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Action myoclonus–renal failure syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Action myoclonus–renal failure syndrome

Action myoclonus–renal failure (AMRF) syndrome is a rare genetic disorder that causes involuntary muscle twitching and progressive kidney disease, typically appearing in adolescence or young adulthood.

Overview & Symptoms

Action myoclonus–renal failure (AMRF) syndrome causes episodes of involuntary muscle jerking or twitching (myoclonus) and, often, kidney (renal) disease. Although the condition name refers to kidney disease, not everyone with the condition has problems with kidney function.

The movement problems associated with AMRF syndrome typically begin with involuntary rhythmic shaking (tremor) in the fingers and hands that occurs at rest and is most noticeable when trying to make small movements, such as writing. Over time, tremors can affect other parts of the body, such as the head, torso, legs, and tongue. Eventually, the tremors worsen to become myoclonic jerks, which can be triggered by voluntary movements or the intention to move (action myoclonus). These myoclonic jerks typically occur in the torso; upper and lower limbs; and face, particularly the muscles around the mouth and the eyelids. Anxiety, excitement, stress, or extreme tiredness (fatigue) can worsen the myoclonus. Some affected individuals develop seizures, a loss of sensation and weakness in the limbs (peripheral neuropathy), or hearing loss caused by abnormalities in the inner ear (sensorineural hearing loss). Severe seizures or myoclonus can be life-threatening.

When kidney problems occur, an early sign is excess protein in the urine (proteinuria). Kidney function worsens over time, until the kidneys are no longer able to filter fluids and waste products from the body effectively (end-stage renal disease).

AMRF syndrome typically begins causing symptoms between ages 15 and 25, but it can appear at younger or older ages. The age of onset and the course of the condition vary, even among members of the same family. Either the movement problems or kidney disease can occur first, or they can begin at the same time. Most people survive 7 to 15 years after the symptoms appear.

Frequency

AMRF syndrome is a rare condition that has been found worldwide. Its exact prevalence is unknown. At least 38 individuals with the condition have been described in the medical literature.

Causes & Genetic Factors

AMRF syndrome is caused by mutations in the SCARB2 gene. This gene provides instructions for making the LIMP-2 protein, which transports an enzyme called beta-glucocerebrosidase to cellular structures called lysosomes. Lysosomes are specialized compartments that digest and recycle materials. In these compartments, beta-glucocerebrosidase breaks down a fatty substance called glucocerebroside. The LIMP-2 protein remains in the lysosome after transporting beta-glucocerebrosidase and is important for the stability of these structures.

SCARB2 gene mutations associated with AMRF syndrome lead to production of an altered LIMP-2 protein that cannot get to the lysosome. As a result, the movement of beta-glucocerebrosidase to lysosomes is impaired. It is thought that a shortage of beta-glucocerebrosidase function in these structures contributes to the signs and symptoms of AMRF syndrome, although the mechanism is unclear. Researchers are working to understand why some people with SCARB2 gene mutations have kidney problems and others do not.

Associated Genes

  • SCARB2

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Action myoclonus-renal failure syndrome
  • Action myoclonus–renal failure syndrome
  • AMRF
  • Epilepsy, progressive myoclonic 4, with or without renal failure
  • EPM4
  • Familial myoclonus with renal failure
  • Myoclonus-nephropathy syndrome
  • Progressive myoclonus epilepsy with renal failure

Frequently Asked Questions

No, kidney transplantation or dialysis treats the end-stage renal disease but does not cure or halt the neurological decline. Because the underlying SCARB2 protein deficiency affects cells throughout the central and peripheral nervous system, the action myoclonus, seizures, and sensorineural hearing loss will continue to progress independently of restored kidney function.
MRF is inherited in an autosomal recessive pattern caused by mutations in the SCARB2 gene. Both parents must be asymptomatic carriers for a child to be affected, carrying a 25 percent recurrence risk for each subsequent pregnancy. Full-gene sequencing of SCARB2 confirms the diagnosis in an affected person, after which targeted carrier testing can be offered to siblings and extended family members alongside genetic counseling.
Routine urinalysis to check for proteinuria (protein in the urine) is the most critical early screening tool, often revealing abnormalities before serum markers rise. Patients presenting with unexplained progressive action tremors or myoclonus should undergo regular urine protein-to-creatinine ratio tests, serum creatinine, and estimated glomerular filtration rate (eGFR) assessments to detect early nephrotic-range proteinuria and declining kidney clearance.
Broad-spectrum anti-seizure drugs such as levetiracetam, valproic acid, clonazepam, and brivaracetam are typically first-line choices to reduce myoclonic jerking. Conversely, classic sodium channel blockers like phenytoin, carbamazepine, and vigabatrin are generally avoided because they can paradoxically worsen myoclonus in progressive myoclonus epilepsies. Medication selection and dosing must also be continuously modified based on the patient's degree of renal impairment.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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