Abstract
Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder, typically alcohol-responsive upper body myoclonus and dystonia. The majority of autosomal dominant familial cases are caused by epsilon-sarcoglycan gene (SGCE) mutations. Previous publications have observed increased rates of psychiatric disorders amongst SGCE mutation-positive populations. We analyzed the psychiatric data from four international centers, forming the largest cohort to date, to further determine the extent and type of psychiatric disorders in M-D. Psychiatric data from SGCE mutation-positive M-D cohorts, collected by movement disorder specialists in the Netherlands, United Kingdom, United States, and Germany, were analyzed. These data were collected using standardized, systematic questionnaires allowing classification of symptoms according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Based on motor findings and SGCE mutation analysis, participants were classified into one of three groups: manifesting carriers, nonmanifesting carriers and noncarriers. Data from 307 participants were evaluated (140 males, 167 females, mean age at examination: 42.5 years). Two-thirds of motor affected mutation carriers (n = 132) had ≥1 psychiatric diagnosis, specific, and social phobias being most common followed by alcohol dependence and obsessive-compulsive disorder (OCD). Compared to familial controls, affected mutation carriers had significantly elevated overall rates of psychiatric disorders (P < 0.001). The most significant differences were observed with alcohol dependence (P < 0.001), OCD (P < 0.001), social and specific phobias (P < 0.001). M-D due to SGCE mutations is associated with specific psychiatric disorders, most commonly OCD, anxiety-related disorders, and alcohol dependence. These suggest either a potential pleiotropic function for SGCE within the central nervous system or a secondary effect of the motor disorder.
Highlights
Myoclonus-dystonia (M-D) is a rare hyperkinetic movement disorder typically characterized by myoclonus of the trunk and upper limbs in conjunction with dystonia of the neck or hands.[1,2] Onset of motor symptoms is usually in the first two decades of life and are typically alcohol responsive
A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene (SGCE), which encodes the epsilon-sarcoglycan protein.[3]
Mean age at assessment was similar across manifesting carriers (MC) and NC cohorts, while those in the nonmanifesting carriers (NMC) sub-group were, on average, 10 years older
Summary
Myoclonus-dystonia (M-D) is a rare hyperkinetic movement disorder typically characterized by myoclonus of the trunk and upper limbs in conjunction with dystonia of the neck or hands (writer’s cramp).[1,2] Onset of motor symptoms is usually in the first two decades of life and are typically alcohol responsive. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene (SGCE), which encodes the epsilon-sarcoglycan protein.[3] More than 40 different point mutations have been identified, these resulting in proteosomal degradation and failure of expression of the mutated protein at the cell-surface membrane.[4]. Psychiatric symptoms have been reported to be prevalent amongst SGCE mutation-positive cases.[5,6] Depression, anxiety disorders and obsessive-compulsive disorder (OCD)[7,8,9] have been frequently and repeatedly reported whereas other psychiatric diagnoses, for example, psychosis,[10] schizophrenia,[7] schizoaffective disorder,[11] Attention Deficit Hyperactivity Disorder (ADHD)[12], and Anorexia Nervosa[13] have been described predominantly in single case reports. Larger cohort studies have used systematic and standardized methods to compare results from SGCE mutation-positive M-D cohorts to control groups, finding OCD, in particular compulsivity,[7] and anxiety-related disorders to be the most prominent reported neuropsychiatric features.[8]
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