A 22-year-old woman comes to the physician at 8 weeks gestation for routine prenatal counseling. Her husband has hemophilia A. Her own family history is insignificant. She is concerned about the possibility of her child having hemophilia. Which of the following is the best response to her questions?

Question

A 22-year-old woman comes to the physician at 8 weeks gestation for routine prenatal counseling.  Her husband has hemophilia A.  Her own family history is insignificant.  She is concerned about the possibility of her child having hemophilia.  Which of the following is the best response to her questions?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c161_43cd_8f63_81faadac067a_MD0005_00 Hemophilia A is an inherited bleeding disorder that is due to a deficit in coagulation factor VIII. It is an X-linked recessive disease that affects mainly males; heterozygous females are silent carriers. This patient is not affected, and it is very unlikely that she is a carrier for the disease as she has no specific family history. The father is affected by the disease, but can transmit the affected X chromosome only to his female children. Therefore: If the child is female, she will receive her father's hemophilia X chromosome and a healthy X chromosome from her mother; she will be a silent carrier of the disease. If the child is male, he will receive his father's Y chromosome and a healthy X chromosome from his mother; he will be unaffected by the disease. Thus, neither a male nor female child will likely be affected by the disease, but there are rare exceptions to this general prediction. A female child could be affected if the mother was a silent carrier for hemophilia A or if she has impaired gene expression of her normal X- chromosome (eg, 45,X karyotype or X mosaicism) (Choice A). Likewise, a male child could be affected if the mother were a silent carrier despite her negative family history. All of these scenarios are very uncommon, though they raise the risk slightly over that in the general population. (Choice B) The probability of a child having a genetic disease is 25% for autosomal recessive disorders when both parents are silent carriers. It is also 25% for X-linked disorders when the mother is a carrier (50% of males are affected + 0% of females). (Choice C) The probability of a child having a genetic disease is 50% for autosomal dominant disorders when one parent is affected. It is also 50% for male children when the mother is a carrier of an X-linked disorder. (Choice E) Hemophilia A is a monogenetic (not polygenetic) disease. Educational objective: If the father is affected by an X-linked recessive disease and the mother is not a carrier, their children will not be affected by the disease, although all their female children will be carriers. References: Hemophilia: a practical approach to genetic testing. (http://www.ncbi.nlm.nih.gov/pubmed/16295028) Genetics and epigenetics of the X chromosome. (http://www.ncbi.nlm.nih.gov/pubmed/21382199)

A 22-Year-Old Woman Comes to the Physician at 8 Weeks