What happens during a genetic consultation?
During a genetic consult, the genetic expert understands the different symptoms and takes a three-generation family history asking questions which are pertaining to clinical manifestations. Based on this information and further discussion with the referring clinician, a genetic test is recommended. The family is then counseled about the diagnosis, prognosis, and also available options of management or in few cases variable options for treatment. The genetic diagnosis helps the genetic expert to also confirm the provisional diagnosis made by clinicians and predict recurrence risk in the next generation. This discussion involves understanding the social, economic background of the family and understand the concerns and help them in making informed choices.
Can you break down the evaluation and testing process for genetic diagnosis of unknown Genetic disorder Vs a Know Genetic disorder
A clinician refers a family based on certain concerns. Genetic testing is not a one test fit all kind of a test. Also, the analysis is a bit complicated. Hence detailed information is needed and a pretest counseling is done to the family so that they understand why this was recommended and what test are they doing and what are the outcome and possible expectations from the report.
Once done the genetic expert along with the clinician would suggest the tests depending on clinical manifestations, age of onset, family history, the inheritance pattern, the etiology, population incidence the other parameters. Once the report arrives it might be relevant or might be likely relevant or might not be useful. To establish this there can be further family studies that might be needed especially in case of an unknown variant identified. At times further biochemical or radiological tests can also be done in view of the genotype identified to correlate or establish the finding. Based on the genotype identified through the genetic test and the clinical correlation, a diagnosis can be established.
In the case of a known genetic disorder targeted testing for that particular disorder or that group of disorders can be done.
Why is Family history necessary? What if there is no way of providing such information?
Family history is needed to understand the inheritance pattern of the disease which gives a clue to the genetic etiology. In cases where no family history is available; say… if the child is adopted etc, in such cases we have to depend only on clinical indications and biochemical and radiological evaluations in order to understand the disorder.
How can Genetic counseling help for couples with recurrent pregnancy loss but have no family history of Genetic disorder?
Recurrent pregnancy loss can be due to multiple reasons. It can be due to anatomical reasons, infectious reasons, endocrinological reasons, immunological reasons, thrombophilia, chromosomal or genetic reasons. When a couple is referred, a genetic expert would look into each of these aspects. Family history and targeted questioning would help to understand additional information like the presence or absence of PCOD, or the possibility of genetic disorders like myotonic dystrophy or the possibility of recessive gene disorder than render the fetus lethal.
Also, the genetic expert would study and understand the possibility of chromosomal problems. Couples can be carriers of balanced translocation which can cause chromosomal aneuploidy in the embryos. There is also some form of hereditary thrombophilia like the HRG gene which is not picked up in regular thrombophilia workup. So a genetic expert will help to unravel these aspects of recurrent pregnancy loss. And help them plan a pregnancy in a more informed way through proper management options.
How is the recurrence risk of a genetic disorder calculated?
Recurrence risk is calculated on the basis of the inheritance pattern, penetration of the gene, and population prevalence.
Is there a definitive way of knowing if the developing fetus is carrying the genes for a couple with known genetic factors in the family?
If there is an established diagnosis in the index child or the index family member then there is a definitive way to know the status of the Fetus through prenatal diagnosis. Couples would then be referred for invasive fetal diagnosis procedures like Amniocentesis / Chorionic villi sampling to get a sample of Fetal DNA which would undergo further DNA analysis to see if it carries the know genetic mutation.
What are the common disorders that can be screened by prenatal screening?
Chromosomal aneuploidies, thalassemia, etc. are routinely screened. If there is any established genetic diagnosis that can also be investigated.
How many genetic disorders are out there that fall under the panel of genetic testing?
There are many kinds of genetic disorders. What we can test is basically the single-gene disorders which consist of about 7000 diseases. It is important to remember that Genetic testing is not one test fit all. So even if there are disease type aggregates and panels, genetic testing is always based on the clinical manifestations and family history.
In the case of an asymptomatic carrier screening couple, they are screened based on the population incidence of genetic disorders - few disorders are more common in a few families. Normally for carrier screening autosomal recessive Gene like an inborn error of metabolism, various storage disorders, bone disorders, blood disorders, neuromuscular, neuromotor, cardiomyopathy, etc., related Genes are screened which means those Genes that cause disease when two mutant copies are present.
What would be your step by step approach for a couple whose prenatal screening indicated a higher risk of a certain genetic disorder?
Explain the diagnosis, prognosis, set their expectation to what they will experience, discuss about the quality of life for the fetus, management/treatment of the disease-related questions, implications of the disease in the life of the fetus, whether this is pro-life or has a poor outcome. Couples are also often referred to a patient support group if indicated to talk about day-to-day concerns and understand the disease prognosis from their point of view. Couples also are counseled about recurrence risk if indicated. Discuss about planning the next pregnancy and management options available.