cqvip:Action myoclonus renal failure syndrome (AMRF) is a distinctive form of progr essive myoclonus epilepsy associated with renal dysfunction. The syndrome was no t recognized prior to the advent of dialysis and renal transplantation because o f its rapidly fatal course if renal failure is untreated. The first and only des cription of AMRFwas in fourFrench Canadian patients in three families (Andermann et al., 1986). We now describe 15 individuals with AMRF from five countries, in cluding a fol low up of the four French Canadian patients, allowing a more com plete characterization of this disease. Our 15 patients with AMRF belong to nine different families. Segregation analyses were compatible with autosomal recessive inheritance. In addition, our findings sho w that AMRF can present with either renal or neurological features. Tremor (onse t 17-26 years, mean 19.8 years, median 19 years) and progressively disabling ac tion myoclonus (onset 14-29 years, mean 21.7 years, median 21 years), with infr equent generalized seizures (onset 20-28 years, mean 22.7 years, median 22 year s) and cerebellar features are characteristic. Proteinuria, detected between age s 9 and 30 years in all cases, progressed to renal failure in 12 out of 15 patie nts within 0-8 years after proteinuria detection. Brain autopsy in two patients revealed extraneuronal pigment accumulation. Renal biopsies showed collapsing g lomerulopathy, a severe variant of focal glomerulosclerosis. This study extends the AMRF phenotype, and demonstrates a more extensive ethnic and geographic dist ribution of a syndrome originally believed to be confined to individuals of Fren ch Canadian ancestry. The independent progression of neurological and renal diso rders in AMRF suggests a unitary molecular lesion with pleiotropic effects. Our results demonstrate that the renal lesion in AMRF is a recessive form of collaps ing glomerulopathy. Genes identified for focal segmental glomerulosclerosis and involved with the function of the glomerular basement membrane and related prote ins are thus good candidates. Treatment can improve quality of life and extend t he lifespan of these patients. Dialysis and renal transplantation are effective for the renal but not the neurological features, which continue to progress even in the presence of normalized renal function; the latter can be managed with an ti myoclonic and anti epileptic drugs.
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