Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study.

Aim: Chromosome microarray (CMA) can determine copy number variants such as microdeletions or microduplications. Microdeletions of movement disorder genes including epsilon-sarcoglycan (SGCE) and thyroid transcription factor-1 (TITF1) have been described in patients with myoclonus dystonia and benign hereditary chorea respectively. We examined whether CMA is a valuable tool in the investigation of children with suspected genetic movement disorders.

Method: A genetic movement disorder was suspected if there was a positive first-degree family history, or two or more of the following factors: normal or near-normal magnetic resonance imaging, negative history of brain injury, and negative investigations for metabolic disorders. Tic disorders were excluded. Twenty-five patients (18 males, seven females) with a mean age at movement disorder onset of 4 years 5 month (range 1 mo-14 y) were prospectively recruited with the following primary movement disorders: dystonia (n=10), paroxysmal kinesigenic dyskinesia (n=5), tremor (n=4), chorea (n=3), myoclonus (n=2), and paroxysmal non-kinesigenic dyskinesia (n=1). Comorbid associated features were common, particularly developmental delay or intellectual disability (19 out of 25) and attention-deficit-hyperactivity disorder (six out of 25). CMA was performed using Agilent aCGH 60K array.

Results: Seven out of twenty-five patients had a microdeletion determined by CMA. None of the microdeletions were considered benign variants. Four patients had a deletion of a known movement disorder gene including paroxysmal kinesigenic dyskinesia (PRRT2; n=2), SGCE (myoclonus dystonia, n=1), and TITF1 (benign hereditary chorea, n=1). Three patients had novel microdeletions of unknown but potential significance including 14q13.3 (chorea, n=1), 19p13.12 (tremor, n=1), and 19q13.12 (progressive dystonia). All seven patients had associated neurodevelopmental or behavioural problems.

Interpretation: Assays that determine copy number variants may be a valuable first-tier investigation in patients with suspected genetic movement disorders, particularly when associated with intellectual disability or developmental disorders. Microdeletion syndromes may help the search for new movement disorder genes.