Huntington's disease is characterized by a triad of symptoms: motor, psychiatric and cognitive. Symptoms, as well as their intensity and presentation, vary greatly from patient to patient. Clinical manifestations of the disease usually appear between the ages of 30 and 50, but the disease can be expressed at any age, from childhood or old age, before the age of 20 in 10% of cases, for example. Motor symptoms are the most visible and often the first to be identified, but cognitive or psychiatric problems may already be present. In the early stages, before the age of 20, the disease manifests itself mainly as behavioural and learning disorders. Huntington’s disease progresses, on average, over a period of 13 to 15 years after the onset of clinical symptoms, although this figure varies greatly from patient to patient, to severe dementia, an inability to walk and swallow, and ultimately death.
The diagnosis of Huntington's disease
Clinical diagnosis of Huntington's disease is made on the basis of symptoms presented by the patient, such as abnormal movements or behavioural problems, taking into account the family history that could guide such diagnosis. Brain imaging may rule out other pathologies with similar symptoms.
The clinical diagnosis of the disease can be confirmed by a genetic test that identifies expansion in the Huntingtin gene, carried out after genetic counselling of the signature of an informed consent to the restitution of results during a genetic consultation.
This molecular diagnosis is made from the DNA of blood cells and consists of quantifying the number of repeats of the CAG sequence.
Because of its hereditary transmission, the pre-symptomatic genetic test can be requested by family members of a person with Huntington’s disease. This genetic test allows loved ones to know whether or not they carry the disease and therefore whether they will ever develop it.
Currently, there are an estimated 12 000 people in France who carry a mutation in the huntingtin gene but do not yet have symptoms. This test is framed to allow the person to make the decision whether or not to test at the right time. It is a multidisciplinary consultation involving geneticist, neurologist, psychologist, genetic counsellor and nurse.
Once the gene and/or mutation responsible is known, the family can access genetic tests and expert advice on how the disease is transmitted within the family. It is now 30 years since we set up a consultation with Josué Feingold and Marcela Gargiulo at the Pitié-Salpêtrière hospital for people at risk for a disease they know. Their parents and grandparents are affected and they know they are at risk of developing it, perhaps one day. When the genetic variation responsible for the disease can be detected, there is a choice: to know or not to know before the disease begins.
Sometimes prenatal diagnosis may be requested. It is carried out by anticipating a future pregnancy to detect the presence of expansion in the foetus, before the end of the 3rd month. In the event of an unfavourable result, a medical termination of pregnancy may be carried out. Similarly, a pre-implantation diagnosis may also be performed. It consists of looking for the presence of expansion in embryos of two or three days old obtained by in vitro fertilisation (with all the limitations due to this technique (20% success). Unscathed embryos can then be implanted.
The CHU Pitié-Salpêtrière’s Medical Genetics Department specializes in hereditary diseases and offers consultations, from the prenatal period to adulthood, diagnosis, follow-up and genetic counselling (including pre-symptomatic and prenatal diagnosis), for sick persons and/or their relatives.
Identifying the factors that influence the age of onset of disease symptoms and its progression is at the heart of the Brain Institute’s research.
Alexandra Durr’s team at Paris Brain Institute has conducted and participated in several studies that have identified genetic variants influencing the progression of Huntington’s disease.
