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|LETTER TO EDITOR
|Year : 2018 | Volume
| Issue : 7 | Page : 141-142
Mahesh Kamate, Nishant Mittal
Department of Pediatrics, KLE University's J N Medical College, Belgaum, Karnataka, India
|Date of Web Publication||1-Mar-2018|
Dr. Mahesh Kamate
Department of Pediatrics, KLE University's J N Medical College, Belgaum - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kamate M, Mittal N. ADCY5-related dyskinesia. Neurol India 2018;66, Suppl S1:141-2
Evaluating a child who is suffering from a developmental delay that is associated with abnormal limb movements, albeit with a normal neuroimaging, is difficult. Unfortunately, there are no characteristic clinical clues that may hint towards the existing diagnosis in most of these types of dyskinesias, except in a few types of dyskinesias that are associated with a diurnal variation with worsening in the evening. The latter may be a characteristic feature found in dihydroxyphenylalanine (DOPA)-responsive dystonias. Another genetic dyskinesia that may present with characteristic clinical clues is the adenylate cyclase (ADCY5) gene-related dyskinesias, which have a marked exacerbation during the period of drowsiness prior to sleeping, are associated with a prolonged latency during this period when the patient is trying to go off to sleep, and may especially occur during arousal from sleep.,,
A 12-year old boy, born to parents related by third-degree consanguinity, with a normal birth history, presented with delayed attainment of motor milestones as well as clumsiness, and abnormal movements of limbs. The abnormal movements were of maximum amplitude and frequency in the morning as soon as he woke up, lasted for 30–60 minutes, and then subsided on their own. After this period, he could perform his routine activities. The movements increased after the patient was sitting in a constant place for a long time, such as while undertaking long journeys and after episodes of illnesses. He was very restless in bed during his sleep, and his sleep would be extremely disturbed on most days. There was no family history of a similar illness. The child did not respond to treatment with medications like levodopa–carbidopa combination, high-dose trihexyphenidyl (30 mg per day), clonazepam, tetrabenazine, haloperidol, valproate, or carbamazepine. He had bilateral choreoathetosis with facial myokymia [Video 1]. From the age of 3 years, the child had been extensively examined at different neurological centres. Magnetic resonance imaging of the brain; tandem mass spectrometry; urine gas chromatography/mass spectrometry; serum lactate, ammonia, copper, ceruloplasmin as well as uric acid; and, renal and liver function tests were normal. Worsening of symptoms that occurred in the morning, the characteristic restlessness during sleep, and the associated facial myokymia suggested the presence of ADCY5-related dyskinesia. Blood was sent for assessment of the dystonia panel by next-generation sequencing, which revealed a heterozygous missense variation in exon-2 of the ADCY5 gene (chr: 3: 123071311;G.G/A; depth: 55x) that resulted in the amino acid substitution of tryptophan to arginine at codon 18 (C1252C>C/T). He was put on clonazepam and physiotherapy, which resulted in symptomatic improvement.
ADCY5-related dyskinesia is an infantile or childhood-onset disorder with a wide range of mixed hyperkinetic abnormal movements that include dystonia, chorea, tremors, and myoclonus, often with facial involvement., Most patients also have associated axial hypotonia. The triggering factors for worsening of the clinical symptomatology include prolonged periods of inactivity, fatigue, anxiety, concurrent illnesses, or other stressors. The episodes may wax and wane over weeks to months. The dyskinesias become continuous or constant with increasing age, but the involuntary movements could still be absent during the rest phase of the illness., There are characteristic episodes of exacerbation of dyskinesias, which may also serve to interrupt sleep. The patients characteristically have dyskinesias during the interim period of drowsiness prior to sleeping, that often prevents the initiation of sleep so that the patient may sometimes lie writhing for hours after retiring to bed; some studies have reported dyskinesias associated with awakening in the early morning after sleep.
ADCY5 dyskinesia is caused by a gain of functional mutations in the ADCY-5 gene that integrates signals from multiple receptors, including the D1 and D2 striatal dopamine receptors. Clonazepam and clobazam have an indirect inhibitory effect on adenylyl cyclase-5 activity, potentially counteracting the gain of function that has been shown to occur due to the mutation.,
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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