Research has uncovered a mechanism by which the genetic mutation that causes Huntington’s disease (HD) leads to brain cell death, but patients with the disease can still be misdiagnosed.

Handsaker RE, Kashin S, Reed NM, et al. Long somatic DNA-repeat expansion drives neurodegeneration in Huntington’s disease. Cell. 2025;188(3):623–639.

Mustafa FA. Misdiagnosis of Huntington’s disease. Correspondence. 2017;4(1):21.

 

Those with HD can experience uncontrollable movements and problems with emotions, cognition, personality, and behavior, but they may receive an incorrect diagnosis.

NIH. Huntington’s Disease. December 12, 2024.

 

“Huntington’s disease is a protean disease; it can take many different forms. People often think first of the movement issues, but changes in cognition and psychiatric symptoms are often the first to arise, and these can often be misdiagnosed as schizophrenia. Often patients have issues with behavioral control that lead to problems with addiction or [substance] abuse. This can destroy families and sometimes leave patients without any social support—or even homeless,” says Xenos Mason, MD, a neurologist at Keck Medicine of USC who specialises in movement disorders.

“As you can imagine, this creates a situation where there’s a lot of stigma and assumptions that can cloud the objectivity of doctors and even specialists. Once the diagnosis is made, it often seems obvious in retrospect, but it can be difficult for people to take that objective standpoint and look at the big picture,” he adds.

 

 

Symptoms misdiagnosed

 

While some symptoms, like chorea (uncontrollable dance-like movements), can be indicative of HD, they can also be dismissed or mistaken for other things.

NIH. Huntington’s Disease. December 12, 2024.

 

“Early in the disease, subtle chorea can sometimes be mistaken for restlessness, fidgeting, clumsiness associated with anxiety, or tics. Additionally, adaptations that patients make to try to mask or control their chorea (called parakinesis) can sometimes make it difficult for clinicians to recognise the early signs of HD,” Hengameh Zahed, MD, PhD, a neurologist at Stanford Medicine Movement Disorders Center, tells MDLinx.

 

“Another scenario is where psychiatric symptoms predominate and patients present with psychosis, suicidality, severe depression … with [the] presence of fairly subtle classic motor manifestations, such as chorea, or where the hyperkinetic movements get confused for another entity such as functional symptoms, malingering, tardive dyskinesia, or a drug-induced movement disorder,” Dr. Zahed adds.

 

The role of family history

 

Both Drs. Zahed and Mason note that a family history of HD—or the lack thereof—is important context.

 

Huntington’s disease is most likely to be misdiagnosed in the absence of a family history of the disease, Dr. Zahed says.

“This can happen for a variety of reasons: non-paternity; adoption; the early death of the affected parent; small families where another affected family member may not be known; the next generation presents symptoms at a much younger age, while the parent had minimal to no symptoms even in older age. In these cases, sometimes the possibility of a genetic aetiology gets discounted,” Dr. Zahed notes.

It’s important to remember that the absence of a known family history does not rule out the possibility of a genetic cause.

“Since at this time there are no disease-modifying treatments for HD, missing the diagnosis is not dangerous, per se. However, missing the diagnosis can lead to untreated symptoms and worse quality of life. Also, because HD has implications for the family, a missed diagnosis can result in missed opportunities for awareness and family planning. If disease-modifying treatments become available, then the danger in misdiagnosing [HD] becomes greater,” Dr. Zahed concludes.