A 14-year-old boy experiences severe, prolonged bleeding following a tooth extraction. He also has a history of multiple episodes of painful joint swelling following minor trauma. His parents have no bleeding problems. Evaluation shows that the patient has an inherited disorder and that one of his parents is a genetic carrier. His older sister, who does not have this condition, is pregnant. She does not know the sex of her child. She asks about the risk that her child will be affected. Which of the following is the best estimate that this child will have the disease?

Question

A 14-year-old boy experiences severe, prolonged bleeding following a tooth extraction.  He also has a history of multiple episodes of painful joint swelling following minor trauma.  His parents have no bleeding problems.  Evaluation shows that the patient has an inherited disorder and that one of his parents is a genetic carrier.  His older sister, who does not have this condition, is pregnant.  She does not know the sex of her child.  She asks about the risk that her child will be affected.  Which of the following is the best estimate that this child will have the disease?

Quizplus · Accepted Answer

11ec160b_3769_1f45_9249_dd76ae85bd37_MD0001_00 This patient is a boy with excessive bleeding and hemarthroses, suggesting a diagnosis of hemophilia A or B. Both diseases are X-linked recessive coagulation factor deficiencies. The probability that his sister will give birth to an affected child can be calculated by multiplying the following probabilities: The probability (p1) that the sister is a carrier = 0.5. The patient's father does not carry the mutation on his X chromosome because he would be affected by the disease if he did. That means the mother carries the mutation on 1 of her 2 X chromosomes. This gives the daughter a 50% chance of having inherited the mutated X chromosome and therefore being a carrier. The probability (p2) that the offspring of a female carrier will inherit the X chromosome with the hemophilia gene = 0.5. Assuming the daughter is a carrier, the probability of passing on the mutant allele is 50% as only 1 of her 2 X chromosomes is passed to her offspring. The probability (p3) that his sister will have a boy = 0.5. If the sister's child is female, the child could be a carrier of the disease but would not be affected by it. If a male child inherits the mutated X chromosome, he will have the disease. The probability that the sister will have an affected son is the probability that all 3 of the above events will take place (ie, the product of their individual probabilities): p1 x p2 x p3 = 1/2 x 1/2 x 1/2 = 1/8. Educational objective: Given phenotypically normal parents, the probability that a female sibling of a male affected by an X-linked recessive disease will give birth to an affected child is 1/8.

A 14-Year-Old Boy Experiences Severe, Prolonged Bleeding Following a Tooth