Topic: Huntington disease
Subject: Medicine
A 42-year-old white male is brought to your department by his wife because of the progressive loss of his mental abilities, irritability, and some irregular involuntary movements of his hands. She says that she can remember when they were newlyweds, her husbands father had a similar condition at the age of 45 and he died few years later because there was not much doctors could do for him back then. She wants to know if their children may eventually develop a similar condition in the future. None in her family has ever had this type of condition. Which of the following would be the most appropriate answer?

This patients symptoms at presentation and the family history are suggestive of Huntington disease (HD). Up to now, HD is an incurable, adult-onset, autosomal dominant inherited disorder. Characteristic features of HD include involuntary movements, dementia, and behavioral changes. The most striking neuropathology in HD occurs within the neostriatum, in which gross atrophy of the caudate nucleus and putamen is accompanied by selective neuronal loss and astrogliosis. The genetic basis of HD is the expansion of a cysteineadenosine- guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. Since it is an autosomal dominant disorder, each generation is affected and through genetic anticipation, a generation may develop the disease earlier than the previous generation. Each child has 50% risk of inheriting the disease and childs risk is independent of whether their sibling has the disorder or not.
> Only their male children are at risk (choice A) is incorrect. This occurs in X-linked recessive inherited disorders.
> If one child develops the disease, siblings are not at risk (choice B) is incorrect. In autosomal dominant disorders each child has 50% risk of inheriting the disease and a childs risk is independent of whether his/her sibling has the disorder or not.
> All their children will inherit the disease (choice C) would mean 100% risk of inheriting the disease which is incorrect. Each child has 50% risk of inheriting the disease.
> Each child has 25% risk of inheriting the disease (choice E) would be consistent with an autosomal recessive inheritance pattern (where both parents are carriers); HD is an autosomal dominant inherited disease.
Key point:
Huntington disease is an autosomal dominant inherited disorder that presents with involuntary movements, dementia, and behavioral changes. Each generation is affected and each child has 50% risk of inheriting the disease. acteristic features of HD include involuntary movements, dementia, and behavioral changes. The most striking neuropathology in HD occurs within the neostriatum, in which gross atrophy of the caudate nucleus and putamen is accompanied by selective neuronal loss and astrogliosis. The genetic basis of HD is the expansion of a cysteineadenosine- guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. Since it is an autosomal dominant disorder, each generation is affected and through genetic anticipation, a generation may develop the disease earlier than the previous generation. Each child has 50% risk of inheriting the disease and childs risk is independent of whether their sibling has the disorder or not.
> Only their male children are at risk (choice A) is incorrect. This occurs in X-linked recessive inherited disorders.
> If one child develops the disease, siblings are not at risk (choice B) is incorrect. In autosomal dominant disorders each child has 50% risk of inheriting the disease and a childs risk is independent of whether his/her sibling has the disorder or not.
> All their children will inherit the disease (choice C) would mean 100% risk of inheriting the disease which is incorrect. Each child has 50% risk of inheriting the disease.
> Each child has 25% risk of inheriting the disease (choice E) would be consistent with an autosomal recessive inheritance pattern (where both parents are carriers); HD is an autosomal dominant inherited disease.
Key point:
Huntington disease is an autosomal dominant inherited disorder that presents with involuntary movements, dementia, and behavioral changes. Each generation is affected and each child has 50% risk of inheriting the disease. h generation is affected and each child has 50% risk of inheriting the disease.
child has 25% risk of inheriting the disease (choice E) would be consistent with an autosomal recessive inheritance pattern (where both parents are carriers); HD is an autosomal dominant inherited disease.
Key point:
Huntington disease is an autosomal dominant inherited disorder that presents with involuntary movements, dementia, and behavioral changes. Each generation is affected and each child has 50% risk of inheriting the disease. .