Myoclonus is a complex disorder of rapid repetitive muscle jerks that can occur in proximal or distal appendicular or axial muscles. It can be of cortical, sub-cortical or spinal cord origin; part of progressive and severely disabling epilepsy syndromes, basal ganglia conditions, and physiological or even functional (psychogenic)1.
A systematic review of the literature shows the knowledge gap of the genetic causes of myoclonus in South Africa with 25 identified publications from Africa of which eleven were from South Africa. Publications varied from case studies to case series and included four publications with cortical myoclonic tremor (CMT) and two with North Sea Progressive Myoclonic Epilepsy, two with subcortical myoclonus and case studies with rare cases of individuals with myoclonic disorders.
In this publication the study of myoclonus in three different settings is presented. In the first: cortical myoclonic tremor (CMT), a rapid distal form of myoclonus, resembling tremor, with neurophysiological evidence of cortical origin. The study researched a South African family with Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE). The first part of this study showed the median onset of cortical tremor 16 was and that of epilepsy was 42 years; patients were stable with long term follow up after 30 years without evidence of progressive ataxia or cognitive impairment. The second part of the study presents the discovery of the genetic mutation causing this condition: a pentanucleotide repeat expansion in the intronic region of the STARD7 gene. This mutation was also found in families with FCMTE2 with a similar phenotype and followed on work showing pentanucleotide repeat expansion mutations in other forms of FCMTE in different genetic locations.
The second setting proved a new mutation, a premature stop mutation p.L275X, in the epsilon-sarcoglycan gene causing subcortical origin, Myoclonus Dystonia Syndrome (MDS) in a three generation South African family with mild phenotype differences in the clinical presentation: myoclonus and dystonia in the same appendicular body part as well as truncal. Two of the affected individuals studied underwent Deep Brain Stimulation surgery of the Globus Pallidum with significant sustained improvement in the motor and non-motor features of MDS recorded and confirmed by a blinded rater.
In the third setting, two patients with sporadic Paroxysmal Non-kinesigenic dyskinesia (PNKD) with the complex phenomenology of episodic dystonia, myoclonus and chorea of South African origin is presented. Both patients underwent successful DBS of the pallidum with long-term outcomes presented. Although these two individuals were not tested for the known myofibrillogenesis regulator-1 (MR-1) mutation they represent two cases of this rare disorder from South African setting and prove the successful use of DBS treatment.