X_linked_Recessive_Flashcards
What is X-linked recessive inheritance?
In X-linked recessive inheritance, only males are typically affected. The disorders are transmitted by heterozygous female carriers, and there is no male-to-male transmission.
What is an exception to typical X-linked recessive inheritance?
An exception is seen in patients with Turner’s syndrome, who are affected due to having only one X chromosome.
What is the risk of inheritance for children of a heterozygous female carrier?
Each male child of a heterozygous female carrier has a 50% chance of being affected, while each female child has a 50% chance of being a carrier.
Can affected males have affected sons?
Affected males can only have unaffected sons and carrier daughters, as they cannot pass the affected X chromosome to their sons.
How common is it for an affected father to have children with a heterozygous female carrier?
This scenario is generally extremely rare. However, in certain Afro-Caribbean communities, G6PD deficiency is relatively common, and homozygous females with clinical manifestations of the enzyme defect are seen.
summarise
X-linked recessive
In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner’s syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters.
Each male child of a heterozygous female carrier has a 50% chance of being affected whilst each female child of a heterozygous female carrier has a 50% chance of being a carrier.
The possibility of an affected father having children with a heterozygous female carrier is generally speaking extremely rare. However, in certain Afro-Caribbean communities G6PD deficiency is relatively common and homozygous females with clinical manifestations of the enzyme defect are seen.
A 10-year-old boy is found to have haemophilia A following investigation for a haemoarthrosis. Which one of his relatives is most likely to have the condition?
Father
Mother’s brother
Father’s sister
Mother
Father’s brother
Mother’s brother
X-linked recessive conditions are only seen in males which therefore excludes two of the options. As male to male transmission is not seen this means the answer is mother’s brother.
Which of the following statements is true regarding X-linked recessive inheritance?
A female child of a heterozygous female carrier has a 50% chance of being a carrier
An example is Friedreich’s ataxia
50% of the male offspring of affected males will manifest the disease
An affected child’s uncle on the paternal side will also manifest the disease
50% of the female offspring of affected males will be carriers
A female child of a heterozygous female carrier has a 50% chance of being a carrier
The correct answer is A female child of a heterozygous female carrier has a 50% chance of being a carrier. This is true because in X-linked recessive inheritance, females have two X chromosomes and thus can be carriers without showing the disease phenotype. If a female is heterozygous for an X-linked recessive trait, she will pass on the affected X chromosome to approximately half of her offspring. Therefore, each female child has a 50% probability of inheriting the affected gene and thus being a carrier.
An example is Friedreich’s ataxia is incorrect. Friedreich’s ataxia is an example of autosomal recessive inheritance, not X-linked recessive inheritance. It means that this disorder affects both sexes equally and requires two copies of the mutated gene, one from each parent, to manifest the disease.
50% of the male offspring of affected males will manifest the disease is also incorrect. In fact, none of the male offspring from an affected male will inherit the disease because males pass on their Y chromosome to their sons, not their X chromosome which carries the mutation.
The statement An affected child’s uncle on the paternal side will also manifest the disease is false as well. In X-linked recessive inheritance diseases, an affected male cannot pass on his condition to his nephews through his brothers since he passes his Y chromosome to his sons who are their fathers.
Lastly, 50% of the female offspring of affected males will be carriers is wrong because all female offspring (100%) from an affected father would be carriers. This occurs because daughters always receive their father’s single X chromosome which carries the mutation in case he suffers from an X-linked recessive disorder.
A 14-year-old girl presents with a swollen left knee. Her parents state she suffers from haemophilia and has been treated for a right-sided haemarthrosis previously. What other condition is she most likely to have?
Turner’s syndrome
Down’s syndrome
Ataxia telangiectasia
Hunter’s syndrome
Coeliac disease
Haemophilia is a X-linked recessive disorder and would hence be expected only to occur in males. As patients with Turner’s syndrome only have one X chromosome however, they may develop X-linked recessive conditions
You are speaking to a 24-year-old man who is known to have haemophilia A. His wife has had genetic testing and was found not to be a carrier of haemophilia. He asks you what the chances are of his future children developing haemophilia. What is the correct answer?
0%
25%
50%
50% if male, 0% if female
100%
X-linked recessive conditions - there is no male-to-male transmission. Affected males can only have unaffected sons and carrier daughters.
Important for meLess important
As we now know that mother is not a carrier of the disease there is no chance that any future children could develop haemophilia. You should of course also discuss with him that any daughters that he has will be carriers of the condition.
A 35-year-old man, known to suffer from haemophilia A (factor VIII deficiency), presents to the GP surgery. His wife is currently 28 weeks pregnant with their first son and has no family history of clotting disorders. The patient is concerned that the new baby could inherit haemophilia A.
What is the percentage chance that the patient’s son will be affected?
0%
25%
50%
100%
Impossible to calculate
0%
X-linked recessive conditions - there is no male-to-male transmission. Affected males can only have unaffected sons and carrier daughters.
Important for meLess important
0% is the correct answer. Haemophilia A is an X-linked recessive condition. As the child is male, he will inherit an X chromosome from his mother and a Y chromosome from his father. As he can’t inherit one of his father’s haemophilia-affected X chromosomes, he cannot be affected. By contrast, any female children will be carriers, as they will inherit a haemophilia-affected X chromosome from their father and a normal one from their mother.
25% - If a carrier daughter of this patient has a child with an unaffected male, there is a 25% chance that her child will be affected. Only male children would be at risk, so if she found out the child was male then the chance rises to 50%.
50% - if the child is a girl and it turns out her mother is a carrier, there is a 50% chance that this child would be affected by the condition. She will have one haemophilia-affected X chromosome from her father, but she may or may not inherit her mother’s.
100% - if the haemophiliac patient were the mother, a male child has a 100% chance of being affected as both his mother’s X chromosomes carry the haemophilia A gene. He must inherit one of them, and a Y chromosome from his father.
Impossible to calculate - this answer is incorrect as haemophilia is known to have an X-linked recessive inheritance pattern. However, some female carriers can exhibit symptoms due to X-inactivation.
A couple attend the GP practice seeking advice as they are currently pregnant with their first son. The father suffers from haemophilia A and is worried about the risk of passing this disease onto his son. The mother is not a carrier and has no family history of any disorders. What is the percentage chance of the baby inheriting haemophilia A?
0%
25%
50%
75%
100%
0%
There is no male-to-male transmission in X-linked recessive conditions
X-linked recessive conditions are only passed on from mothers (carriers) to sons. In this case, the father can only pass on the gene to his daughters who will become carriers and he cannot pass on the gene to his sons as they inherit the Y-chromosome from him.
