Clinical Guidance
SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal involvement that can range from mild proteinuria to steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD) . In some instances, renal involvement is not observed; thus, PME without proteinuria caused by biallelic SCARB2 pathogenic variants is considered to be one end of the spectrum of SCARB2-AMRF . Of note, while all reported individuals developed neurologic findings, renal manifestations were reported to predate neurologic involvement by decades in some instances. Thus, the absence of neurologic involvement should not preclude consideration of SCARB2-AMRF in individuals with kidney disease . The age of onset varies, even within the same family. • Neurologic manifestations can appear before (in one third of affected individuals), simultaneously, or after renal manifestations. In juvenile SCARB2-AMRF, onset is usually in the late teenage years or early in the third decade . • In some persons renal manifestations occur early (late childhood or early teenage years) and neurologic involvement much later (late in the third decade or early in the fourth decade) . • In three persons of Japanese descent who did not develop SRNS, neurologic manifestations appeared in the fifth or sixth decade . See . The neurologic and renal manifestations progress independently. Of note, the neurologic manifestations are not the result of a metabolic encephalopathy due to renal involvement (chronic kidney disease [CKD] or ESKD) and are not improved by treatment of the renal disease by either dialysis or by kidney transplantation . The use of anti-rejection medications such as cyclosporine known to induce tremor can mistakenly be blamed for the emergence of myoclonus before a molecular diagnosis of SCARB2-AMRF is established. Even in the same family, the number and range of clinical manifestations and the order of their appearance can vary. Neurologic manifestations may occur first or in isolation in some family members, and renal manifestations may occur first or in isolation in other family members . Renal manifestations can be variable even within the same family, including proteinuria, reduced creatinine clearance, CKD, or ESKD. Some individuals do not develop kidney disease . The disease progresses relentlessly, with neurologic deterioration (especially increasing severity of myoclonus) and/or ESKD leading to death within seven to 15 years after onset. Table 2. SCARB2-Related Action Myoclonus – Renal Failure Syndrome: Frequency of Select Neurologic Features
