ADCY5-Related Dyskinesia

Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about ADCY5-related dyskinesia is not fully understood. Several factors including the small number of identified patients, the lack of large clinical studies, and the possibility of other genes or additional factors influencing the disorder, prevent physicians from developing a complete picture of associated symptoms and prognosis?. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below.

All affected individuals have episodes of abnormal, uncontrolled movements especially affecting the arms and legs, face, or neck. These movements can be choreiform, myoclonic, or dystonic. Choreiform movements are continuous rapid, jerky, and sometimes writhing (athetotic) movements. Myoclonic movements are rapid, brief muscle contractions that cause sudden jerky or twitching movements. Dystonic movements are characterized by sustained and sometimes repetitive muscle contractions leading to muscle spasms and abnormal postures. Abnormal movements can occur continuously during the day and, sometimes, can occur at night disturbing sleep. Disrupted sleep can result in fatigue? and sleepiness during the day. Some individuals experience ballistic (large amplitude) movements at night or upon waking. Ballism is the abrupt contraction of muscles, particularly those of arm and leg muscles causing flailing, swinging movements of the arms and legs.

Abnormal movements are more common when affected individuals attempt to make deliberate, voluntary movements such as changing positions or reaching for things. Episodes of abnormal movements can be worsened or triggered by anxiety or stress. In some individuals, the disorder is worsened when drowsy or tired. In some people, episodes or symptoms are more common or worse in the morning. Prolonged inactivity, excitement, and being sick have also been reported as possible triggers. Abnormal movements can be painful, but some are not.

The onset of abnormal movements usually occurs during infancy, childhood, or throughout the teen-aged years. During infancy, affected infants may experience diminished muscle tone (hypotonia), particularly affecting the trunk, which is all of the body except for the head and arms, and legs (axial hypotonia). These infants may be described as being “floppy.” Some affected infants have had difficulty swallowing (dysarthria), while others have been described as extremely irritable. As affected infants and children age, there may be delays in attaining developmental milestones, especially motor milestones like crawling, sitting up, or walking because of the abnormal movements. In severely-affected individuals, abnormal movements may make walking extremely difficult requiring assistance to walk or the use of an ambulatory device such as a wheelchair. Mildly-affected individuals may have little problems walking but may appear a little clumsy. Some affected individuals will walk but have a slow, uncoordinated manner of walking (abnormal gait), while others may fall frequently. Axial hypotonia improves with age. Although, in some individuals, residual diminished muscle tone affecting the neck (cervical? hypotonia) can remain. Cervical hypotonia can cause the head to droop or hang toward the chest (neck flexion).

A characteristic finding that occurs in some affected individuals is facial twitching. Mild abnormal movements including those of facial muscles can result in frustration or awkwardness in social situations. Facial twitching usually involves the muscles around the eyes and mouth. In some instances, facial twitching in infants and young children can lead to delays in attaining speech and/or difficulty being understood due to poor articulation (dysarthria). Some individuals have difficulty staring at a fixed object (gaze persistence) and also experience oculomotor apraxia, in which problems are moving the eyes voluntarily.

How the disorder affects people over time can be very different. Movement disorders may be continual or may come and go (episodic). They can last from a few seconds to hours or longer. Their frequency and duration can change over time. Some affected individuals have long periods where the symptoms go away (remission?). For some people, symptoms remain generally stable throughout life. Sometimes, symptoms get slowly worse during childhood and adolescence before stabilizing; in other people, the disorder has gone into remission in the teenage years. Several reports state that in many people symptoms improved on their own during middle age.

There have been reports of heart (cardiac) abnormalities in some affected individuals. It is not yet known whether these heart abnormalities are potential complications of the disorder or coincidental findings. Some researchers have speculated as to whether neuropsychiatric abnormalities like depression, anxiety, and psychosis are also complications of this disorder. More research is necessary to fully understand the complex and highly variable signs and symptoms associated with ADCY5-related dyskinesia.