Huntington's disease-like

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Huntington's disease-like (HDL) is a group of related neurological conditions. As the name suggests, HDLs resembles Huntington's disease. HDLs and Huntington's disease are both characterized by uncontrolled movements, emotional problems, and loss of thinking ability. In both conditions these signs and symptoms worsen over time. HDLs occurs in people with the characteristic features of Huntington's disease who do not have a variant (also called mutation) in the gene typically associated with that disorder. Researchers have described four HDLs that are designated Huntington's disease-like 1 (HDL1) through Huntington's disease-like 4 (HDL4). Sometimes, HDL4 is also known as spinocerebellar ataxia type 17 (SCA17).

HDL1, HDL2, and HDL4 usually begin in early to mid-adulthood, although they can start earlier or later. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements (dyskinesia), poor coordination, and trouble learning new information or making decisions. Many people with an HDL develop involuntary jerking or twitching movements known as chorea. Over time, these abnormal movements worsen. Affected individuals may develop problems with walking (bradykinesia), speaking (dysarthria), and swallowing (dysphagia). People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities (dementia). Individuals with an HDL syndrome can live for 10 to 20 years after signs and symptoms begin, though this can vary between the types of HDL syndromes.

HDL3 begins much earlier in life than the other HDLs (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has some different signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDLs.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants in the PRNP, JPH3, and TBP genes have been found to cause the various HDLs. HDL1 is caused by variants in the PRNP gene, while HDL2 is caused by variants in JPH3. Variants in the TBP gene are responsible for HDL4. The genetic cause of HDL3 is unknown. These variants may account for some of the people with characteristic features of Huntington's disease who do not have a variant in the gene typically associated with that disorder.

The PRNP, JPH3, and TBP genes provide instructions for making proteins that are important for normal brain function. The features of HDLs result from a particular type of variant in any one of these genes. Normally, these genes contain a segment of DNA that repeats multiple times in a row. The variants that cause HDLs increase the length of these repeated segments. This type of variant leads to the production of an abnormal PRNP, JPH3, or TBP protein. As a result, there is a loss in normal protein activity. Additionally, the abnormal protein can build up in nerve cells (neurons) and disrupt the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of each HDL.

Many other medical conditions may also cause signs and symptoms that resemble those seen in people with Huntington's disease. This can make it difficult to accurately diagnose these conditions.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

HDL1, HDL2, and HDL4 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases of HDLs, an affected person has one parent with the condition.

HDL2 and HDL4 generally begin earlier in life and have more severe symptoms as the variants that cause these disorders are passed down from one generation to the next. This phenomenon is known as anticipation. Anticipation is caused by an increase in the length of an unstable region in the gene.

HDL3 is probably inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Overall, HDLs are rare. They are much less common than Huntington's disease, which affects an estimated 3 to 7 per 100,000 people of European ancestry.

Of the four described HDLs, HDL4 appears to be the most common. HDL2 is the second most common and occurs almost exclusively in people of African ancestry (especially Black South Africans).

Which doctor should you see?

The suggested department for discussing Huntington's disease-like is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Huntington's disease-like. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.