There are several movement disorders that affect the human body; some of these disorders are well known, like Parkinson’s Disease, Huntington’s Disease, Multiple System Atrophy, and Essential Tremor. Many of these disorders share overlapping symptoms and are often mistaken, as early onset or in later stages of life, for Parkinson’s disease. These similarities can include muscle stiffness or rigidity, tremors, gait, and balance problems. However, to the casual observer, the outward movements of the body may look alike, but the diseases behind them are not the same. 

What is the ADCY5-related disorder?

One of the rarest movement disorders that most of us have never heard of is known as the ADCY5-related disorder (ADCY5-RD) or ADCY5-related movement disorders. (ADCY5-RMD)  In an article posted on Neurology Journals – Pearls & Oy-sters: ADCY5-Related Dyskinesia,  “ADCY5-RD is described as a rare hyperkinetic movement disorder characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these resulting from pathogenic variants in the ADCY5 gene.” 

There isn’t a precise number of people worldwide who have this disease, but some estimates put the number of documented cases at 400 to 450. A study posted on the NIH’s National Library of Medicine puts the number at less than one case per million globally, suggesting a few thousand people worldwide at most, in part due to undocumented and undiagnosed cases. Some researchers feel that as genetic sequencing becomes more readily available, clinicians are identifying novel and atypical presentations, suggesting the real number may be higher than currently documented. Based on known cases compared with the global population, and running the numbers through AI, a conservative lower-bound estimate is roughly:

~1 in 10–20 million people

A simpler definition of the disease can be explained like this: ADCY5-RD is a movement disorder that typically begins in infancy, childhood, or teenage years due to a mutation in the ADCY5 gene. It causes involuntary hard-to-control movements such as jerking, twisting, or writhing motions, and sometimes muscle stiffness or sudden muscle spasms. A person only needs to inherit the genetic mutation from one parent to develop the condition, unlike other movement disorders, such as Wilson’s disease or Friedreich’s ataxia, and doesn’t require a family history of the disease to get it.

Diagnosis

 A paper published on the NIH’s National Center for Biotechnology Information website, ADCY5-related movement disorder are dignosised with a genetic test that looks for changes in the ADCY5 gene. Most people have one changed copy, while a small number have changes in both copies. The paper also states that “No consensus clinical diagnostic criteria for ADCY5-related movement disorder (ADCY5-MD) have been published.” They do offer “Suggestive Findings” that physicians and others should be on the lookout for; some of these are: Axial hypotonia and weakness, Lower-limb spasticity with pyramidal signs, delayed motor and speech development, persistence of dyskinesia during sleep, and more, as listed here.

Symptoms

ADCY5 is a movement disorder known as hyperkinetic, meaning when the body moves more than intended, often without the person trying to move at all. Common features of this disease are dance-like, flowing movements called Chorea, Dystonia (sustained muscle contractions and abnormal postures common in other disorders like Parkinson’s Disease, Multiple System Atrophy, and Huntington’s Disease), sudden jerking known as Myoclonus, and facial movements like grimacing and jaw movements.  Unlike other movement disorders, the symptoms of ADCY5-RD are closely related to sleep, often appearing when the body should be at rest. Researchers point out that these movements can be triggered by the “initial stages of NREM sleep, REM sleep, and/or by the sleep-wake transition.” Researchers also indicate symptoms may be triggered by drowsiness, awakenings, or several other conditions, such as concurrent illnesses, emotions, anxiety, stress, tiredness, laughter, sneezing, and/or medications.

What ADCY5 is Not

Unlike the previously mentioned movement disorders, ADCY5-RD is not neurodegenerative. It doesn’t cause progressive brain damage over time because it does not involve widespread loss of brain cells, even though the symptoms of this disease may lessen or worsen with time. Symptoms will increase when a person is exposed to triggers like stress, illiness or by experiencing sleep disruption. In technological terms, think of ADCY5-related disorder as a software problem rather than a hardware failure. The brain’s structure remains intact, but the signals controlling movement don’t always fire smoothly. The system isn’t breaking down; it’s misfiring.

Treatments 

Like many other movement disorders currently being diagnosed and managed, there is no known cure for this disease yet, but several treatment options are available that may reduce symptoms. Medications like Benzodiazepines (a class of medications designed to slow down overactive brain activity, reduce anxiety, relax muscles, and control seizures or severe muscle spasms), Anticholinergics (medications that reduce overactive nerve signals by blocking acetylcholine (a neurotransmitter), which help calm certain involuntary movements, muscle spasms, or tremors). 

Deep Brain Stimulation (DBS) is also being used as a treatment for patients who have severe, disabling symptoms and don’t respond well to medications, very similar to those with Parkinson’s Disease. DBS targets the globus pallidus internus (GPi) (a deep brain structure that helps control movement), which works by modulating abnormal brain signaling in regions involved in movement control, such as the basal ganglia. DBS is aimed at improving symptoms, not stopping disease progression. 

Some of the other treatments published on the NIH website include physical and occupational therapy, speech-language therapy, physical medicine and rehabilitation, and management of neurobehavioral/psychiatric manifestations by mental health professionals. 

ADCY5-related disorder illustrates how movement disorders are not all the same; those that look similar to the naked eye can be driven by very different disease processes underneath. As genetic testing becomes more widely available, more patients may be accurately diagnosed instead of being mistaken for more common conditions like Parkinson’s disease. While there is currently no cure for any of the movement disorders that are known to medicine, current treatments and therapies are aimed at improving symptoms, while researchers now explore whole body solutions in order to diagnose the underlying causes of many movement disorders and develop more targeted, effective treatments.

In technological terms, ADCY5-related disorder is best understood as a software problem rather than a hardware failure: the brain’s structure remains intact, but the signals controlling movement do not always fire smoothly. The system is not breaking down; it is misfiring, and understanding that difference is critical to how this disease is diagnosed, managed, and studied moving forward.

Find out more about what ADCY5 is and how the mutation in the gene works at https://www.adcy5.org/adcy5

^{Unless noted, all media by Chris Denny/Adobe}