An unaffected person always gives normal copies of the gene to the next generation. In contrast, an HD affected person can pass on either a normal or an abnormal copy of the gene in a 50:50 probability (provided that he/she is heterozygous for the HD gene). Hence, when one parent carries the HD gene, the children will inherit a normal gene from the unaffected parent and will have a 50% risk of inheriting the abnormal gene from the affected parent.
No, this is impossible. You must be born with the abnormal HD gene in order to develop the disease.
Not necessarily. The risk of being affected is 50% for each child of a person who carries the HD gene.
The overall risk of inheriting the HD gene is always 50% for each child (provided that only one parent is affected and carries only one abnormal copy of the gene). This does not mean that half of the children in any family will inherit the HD gene. For example, in a family of three children, it is possible for one, two or all three children to inherit the abnormal gene or for all three children to only inherit the normal gene.
This is a mere coincidence. HD may affect both men and women equally.
It means that either your mother, your father or one of your grandparents carries the HD gene, regardless of whether he/she has already developed the symptoms or not. If one of your parents is affected, your risk of inheriting the HD gene is 50%. If a grandparent is affected and it is not known whether your parent carries the HD gene, then your risk of inheritance is statistically 25%.
By definition a carrier is not affected by the disease, unless he/she begins to show symptoms and signs.
People who inherit the abnormal HD gene may develop the disease, depending on the number of the CAG repeats, although usually not before mid-adult life. They may pass the mutant gene on to their children. However, as explained above, their children have 50% chance of inheriting either the abnormal or normal copy of the gene.
Every child of a parent who carries the HD gene has a 50% risk of inheriting the abnormal gene. If you carry a risk of 50% yourself and have decided not to undergo genetic testing, statistically your child will have a risk of 25%.
If a person does not inherit the HD gene, he/she will not develop the disease and will not pass HD on to the next generation. The HD gene cannot skip a generation, but the symptoms can. This situation may occur if the gene carrier dies before the symptoms appear, so that it becomes more difficult to establish a family history.
Yes, the risk of inheriting the HD gene is 50% at your birth time. After you pass mid-adult life, the likelihood of developing HD decreases as you get older. If you reach 60 years of age without any symptoms, your risk of developing HD will be lower.
Some families have an older average age at disease onset than others. The determinants of age at disease onset are complex and currently under investigation. There is an indirect correlation between the trinucleotide repeat length and the age at onset. This means that, in general, the higher the number of CAG repeats, the earlier the onset of symptoms. However, the CAG repeat number is not the only factor that affects age of onset. This relation seems to be influenced by other genes (called genetic modifiers). Environmental factors may also play a role.
In general, HD symptoms show up when the trinucleotide repeat has more than 40 CAG units. Individuals with an intermediate CAG repeat length (36–39 CAG repeats) may be affected very late in life or may never show any symptoms at all. On the other hand, larger CAG expansions are typically associated with an early disease onset (under 20 years of age) as seen in juvenile HD cases. There is a wide range of repeat sizes, but patients with disease onset under 10 years (infantile HD) often have more than 80 CAG repeats.
In 75% of juvenile HD cases the mutation is inherited from the father and in 25% of cases from the mother. When the gene has more than 29 CAG units, the number of repeats may increase as the gene is passed on to the next generation, but this is very rare. When the gene has the number of CAG units that causes disease (36 and more) the repeat is more likely to change size when passed from one generation to the next. When the CAG repeat is inherited from the father, it is more likely to increase than decrease. The successive increase in the number of repeats leads to an earlier onset of symptoms, a phenomenon known as anticipation. As this is more likely to occur if the HD affected parent is the father, most cases of juvenile HD are inherited from the father.
Juvenile onset is rare. If a man is affected, it does not follow that his children will necessarily have juvenile HD.
Yes, but this is very rare. “De-novo” HD mutation refers to the situation where HD appears in a family without a history of the disease. This means that a new, spontaneous mutation occurred which was not inherited from either parent. In particular cases when the number of trinucleotide repeats shows borderline values (i.e. 35−39 repeats) in a healthy man, an increase in the number of CAG repeats may occur during the production of sperm cells, leading to affected offspring.
This is an extremely rare situation. If both of your parents carry an abnormal copy of the gene, your overall risk of inheriting the HD gene increases to 75%. You will have 25% risk of being homozygous, i.e. inheriting two abnormal copies of the gene. Homozygous individuals generally do not show an earlier symptom onset, but may have an increased rate of disease progression.
Yes, a few HD-like diseases (HDLD) have been described, although the genes responsible for these disorders are different from the one that causes HD. Moreover, the nature of these diseases and their symptoms are slightly different.