7. Clinical and EEG features of action myoclonus–renal failure syndrome

Abstract

Action myoclonus renal failure (AMRF) syndrome is an autosomal recessive form of progressive myoclonus epilepsy with tremor and myoclonus that may be intractable. It was initially described in three French Canadian families. AMRF is caused by mutations in the SCARB2 gene, encoding a lysosomal membrane protein. Disease onset is usually in the late teens or early twenties, and begins with tremor and proteinuria, progressing to action myoclonus, tonic–clonic seizures and renal failure. We describe the clinical and EEG investigations, including EEG with surface EMG electrodes (EEG-sEMG), as well as clinical video recording in three patients with AMRF syndrome associated with a confirmed SCARB2 gene mutation. Patients 1 and 2 had onset of action myoclonus at 21 and 22 years, respectively. They had no proteinuria. EEG-sEMG in both patients showed a normal background activity with numerous trains of generalized polyspike and waves at a frequency of 4 Hz, at times associated with jerks. In patient 1 there was photosensitivity at lower stimulation frequencies (2–6 Hz) and one generalized tonic–clonic seizure was recorded at 8 Hz lasting 1 min. Patient 3 presented fine tremor of upper limbs at 14 years, renal failure at 15 years, and action myoclonus at 27 years. He never had tonic–clonic seizures. The EEG-sEMG showed a tremor that had a frequency of 4–5 Hz, there were no myoclonic jerks demonstrated on surface electrodes. All three patients had normal intelligence and the SCARB2 nonsense mutation Q288X. The early clinical findings in AMRF are fine tremor and proteinuria, followed by action myoclonus, renal failure and occasional generalized tonic–clonic seizures. In some patients, the renal failure may present prior to the neurological symptoms or may not develop. The key EEG findings consist of background activity within the normal range, unlike many PME’s, where it is slow. The other EEG findings are similar to those seen in other PME’s, in particular the photosensitivity at low stimulation frequencies. In the early stages of the disease, JME should be in the differential diagnosis. If the tremor and myoclonus become intractable, and/or the patient develops proteinuria or renal failure, AMRF should be considered.