Counselling for couples with genetic abnormalities and inheritable conditions

Detection of genetic abnormalities in the antenatal period can significantly affect the outcome of a pregnancy. Congenital ab­normalities as a cause of death in the perinatal period have de­creased dramatically from 1960 to 2013 (101, 102).

1. 7, and 2.8 per 1000 live births in 1959-1961 in England and Wales (102), respectively, to 1.1, 0.4, and 1.2 per 1000 live births in 2013 (101). This can be attributed, in part, to the higher rates of detection in the prenatal period, with medical advances in treatment options as well as subsequent selective termination.

New advances in genetic screening tests have made preconceptional carrier testing possible through genetic testing across single genes and more recently multiple genetic mutations with genome sequencing. Typically, carrier testing is performed on the maternal genes, followed by paternal testing if any genes of interest are identified. This can be offered to couples at high risk for specific inheritance, or for those who wish to pursue this testing through the private sector. Additionally, advancements in tests available during the conceptional period include non- invasive prenatal testing (NIPT), whereby cell-free fetal DNA can be measured with very precise relative quantification in the ma­ternal circulating blood, and used for early diagnosis of genetic conditions in the first trimester. Although this is not the standard method of screening for chromosomal abnormalities, non- invasive testing is being used more commonly as a screening tool to diagnose several genetic conditions due to the high sensitivity and specificity that it offers.

During a preconceptional evaluation of couples with genetic ab­normalities, specific factors should be discussed in detail, including personal and family history of known or suspected inheritable dis­eases, consanguinity, advanced maternal and paternal age, potential teratogen exposure, ethnic background with an increased preva­lence of disease, and recurrent pregnancy loss. If any of these factors are of concern, genetic counselling referral with a geneticist is indi­cated and should be done preconceptionally if possible.

When an inheritable disease is identified, a couple should be in­formed regarding the likelihood of future offspring developing the condition, which may depend on the pattern of inheritance, in­cluding Mendelian versus di- or multigenic, as well as penetrance and variable expression. The burden of disease on both the inheriting individual as well as the family should be discussed, including the potential for requirement for chronic hospitalization or shortening of life span; cost of treatments; impact on future reproductive po­tential; and effects on physical and mental development, with special consideration of future ability to engage in activities of daily living independently.

In planning conception, it is important to discuss the expect­ations of a couple, including the types and sensitivity of genetic tests available, including amniocentesis, chorionic villus sampling, NIPT, and ultrasonography, and if the couple would wish to pursue investigations. Alternative options to modify the impact of dis­ease for couples with known inheritable disease include artificial insemination by donor, ovum transfer from surrogate, as well as adoption.