

Before the affirmation of the so-called triple test, the prenatal diagnosis of Down syndrome was entrusted to an examination still in vogue, but not without risks. We are talking about amniocentesis, a technique based on taking a sample of amniotic fluid using a thin needle inserted into the uterus through the abdomen. The risk of abortion caused by amniocentesis is around 0.06% - 0.5% and increases with decreasing gestational age; for this reason it is generally performed after the 15th week of gestation, naturally under the guidance of an ultrasound probe.

Other invasive tests used for the early diagnosis of Down syndrome are chorionic villus sampling (villocentesis), performed between the 9th and 14th week of gestation (risk of abortion 1%) and the taking of an umbilical blood sample by way of percutaneous (risk of abortion superior to other methods). Amniocentesis and chorionic villus sampling are generally performed in cases where the triple or quad test show a great risk of carrying fetuses with Down syndrome in the womb; despite the significant risk of abortion, in fact, these two examinations have a diagnostic accuracy close to 99%. This means that the use of these tests is on average able to identify 98 to 99 actual Down syndrome cases out of 100.

For further information: nuchal translucency, PAPP-A, tri-test, combined test in pregnancy.

Care and treatment

To learn more: Drugs to treat Down Syndrome

The adoption of a strategy of early enabling intervention is fundamental to fully exploit the psycho-physical development potential of children with Down syndrome. Therefore the contribution of the various associations present in the territory is of great help, which cannot however disregard a deep involvement of the family members. Down children can learn - albeit to an extent that depends on the severity of their symptoms - to carry out the activities normally performed by other children, such as playing, talking, building, playing sports, even if this requires longer learning times.