What is the best initial statement to a 32-year-old primigravid (first pregnancy) woman at 18 weeks gestation with a detected pathogenic variant for the HEXA (hexosaminidase A) gene, consistent with Tay-Sachs disease, given her family history?

From the Guidelines

The patient should be informed that she is a carrier of Tay-Sachs disease, but this does not necessarily mean her baby will be affected, and the next step is to recommend genetic testing for the baby's father to determine if he is also a carrier. Since Tay-Sachs is an autosomal recessive condition, the baby would need to inherit pathogenic variants from both parents to develop the disease 1. The patient's carrier status is based on the detection of a pathogenic variant for the HEXA gene, which is consistent with Tay-Sachs disease.

Key Points to Discuss with the Patient

• The patient is a carrier of Tay-Sachs disease, which means she has a pathogenic variant of the HEXA gene, but she will not develop the disease herself 1.
• The baby's father should undergo genetic testing to determine if he is also a carrier of the disease.
• If the father is not a carrier, the baby will at most be a carrier like the mother, but will not develop Tay-Sachs disease.
• If the father is also a carrier, there is a 25% chance that the baby could inherit pathogenic variants from both parents and develop the disease.
• Further prenatal diagnostic testing, such as amniocentesis or chorionic villus sampling, could be offered to determine if the fetus has inherited both pathogenic variants if the father is found to be a carrier 1.

Importance of Genetic Counseling

Genetic counseling should be readily available to discuss the findings and possible reproductive options with the patient and her partner 1. It is essential to inform them about the importance of genetic counseling for other family members and encourage them to discuss the findings with their family if possible and appropriate.

Testing for the Baby's Father

The baby's father should be tested for Tay-Sachs disease using a biochemical assay, which has an excellent detection rate regardless of ethnic or racial background 1. This will help determine the risk of the baby developing the disease and guide further management and decision-making.

From the Research

Initial Statement to the Patient

The best initial statement to the patient would be to explain the results of the genetic testing and the implications for the fetus.

• The patient has been found to be a carrier of a pathogenic variant for the HEXA gene, which is associated with Tay-Sachs disease 2.
• The patient's cousin's child died from Tay-Sachs disease, which suggests a family history of the condition.
• The patient is currently 18 weeks pregnant with a male fetus, and the genetic testing results indicate that the fetus may be at risk of inheriting the condition.

Risk Assessment and Counseling

• The patient should be counseled about the risks and implications of being a carrier of the HEXA gene variant, including the 25% risk of having an affected child with each pregnancy if the other parent is also a carrier 3.
• The patient should be informed about the options available for prenatal diagnosis, including amniocentesis or chorionic villus sampling, and the benefits and risks of each procedure 4, 5.
• The patient should also be counseled about the possibility of egg or sperm donation, preimplantation diagnosis, or adoption as alternatives to prenatal diagnosis 3.

Next Steps

• The patient's partner should be tested to determine if they are also a carrier of the HEXA gene variant.
• If the partner is found to be a carrier, the couple should be counseled about the risks and implications of having an affected child and the options available for prenatal diagnosis and reproductive planning.
• The patient should be referred to a genetic counselor for further counseling and support.