The following is a proposal of changes to the current Huntington's disease criteria. This proposal will benefit patients who need a diagnosis of Huntington's disease when it is needed - services and support, without waiting or relying on chorea as the first manifested symptom. This proposal was written by Dr. Herwig Lange (George Huntington Institute, Germany), and supported by: Dr. Thomas Bird (Founder of University of Washington HDSA Center of Excellence), Dr. Travis Cruickshank (Edith Cowan University, Perth Australia), Dr. Matthias Dose (founder of Huntington-Zentrum Süd, Munich, Germany). Dr. Clare Eddy (Birmingham and Solihull Mental Health NHS Foundation Trust, England), Dr. Jane Paulsen (University of Wisconsin-Madison), Dr. Hugh Rickards (University of Birmingham, England), Dr. Adolf Weindl (Technische Universität München, Munich, Germany),
We must receive feedback from patients and families - globally. For change to happen, we must continue to have the participation of our incredible community. Following the proposal below, please participate in the short poll. Project CHANGE has given our patients and families a voice to demand change!
The HD mutation is present and active from the moment of conception, therefore there is no starting point of HD.
The HD mutation may not cause health problems until late in life or even never during a normal lifespan.
With increasing CAG repeats, the probability to develop symptoms increases, and the age of onset decreases.
HD causes changes in brain structure and function that can be measured years before clinical symptoms appear. Symptoms appear, when the brain cannot compensate for these changes in brain structure and function any longer, this is usually a gradual process with fluctuating states over many years.
The brain can compensate for these changes in brain function for many years (asymptomatic stage). This is the stage, in which disease-modifying therapies must start to prevent the appearance of symptoms.
HD can cause motor, cognitive, emotional, and vegetative symptoms.
No clinical symptom is specific to HD, so basing a diagnosis on a single symptom can be erroneous, even if the CAG expansion is present.
Depression is the most frequent psychiatric symptom and appears in the majority of HD patients, but can be present in non-carriers including partners. Even hyperkinetic movements are not necessarily symptoms of HD in persons at risk, as they can be present in non-carriers with other neurological and psychiatric disorders or as a consequence of medication.
Since HD often does not start with motor symptoms, but with cognitive, emotional, behavioral, or vegetative symptoms with implications for function at home and/or at work and quality of life, diagnosis of HD must be based on a thorough diagnostic work-up (motor, cognitive, psychiatric, behavioral, and functional aspects). So relevant diagnostic procedures (brain scans of structure, function, or metabolism, tests of brain function, cognitive tests, biomarkers in blood) are essential and must be explained and offered.
The diagnosis of HD is - clinical-biological. Without the expanded repeat (> 27 CAG) HD is not the cause of the health issues in that patient.
(1) Any diagnostic procedure, either predictive or clinical, can only be administered with the fully informed consent of the person seeking that information. All meaningful diagnostic and supportive procedures must be offered and performed at the person's wish, but no unwanted tests or procedures must be forced upon that person.
(2) It must be explained that the diagnosis of HD has far-reaching consequences for the entire family of the person requesting diagnostic information. It must also be explained that there is no specific moment of disease onset, but that HD is a continuous process from normal brain function to the clinical stage with gradually increasing disabilities.
(3) It must be explained to the person requesting diagnostic information that the fundamental diagnostic test is the molecular-genetic test of the CAG-repeat in the Htt-gene. Without the repeat expansion beyond the normal range being documented, no diagnosis of HD is definitive. So, if the size of the CAG-repeat is not known, measuring it is the first logical step in diagnosing HD.
(1) If the CAG-repeat-expansion beyond the normal range is not present, HD is excluded and other causes of symptoms demand thorough diagnostic work-up.
(2) If the CAG-repeat-expansion beyond the normal range is documented, HD should be diagnosed and staged according to the presence of MRI findings or other biomarkers, and clinical signs of HD (see below under diagnosis).
(1) If, based on the entire clinical diagnostic workup (motor, cognitive, psychiatric, behavioral, vegetative, and functional components), preferentially supported by diagnostic tests relevant for HD or to exclude other causes of the symptoms - it is more likely than unlikely that this patient has symptoms or signs that have occurred (partly or completely) as a result of HD pathology, in the presence of the expanded CAG-repeat a diagnosis of HD is the most likely and should be offered.
(2) The stages of HD must be explained.
(2.1) HD-mutation (CAG-expansion beyond normal range) not present: HD is excluded.
(2.2) HD-mutation (CAG-expansion beyond normal range) present:
Stage 0 - Premanifest: no signs or symptoms on the neurological and psychiatric exam and no functional limitations, normal findings in biomarkers.
Action: No action beyond a healthy lifestyle and avoidance of chronic stress.
Stage 1 - Presymptomatic: no signs or symptoms and no functional limitations, abnormal findings in biomarkers.
Action: In this stage, disease-modifying therapies must start to prevent or delay the onset of overt symptoms. Optimal
medical care for other medical conditions including dental care, nutrition, a healthy lifestyle, and avoidance of chronic stress.
Stage 2 - Initial Phase: Symptoms or signs without significant distress or functional limitations, abnormal findings in relevant biomarkers.
Action: Adequate support for patient and family, optimal medical care for other medical conditions incl. dental care and nutrition. Healthy lifestyle and avoidance of chronic stress.
Stage 3 - Clinical Phase: Symptoms or signs with significant distress or functional limitations, abnormal findings in relevant biomarkers. Staging (early, middle, advanced) according to functional limitations.
Action: all of the above plus symptom-oriented therapies (medications & exercises).
At all stages, information about therapeutic interventions, including lifestyle - esp. drugs and alcohol, rehab and exercises, cognitive and behavioral management, therapeutic trials, family planning, social and health services, lay organizations, and support groups, is essential for informed decisions and must be given. Adequate medical, psychological, social, and legal support must be available.
It is imperative that we receive feedback from patients and families - globally. Please participate in this short poll. Project CHANGE has given our patients and families a voice to demand change. For your privacy, only your country and answer are required. However, if you wish to complete the entire form, your information will not be shared. WeHaveAFace does not share personal information gathered for our international projects.