January 9, 2025

Snika Gupta 

11th Grade

Brooklyn Technical High School

Introduction

Huntington’s Disease is an inherited genetic disease that causes neurons to die over time, hindering a person's movement, thinking, and mental health. It primarily affects parts of the brain that control intentional motion leading to physical symptoms such as chorea, dystonia, and akathisia. The disease usually appears in adults from the age of 30 to 50 (adult-onset HD) but can appear in children (juvenile HD). As the disease progresses, its symptoms worsen. It begins with uncontrolled movements appearing in a person's extremities and torsos, which become more severe when the person is nervous and distracted. 

Symptoms

Some early signs include mild clumsiness, issues with balance and movement, changes in a person's behavior, and cognitive issues. In some people, chorea is not a symptom; instead, they become rigid and move very little or not at all which is referred to as akinesia. On the other hand, some start with chorea and become more rigid over time. Another symptom is dystonia, which causes unchanged and unusual posture. Dystonia can blend or alternate with akinesia. 

Later symptoms can include slurred speech and difficulties with swallowing, speaking, walking, feeding, and eating. The problems with swallowing are what leads to weight loss. Psychological symptoms include insomnia, loss of energy, fatigue, and seizures. If the symptoms progress significantly, the condition is described as dementia. 

Inheritance

Huntington's disease is passed down through a mutation in a specific gene on chromosome 4. It is passed from parent to child but can sometimes skip a generation.  It is inherited in an autosomal dominant pattern, meaning that a parent with the HD gene has a 50% chance of passing it to their child. If the disease develops without a prior family history, it is referred to as sporadic HD. 

HD is caused by a mutation in the gene for Huntingtin. This mutation causes CAG—DNA building blocks made of cytosine, adenine, and guanine—to repeat much more often than they are meant to. If there are 36 or more CAGs, HD is prevalent in a person. When there are 27-35 CAGs, HD is not likely to develop but can be passed on to their children. Most people though, have less than 37 CAG that are linked and have no risk of developing HD. 

The excess repeats of CAGs leads to an enlarged glutamine fragment in the protein. The increase in the size of the protein leads to the creation of the Huntingtin protein to accumulate in the brain. The long proteins are broken up into smaller, toxic parts to combine and aggregate in neurons. The disruption in the function of the neurons causes the death of neurons. The stretch of the CAG repeats becomes longer as you age which amplifies the effect of the disease. 

Diagnosis 

Diagnosing HD begins with a neurological exam and a review of the patient's medical and family history. There is also a physical exam to examine the patient's senses (balance, reflexes, muscle tone, hearing, speaking, walking, movement, and mental status). Genetic testing is also done to confirm or deny HD. Genetic testing can also predict with more certainty if HD will develop and prenatal testing can also help see if they have HD. The direct genetic tests use a blood sample and count the number of CAG (36 repeats or more confirm the disease and 26 or less rule out HD as a diagnosis). If genetic testing and the review of family history do not confirm anything they are referred to other specialists to support the diagnosis. They also use CT and MRI scans to do brain imaging to determine the diagnosis. Scans may show shrinkage in parts of the brain and larger fluid-filled cavities. This is not the most conclusive test as these results come up in other disorders. Huntington's Disease can be hard to diagnose with its various symptoms and unusual presentations of the disease.

There is no cure for HD or treatment to reverse HD’s effects. Drugs such as tetrabenazine and Antipsychotic are used to treat and calm chorea. Antipsychotic drugs are used to particularly calm chorea down but can also cause side effects in HD patients such as hallucinations. Many also receive drugs for anxiety and depression due to the effects of drug treatment.