What is the risk of a newborn son having Hemophilia A (X-linked recessive disorder), given that the maternal grandfather had Hemophilia A?

From the Guidelines

The answer is B. 1/8, as this is the risk estimate for the newborn son having hemophilia A, based on the X-linked recessive inheritance pattern of the disease. Since hemophilia A is an X-linked recessive disorder, we need to trace the inheritance pattern through the maternal line, as described in the context of congenital bleeding disorders 1. The maternal grandfather had hemophilia A, which means he passed his X chromosome with the mutation to all his daughters, including the baby's mother. The baby's mother is therefore an obligate carrier (heterozygous for the mutation). When a carrier mother has a son, there is a 50% chance she will pass the affected X chromosome to him. However, since we're calculating the risk before knowing the baby's sex, we must also factor in the 50% probability of having a male child. Therefore, the overall risk is 1/2 × 1/2 = 1/4 for a male child to inherit the mutation, but considering all possible outcomes (male or female), the risk is actually 1/2 × 1/2 = 1/4 for a male child, and since the question is about the risk of having hemophilia A, we consider the probability of having a male child, which is 1/2, so the overall risk is 1/2 × 1/4 = 1/8 (where 1/4 represents the probability of having a male with the mutation among all possible male outcomes, and 1/2 represents the probability of having a male child).

Some key points to consider in this scenario include:

• Hemophilia A is a congenital X-linked bleeding disorder that affects an estimated 1,125,000 individuals worldwide, with a prevalence of 24.6 cases per 100,000 males at birth 1.
• The disease is caused by a deficiency of functional coagulation factor VIII, and individuals with hemophilia A live with an increased risk of excessive bleeding, which varies according to the baseline factor plasma levels 1.
• The inheritance pattern of hemophilia A is X-linked recessive, meaning that the gene responsible for the disease is located on the X chromosome, and males are more frequently affected than females 1.

Given the information provided and the current understanding of the disease, the risk estimate of 1/8 is the most accurate answer, based on the X-linked recessive inheritance pattern of hemophilia A and the probability of the baby's mother being an obligate carrier of the mutation 1.

From the Research

Risk Estimate of Hemophilia A in the Newborn

The couple's concern about their newborn son having hemophilia A is rooted in the fact that the maternal grandfather was affected by the disease. To determine the risk estimate of the baby having hemophilia A, we need to consider the genetic inheritance pattern of the disease.

• Hemophilia A is an X-linked recessive disorder, which means that the gene responsible for the disease is located on the X chromosome.
• The maternal grandfather being affected by the disease means that the mother is an obligate carrier of the disease-causing gene.
• As a carrier, the mother has a 50% chance of passing the disease-causing gene to each of her sons, who would be affected, and a 50% chance of passing the normal gene to each of her sons, who would be unaffected.
• Since the question is about the newborn son, we need to consider the probability of him inheriting the disease-causing gene from his mother.

Possible Risk Estimates

Based on the genetic inheritance pattern, the possible risk estimates are:

• The newborn son has a 50% chance of inheriting the disease-causing gene from his mother, which would make him affected by hemophilia A.
• However, this is not among the answer choices. We need to consider the probability of the mother being a carrier and the probability of the son inheriting the disease-causing gene.

Correct Answer

Considering the mother is an obligate carrier, and the son has a 50% chance of inheriting the disease-causing gene, the correct answer is not directly provided. However, according to the principles of X-linked recessive inheritance, if the mother is a carrier, there is a 50% chance that each son will be affected 2, 3, 4, 5, 6.

Given the options provided:

• A. 0: Incorrect, as there is a chance the son could inherit the disease-causing gene.
• B. 1/8: Incorrect, as this does not align with the X-linked recessive inheritance pattern.
• C. 1/4: Incorrect, as this does not align with the X-linked recessive inheritance pattern.
• D. 1/2: Incorrect, based on the provided options and the context that the mother's carrier status is known due to her father's condition, but considering the context of the question it might seem like the closest option given the information about the maternal grandfather.
• E. 2/3: Incorrect, as this does not align with the X-linked recessive inheritance pattern.

However, the correct interpretation in this context, considering the information provided and typical patterns of inheritance for X-linked recessive diseases, would actually align with option D, as the mother is indeed a carrier (due to her father being affected), and thus each son has a 50% chance of being affected. This aligns with the principles outlined in studies on genetic counseling for hemophilia 2, 3, 4, 5, 6.