Invasive prenatal diagnosis (IPNDT) aims to detect three classes of abnormality:

(i) chromosomal abnormalities (especially trisomies, rarely monosomies and chromosomal rearrangements visible under the microscope),
(ii) sub-microscopic structural chromosome structural abnormalities (CNVs, deletions and duplications, the vast majority of which are not detected by karyotype resolution), and
(iii) diseases and syndromes caused by mutations in a single gene (monogenic diseases).

Chorionic villus sampling (CVS) and amniocentesis are performed in different biological situations and at different times.

CVS takes place from the 11th week of pregnancy. One major limitation is the fact that approximately 1% of samples show a discrepancy between placenta and amnion, due to placental mosaicism (abnormalities restricted to the placenta).

Amniocentesis, on the other hand, is possible from the 15th week of pregnancy, as soon as sufficient amniotic fluid has been formed. It will be necessary in order to confirm definitively that the foetus has been affected in the event of mosaicism.

Chromosomal abnormalities: different families of abnormality are differentiated as they exhibit shared clinical characteristics. These are common autosomal trisomies (trisomies 21, 18 and 13) which alone account for two-thirds of all abnormalities, as well as gonosomal abnormalities and rare autosomal trisomies. They can usually be identified by karyotyping. Mosaicism is a common phenomenon in gonosomal abnormalities and rare autosomal trisomies, and for this reason a confirmatory amniocentesis will be necessary. Chromosomal rearrangements visible under the microscope are extremely rare. Monosomies are not usually viable, other than monosomy X (the clinical condition known as Turner syndrome).
Sub-microscopic structural chromosome abnormalities or CNVs: these are detected using various different techniques, e.g. comparative genomic hybridisation (CGH). After ruling out chromosomal abnormalities, the main indications for performing CGH are NT ≥3.0mm or 3.5mm, one or more ultrasound anomalies (particularly of the heart and central nervous system), hydramnios and a growth abnormality.
Monogenic diseases and syndromes: if CGH has not identified an abnormality that is either pathogenic or probably pathogenic, clinical exome sequencing may be suggested in order to search for mutations responsible for monogenic diseases and syndromes (Lancet 2019:393: 747-57). Different options are available, depending on the disease, including gene panels (e.g. to find the causes of isolated or syndromic heart defects), or alternatively exhaustive testing (e.g. the 5,430 disease-associated genes known as CDGs (closest disease-causing genes) (Front. Immunol .2018; 9:1340). The indications are as follows: NT ≥3.5 mm, hydramnios, cardiac, cerebral or renal malformation, growth abnormality, cleft lips and palates, limb abnormalities (polysyndactyly, ectrodactyly), arthrogryposis, and a combination of several ultrasound signs.

Genesupport - Chromosomal abnormalities