What is the risk of Huntington's disease (HD) in a male offspring if one parent has the disease?

From the Guidelines

The risk of Huntington's disease in a male offspring if one parent has the disease is 50%. This is because Huntington's disease is an autosomal dominant genetic disorder, meaning that a person needs only one copy of the defective gene to develop the condition 1. When a parent has Huntington's disease, they have one normal copy of the gene and one copy with the HD mutation. During reproduction, each parent contributes one copy of each gene to their child, with a 50% chance of passing either the normal or mutated gene.

Key Points to Consider

• The disease is caused by an expansion of CAG repeats in the huntingtin gene on chromosome 4, which leads to the production of an abnormal protein that damages brain cells over time 1.
• Genetic counseling is recommended for families affected by Huntington's disease, and prenatal testing options are available for those planning pregnancies who wish to know the genetic status of their offspring.
• The risk applies equally to all children regardless of sex, so male and female offspring have the same probability of inheriting the condition.
• The incidence of HD is approximately 10/100,000, with an average age of onset between 35 to 45 years and symptom progression until death within 15 to 20 years of onset 1.

Clinical Implications

• Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice 1.
• Patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD in concert with initial imaging, given that imaging may be normal early on in the disease course 1.
• The Huntington Disease Society of America’s Guidelines for Genetic Testing for Huntington Disease is considered by many to be the gold standard for genetic testing for adult onset conditions 1.

From the Research

Risk of Huntington's Disease in Male Offspring

• The risk of Huntington's disease (HD) in a male offspring if one parent has the disease is related to the autosomal dominant nature of the disorder 2.
• As HD is an autosomal dominant disorder, this means that a single copy of the mutated gene is enough to cause the condition, and each child of an affected parent has a 50% chance of inheriting the mutated gene 2.
• The disease is characterized by the appearance of progressive chorea and dementia, usually in adult life, and its transmission to offspring invariably occurs before symptoms develop in the parent 2.
• Studies have shown that the utilization of prenatal and pre-implantation genetic diagnosis in HD is low, despite the availability of accurate testing methods 3.
• In the context of reproductive genetic counselling, it is recommended that both partners be offered preconceptional CAG analysis to assess the risk of passing on an expanded CAG-repeat to future offspring 4.
• This is because recent studies have shown that the expanded repeat has been observed more often in the general population than previously estimated, and the healthy partner's CAG repeat lengths in the HD gene should also be tested 4.