What Is ADCY5-Related Dyskinesia?
ADCY5-related dyskinesia is a very rare neurologic disorder with different types of movement abnormalities. The term "dyskinesia" refers to sudden abnormal involuntary movements occurring in the affected individuals. Involuntary movements are any uncontrolled movements an individual may experience, such as sudden jerks, twitches, twisting, writhing motions, or tremors. The commonly affected body parts include the arms, legs, neck, and face.
The symptoms of ADCY5-related dyskinesia usually start between infancy and late adolescence and continue throughout life. However, there may be no symptoms called remission in certain lifetime periods. These symptoms can occur continually during the day and sleep, which can get disturbed due to the symptoms.
Sudden, unexpected movements can be noted during changing positions, such as standing or sitting. In mild cases of ADCY5-related dyskinesia, walking, and other motor skills may be affected. In severe cases of ADCY5-related dyskinesia, individuals may experience weak muscle tone, developmental delays, and even find it difficult to do daily activities and, in due course, may require a wheelchair.
Changes in the ADCY5 gene generally cause ADCY5-related dyskinesia. This mutated gene may be inherited from a parent or can occur as a new variation without any family history. Individuals with this condition have a normal level of intelligence; their life expectancy is not affected by this condition. The management of ADCY5-related dyskinesia is based on the presenting illness in each person and may include physical therapy, medications, and occupational therapy.
What Causes ADCY5-Related Dyskinesia?
Changes in the ADCY5 gene mainly cause ADCY5-related dyskinesia. This gene is responsible for providing information for producing an enzyme called adenylate cyclase 5, which plays an important role in many body functions. When any abnormal changes occur in the gene, there will be abnormalities in enzyme production. Depending on the functions of the particular enzyme, any body organ system can be affected, including the brain.
ADCY5-related dyskinesia can be passed on from any of the parents or due to a new mutation. A new mutation results from abnormal changes occurring in the gene during egg or sperm formation, so it is not passed on from parents, and other family members will be affected by this condition.
What Are the Signs and Symptoms of ADCY5-Related Dyskinesia?
The signs and symptoms of ADCY5‐related dyskinesia may vary significantly among affected individuals. The severity and type of symptoms may also vary for each individual. As complete knowledge about the disease is unknown, more studies are required to determine the possibility of other genes or other factors influencing the disorder. These factors prevent healthcare professionals from creating complete data on associated symptoms and prognosis. Therefore, affected individuals may or may not have all of the following symptoms:
All affected individuals have abnormal, uncontrolled movements, mainly affecting the face, neck, arms, and legs. They can be on and off during the day and less frequent during sleep. The onset of abnormal movements generally occurs during early childhood or the teenage years. These movements can be myoclonic, choreiform, or dystonic.
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Choreiform Movements - Continuous rapid, jerky, and writhing movements.
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Myoclonic Movements - Brief and rapid muscle contractions cause sudden jerky movements.
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Dystonic Movements - Repetitive muscle contractions cause muscle spasms and abnormal postures.
Fatigue - Due to abnormal movements at night, fatigue ,and sleepiness can occur during the day.
Ballism - Sudden contraction of muscles, especially arms and legs. This can lead to flailing or swinging movements of the extremities.
Hypotonia - It can cause diminished muscle tone in infants, leading to developmental delays.
Dysarthria - The individuals may have difficulty speaking and swallowing due to weakness of the muscles involved in speaking and swallowing.
Developmental Delays - The affected infants may have developmental delays in their milestones, like crawling and walking, due to the abnormal movements. In severe cases, walking may not be possible, and the child may require assistance or a wheelchair to move around.
Abnormal Gait - In mild cases, the individual may be able to walk, but the gait may be clumsy and have an uncoordinated manner of walking.
Facial Twitching - It is a characteristic finding in individuals affected by ADCY5-related dyskinesia. Usually, muscles around the eyes and mouth may be involved in facial twitching, and it may be irritating or frustrating in social situations. Slurred speech can result from facial twitching in infants and children.
Cardiac Abnormalities - In some affected individuals, heart abnormalities have been reported. It is unclear whether these heart abnormalities are complications of the condition or coincidental findings.
How Is ADCY5-Related Dyskinesia Diagnosed?
A diagnosis of ADCY5-related dyskinesia is mainly based on evaluating the signs and symptoms. A diagnosis is suspected in patients with characteristic movement disorder but without structural abnormalities in the brain. A detailed patient and family history and clinical evaluation are performed. A variety of specialized tests should also be done to confirm ADCY5-related dyskinesia.
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Imaging Tests - Specialized imaging such as computerized tomography (CT) scanning and magnetic resonance imaging (MRI) will be performed to check for abnormalities.
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Genetic Testing - It can be done to detect disease-causing mutations in the ADCY5 gene. Blood samples of the affected individuals are collected and sent to the laboratory to undergo whole exome sequencing (WES). WES is a testing method that checks for the genes that contain instructions for creating proteins.
How Is ADCY5-Related Dyskinesia Treated?
The treatment for ADCY5‐related dyskinesia is completely based on the specific symptoms of each affected individual. Treatment may require the coordinated approach of different specialists. Pediatricians, neurologists, speech therapists, physical therapists, ophthalmologists, occupational therapists, and other healthcare professionals should all be involved in systematically and comprehensively making a treatment plan. Genetic counseling is also helpful for affected individuals and their families.
Conclusion:
ADCY5‐related dyskinesia is a very rare neurological disorder affecting the movement of the body. Individuals affected by this disorder may face various types of movement disorders that can affect their daily routines. The diagnosis is based on the presenting illness and the treatment is also tailored according to the presenting illness by a team of doctors.
