Subcortical Myoclonus and Associated Dystonia in 22q11.2 Deletion Syndrome

• Published in: Tremor and other hyperkinetic movements (New York, N.Y.) N.Y.), 2020, Vol.10
• Main Authors: Van Iseghem, Vincent, McGovern, Eavan, Apartis, Emmanuelle, Keren, Boris, Vidailhet, Marie, Roze, Emmanuel, Degos, Bertrand
• Format: Article
• Language: English
• Subjects: Antipsychotics; Dopamine; Dystonia; Epilepsy; Genes; Magnetic resonance imaging; Movement disorders; Patients; Tremor (Muscular contraction)
• ISSN: 2160-8288; 2160-8288
• DOI: 10.5334/tohm.532

A broad phenotypical spectrum including congenital cardiac and/or palatal malformations, neuropsychiatric disorders such as intellectual disability, schizophrenia, attention-deficit hyperactivity, autism spectrum, anxiety disorders, and epilepsy exists.1 The reason for this broad phenotypical variability is largely unexplained, but it could be the result of individual or multigenic reduced gene dosage and permissive variants in modifier genes elsewhere in the genome.2 Among movement disorders, Dopa-responsive parkinsonism is the most commonly reported movement disorder.2,3 Myoclonus has rarely been reported and the electrophysiological characterization is lacking.3,4 We report two 22q11.2DS patients with myoclonus of subcortical origin as the presenting movement disorder, with extensive clinical and electrophysiological analysis. Previous reports have described early-onset levodopa-responsive parkinsonism and patients with parkinsonian features without a formal diagnosis of Parkinson’s disease (PD) in 22q11.2DS.2,6 To our knowledge, only one other case with primary myoclonus in the absence of epilepsy has been reported, describing a female patient with myoclonus of head, trunk, and limbs since the age of 5.4 Other rare cases have been associated with myoclonic epilepsy, suggestive of a cortical origin, or myoclonus induced by neuroleptic treatment.3,7,8 Interestingly, the COMT gene of the catechol-O-methyltransferase enzyme, responsible for dopamine degradation, is located in the classical 22q11.2 deletion region.9,10 Elevated levels of presynaptic dopamine have previously been observed on functional neuroimaging studies in young adult patients with 22q11.2DS without a formal diagnosis of PD.11 It has been hypothesized that hyperdopaminergic autotoxicity could lead to PD.11 Whether this hyperdopaminergic autotoxicity plays a role in determining the phenotype of our patients is unclear taking into account the complex genetic disorder. E. Roze received support for research from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Laurière, and Agence Nationale de la Recherche; he has served on scientific advisory boards for Orkyn, Aguettant, Merz-Pharma; has received honoraria for speeches from Orkyn, Aguettant, Merz-Pharma, Everpharma, and International Parkinson and Movement Disorders Society; has received travel grants from Vitalair, Aguettant, Merz-Pharma, Ipsen, Merck, Orkyn, Elivie, Dystonia medical Resea