Myoclonus-dystonia (M-D) is a movement disorder that is often associated with mutations in epsilon-sarcoglycan (SGCE), a maternally imprinted gene at 7q21.3.
We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype.
Dystonias with known genes include DYT1 and DYT6 dystonia, presenting as isolated torsion dystonia, as well as DYT5 (dopa-responsive dystonia), DYT11 (myoclonus-dystonia), and DYT12 (rapid-onset dystonia-parkinsonism), where dystonia occurs in conjunction with other types of movement disorders.
Extensive batteries of neuropsychological tests and psychiatric questionnaires were administered to DYT11 gene mutation-carrying (MC) M-D patients (n=31), non-mutation-carrying (NMC) M-D patients (n=20) and a healthy control group (n=36).
This report presents a novel mutation in the SGCE gene causing myoclonus dystonia and extends the phenotype of myoclonus dystonia to also include alcohol-induced dystonia.
Neuroimaging studies of DYT11M-D patients show reduced dopamine D2 receptor (D2R) availability, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot beruled out.
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.
A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse ε-sarcoglycan in the late secretory pathway.
Missense mutations in the SGCE gene encoding ε-sarcoglycan account for approximately 15% of SGCE-positive cases of myoclonus-dystonia syndrome (MDS) in humans.
The development of myoclonus in this patient lends further support to the hypothesis that abnormal imprinting of the SGCE gene is responsible for some cases of myoclonus-dystonia syndrome.
The physiology and surgical response for a 63-year-old woman who underwent GPi DBS for M-D with onset at age 2 and related to a mutation in the epsilon-sarcoglycan gene (SGCE) is described.