Author: Martha Nance, MD
Struthers Parkinson’s Center, Golden Valley, MN, and Huntington Disease Society of America HD Center of Excellence, Hennepin HealthCare, Minneapolis, MN

Reviewed: September 2022

SUMMARY

Huntington’s disease (HD) is a genetic disease. It usually affects adults. HD is neurodegenerative. This means that some cells in the brain do not work properly. Later, those brain cells die. It causes:

• Progressive loss of thinking skills (dementia)
• Loss of coordination
• Involuntary movements (chorea)
• Muscle stiffness (dystonia)
• Psychological and behavioral symptoms (in some cases)

Huntington’s disease typically begins in adulthood. However, symptoms can begin in people younger than eighteen years. In these cases, it is called “juvenile-onset Huntington’s disease” (JoHD).

Symptoms progress over five to twenty years until death. Treatment is focused on managing symptoms. There is no treatment that slows, stops, or reverses the progression of the disease.

JoHD is always caused by a mutation in a particular gene. The affected gene is called huntingtin (HTT). The mutation is called a “CAG repeat expansion.” The “word” CAG tells the cell to add a chemical, called glutamine, to the protein that it is making. Since the huntingtin protein is important in nerve cells in the brain, the symptoms of JoHD are mostly neurological.

This mutation is passed on from parent to child. So, any biological child of a person with HD has a 50% chance of:

• Inheriting the abnormal gene
• Developing HD

The size of the mutation is one factor that determines when symptoms begin. Children with JoHD tend to have larger mutations than people with adult-onset HD.

HD affects about one in every 10,000 people in the United States. About 5–10% of people with HD have JoHD.

Disorder Overview

DESCRIPTION

Children with JoHD develop normally before birth. They have a normal delivery and early development. However, then the abnormal gene begins to affect them. The nerve cells in certain parts of the brain begin to function poorly. Gradually, the brain cells die.

This process begins in control centers deep in the brain. These centers are called the caudate nucleus and the putamen. It gradually spreads to involve cells throughout the brain.

Symptoms and management can vary depending on the age of the affected child. So, clinicians sometimes split pediatric HD into two categories. These are:

The damage and loss of nerve cells progresses over the years. It leads to a progressive decline in thinking and movement, among many other symptoms.

There is no cure for JoHD. Unfortunately, all children diagnosed with JoHD die with the disease. Most die because of complications of the disease. This typically occurs five to twenty years after symptoms start.

SIGNS AND SYMPTOMS

In children with childhood-onset HD, common symptoms at the onset include:

• Stiffness (rigidity) of the trunk or limbs. This can sometimes lead to a stiff gait or falling.
• Abnormal postures of the head and neck or limbs (dystonia)
• Tremors
• Slurring of speech (dysarthria) and drooling
• Loss of previously attained motor skills. Depending on the age, this could include:
  • Running
  • Kicking
  • Throwing
  • Riding a bicycle
  • Handling utensils
• Decline in thinking (cognitive) skills. This may manifest as a decline in school performance.
• Attention problems. Such problems can resemble attention deficit disorder.
• Behavior problems, which can range from mild to very severe

In an older child with adolescent-onset HD, common initial symptoms include:

• Involuntary dance-like movements (chorea)
• Stiffness and abnormal postures (rigidity and dystonia)
• Changes in school performance
• Behavior problems, which can range from mild to very severe
• Mood changes, such as depression and anxiety

Additional symptoms that occur in over 50% of children with JoHD include:

• Sleep disturbance (insomnia)
• Tics (brief involuntary movements)
• Pain
• Itching (pruritis)

Additional symptoms that occur in 25–50% of children with JoHD include:

• Psychosis
• Suicidal thinking
• Seizures
• Involuntary twitching or jerking (myoclonus)
• Increased heart rate (usually of no clinical significance)

CAUSES

Both HD and JoHD are caused by a CAG repeat expansion in the HTT gene. No other kind of mutation in the gene causes HD.

The size of the mutation can increase as the abnormal gene passes from parent to child. Larger mutations are associated with an earlier onset of symptoms.

CAG repeat lengths of thirty-five or less are normal. Lengths of thirty-six and above can cause HD. Most people with adult-onset HD have CAG repeat lengths of thirty-six to fifty. Most people with JoHD have CAG repeat lengths of fifty-five or more.

Rare exceptions to all of the statements in the previous paragraph have been reported.

LABORATORY INVESTIGATIONS

A family history can help lead towards an HD diagnosis. A parent (usually the father), sibling, aunt/uncle, or grandparent may also have HD.

Clinicians often follow patients over six to twenty-four months, rather than ordering a gene test immediately. They monitor whether symptoms progress despite appropriate treatment. If so, they order a gene test.

The final diagnosis of JoHD is made based on the clinical exam. This is confirmed by a gene test. The test looks for a CAG repeat expansion in the HTT gene.

A genetic test can confirm the presence of the CAG repeat expansion that causes HD. However, it does not prove that HD is the cause of symptoms.

Mutations in certain other genes can lead to similar symptoms. For this reason, additional genetic testing may be appropriate. A doctor may order such tests if they suspect a person of having HD but they have a normal HD gene test.

The symptoms of HD can overlap with those of many other conditions. This makes it difficult to diagnose JoHD. The clinician may order tests to rule out other conditions. Tests also allow them to determine the severity of HD.

Depending on the child and the symptoms, these tests could include:

• Blood tests. These can rule out:
  • Thyroid conditions
  • Vitamin deficiencies

They can also assess the function of:

• The kidney
• The liver
• The blood
• Urine tests. These can rule out other rare genetic conditions. They can also screen for illicit drug use.
• A spinal tap (lumbar puncture)
• Magnetic resonance imaging (MRI) of the brain

Referrals to specialists may be important for both diagnosis and management. The pediatrician may refer the child to:

• A child neurologist
• A movement disorders specialist
• An HD specialist
• A psychiatrist
• A neuropsychologist (for formal cognitive assessment)
• A psychologist
• A speech-language pathologist
• A physical therapist
• A geneticist or genetic counselor

The following do not have to be repeated during the course of HD:

• Genetic testing
• Brain imaging
• Laboratory testing

However, a particular situation may require additional testing.

TREATMENT AND THERAPIES

JoHD is best managed by a team of:

• Healthcare providers
• School services and programs
• Community social services

In a person with HD, the following decline over time:

• Physical capabilities
• Cognitive/mental capabilities

So, an independent education program (IEP) for the school is necessary. The child should be reassessed every year.

The healthcare team should assist by performing annual or semi-annual assessments. The team could include:

• A pediatrician
• A dentist
• A child neurologist
• A child psychiatrist
• A neuropsychologist
• A psychologist
• A speech-language pathologist
• A physical therapist
• An occupational therapist
• A dietitian
• A social worker
• A pharmacist

In the later stages of the disease, additional types of care may include:

• Physical medicine/rehabilitation
• Gastroenterology
• Palliative care
• Hospice

In addition to the progression of core symptoms, symptoms such as insomnia and seizures may be severe. They can require treatment.

OUTLOOK

All children with HD will eventually progress to the late stage of the disease.

In the early and mid-stages of the disease, families and the medical team focus on:

• Symptom management
• Good nutrition
• General medical and dental care

They also aim to optimize the opportunity for:

• Cognitive activities
• Social interaction
• Physical activity
• Active participation

The goal is for the affected child to participate in school, community, and family activities.

Optimal care often includes medical care and support for other family members.

They may have HD or other health issues themselves. They may be managing a spouse and/or other children with HD as well. Many could benefit from support at they try to work and manage a challenging home situation at the same time.

In the later stages of JoHD, the goals of care typically evolve to a more supportive approach. An affected child will eventually be unable to walk. So, equipment and home modifications will be necessary. They may need to accommodate:

• A wheelchair
• A lift device
• A hospital bed

Some parents find it helpful to have in-home help. Particularly, they can benefit from help with activities like:

• Bathing
• Dressing
• Physical therapy

Eating becomes more difficult. So, patients can be at risk of choking. Families must decide whether to use a gastrostomy feeding tube to assist with the administration of:

• Nutrition
• Fluids
• Medication

Children with HD may be young adults when they reach the late stages. It is important for parents to consider the transition in advance. That way, it goes as smoothly as possible. A transition in medical care providers and out of the school system will be necessary.

In some communities, there are “complex care management” programs. Your local or regional Children’s Hospital may offer these. There may also be “community-based palliative care” programs. These can help families as the child moves to the later stages.

In the terminal weeks of the disease, many families find the use of a hospice care team to be invaluable. They can provide practical and emotional support as they navigate a difficult but expected stage of the child’s disease.

Children with HD may have the opportunity to participate in observational or interventional research studies. HD patient and family organizations may have information about current or upcoming research studies.

RELATED DISORDERS

Other conditions can mimic some of the symptoms of JoHD. These include:

• Depression
• Attention deficit disorder
• Tic disorders
• Alcohol and drug abuse

These can all reproduce some of the features of this disease. Normal adolescence can too.

However, if we include progression of cognitive and motor dysfunction as defining features of JoHD, the list shortens. Then it only includes a few other rare genetic conditions, such as the hereditary ataxias.

Particularly, these can have similar symptoms:

• Dentatorubral-pallidoluysian atrophy (DRPLA)
• Spinocerebellar ataxia types 2, 3, and 17
• Neuronal brain degeneration with iron accumulation (NBIA) disorders

All these genetic conditions can be diagnosed with additional genetic testing.

Rarely, nongenetic conditions can cause some of the features of JoHD. However, the time course differs greatly. They can progress over days (brain infections) or weeks (autoimmune encephalopathies). Brain imaging and spinal fluid analysis would lead to a diagnosis.

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Research 

ClinicalTrials.gov for Huntington’s Disease (birth to 17 years).

These are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently. 

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.    

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits. 

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

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Quigley J. Juvenile Huntington’s Disease: Diagnostic and Treatment Considerations for the Psychiatrist. Curr Psychiatry Rep. 2017 Feb;19(2):9. https://doi.org/10.1007/s11920-017-0759-9. PMID: 28168595.

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Juvenile Huntington [Internet]. Clinicaltrials.gov [accessed 2022 July 28]. Available from: https://clinicaltrials.gov/ct2/results?cond=juvenile+huntington&term=&cntry=&state=&city=&dist=