A 32-year-old primigravid woman comes to the clinic for a routine prenatal visit and anatomy ultrasound. The patient has no chronic medical conditions and is at 18 weeks gestation. The patient would like to undergo genetic testing because she had a cousin whose child died from Tay-Sachs disease a few years ago. Examination is unremarkable, and ultrasound confirms a male fetus at 18 weeks gestation. Genetic testing in the woman detects a pathogenic variant for the HEXA gene, consistent with Tay-Sachs disease. Which of the following is the best initial statement to the patient?

Question

A 32-year-old primigravid woman comes to the clinic for a routine prenatal visit and anatomy ultrasound.  The patient has no chronic medical conditions and is at 18 weeks gestation.  The patient would like to undergo genetic testing because she had a cousin whose child died from Tay-Sachs disease a few years ago.  Examination is unremarkable, and ultrasound confirms a male fetus at 18 weeks gestation.  Genetic testing in the woman detects a pathogenic variant for the HEXA gene, consistent with Tay-Sachs disease.  Which of the following is the best initial statement to the patient?

Quizplus · Accepted Answer

11ec25c8_da89_230b_bc81_6907f7de6b71_MD0003_00 Prenatal screening for a variety of diseases is a common component of routine prenatal care that is offered to all patients for reproductive planning. The screening approach is often based on the disease prevalence, how detrimental the disease is to quality of life, and if there are available interventions to treat or improve the disease course. Tay-Sachs disease is a condition in which carrier screening is often performed because it is an autosomal recessive disease (caused by a hexosaminidase A [HEXA] enzyme deficiency) that results in progressive neurodegeneration and early childhood death. For a child to inherit an autosomal recessive condition, such as Tay-Sachs disease, each parent must contribute one abnormal gene allele. In mothers who test positive for a pathogenic variant in an autosomal recessive condition, there is a 50% chance that her abnormal allele will be passed on to her child. However, in contrast to autosomal dominant diseases, this does not guarantee that the child will be affected (Choices C and D). Therefore, the best next step is to evaluate the father for the pathogenic variant. If the father has no abnormal variants, the child has no chance of inheriting the disease. In contrast, if the father is a carrier of an abnormal allele, the child has a 50% chance of being a carrier (ie, one abnormal allele), a 25% chance of having no abnormal alleles, and a 25% chance of inheriting the disease. autosomal recessive If both parents have pathogenic variants, then invasive testing with chorionic villus sampling or amniocentesis for fetal DNA sequencing can provide a definite diagnosis of whether or not the child will be affected by the disease (ie, 2 abnormal gene alleles) (Choice A). chorionic villus sampling amniocentesis (Choice B) Tay-Sachs disease screening is performed either through DNA sequencing or biochemical analysis with measurement of HEXA enzyme activity. Because this mother already had screening with DNA sequencing, it is not necessary to repeat the screening process with enzyme activity levels. Educational objective: Carrier screening is offered to all patients based on carrier frequencies and family history to allow for reproductive planning. Autosomal recessive disorders (eg, Tay-Sachs) require abnormal gene variants in both parents for the child to inherit the disease. Testing the father is the next best step to determine the child's inheritance risk.

A 32-Year-Old Primigravid Woman Comes to the Clinic for a Routine