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Action myoclonus-renal failure syndrome(AMRF; EPM4)

MedGen UID:
155629
Concept ID:
C0751779
Disease or Syndrome
Synonyms: Epilepsy, progressive myoclonic 4, with or without renal failure; EPILEPSY, PROGRESSIVE MYOCLONIC, 4, WITH RENAL FAILURE; EPILEPSY, PROGRESSIVE MYOCLONIC, 4, WITHOUT RENAL FAILURE; MYOCLONUS-NEPHROPATHY SYNDROME
SNOMED CT: AMRF - action myoclonus renal failure (764453009); Progressive myoclonic epilepsy type 4 (764453009); Myoclonus nephropathy syndrome (764453009); Action myoclonus renal failure syndrome (764453009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SCARB2 (4q21.1)
 
Monarch Initiative: MONDO:0009699
OMIM®: 254900
Orphanet: ORPHA163696

Definition

The action myoclonus-renal failure syndrome, also known as progressive myclonic epilepsy-4 with or without renal failure (EPM4), is an autosomal recessive progressive myoclonic epilepsy associated with renal failure. Cognitive function is preserved (Badhwar et al., 2004). Some patients do not develop renal failure (Dibbens et al., 2009). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/action-myoclonus-renal-failure-syndrome

Clinical features

From HPO
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Kidney disorder
MedGen UID:
9635
Concept ID:
C0022658
Disease or Syndrome
A nonspecific term referring to disease or damage of the kidneys.
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Glomerulopathy
MedGen UID:
451033
Concept ID:
C0268731
Disease or Syndrome
Inflammatory or noninflammatory diseases affecting the glomeruli of the nephron.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Action tremor
MedGen UID:
65875
Concept ID:
C0234376
Sign or Symptom
A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement.
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Normochromic anemia
MedGen UID:
66731
Concept ID:
C0235983
Finding
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Anasarca
MedGen UID:
101794
Concept ID:
C0151603
Pathologic Function
An extreme form of generalized edema with widespread and massive edema due to effusion of fluid into the extracellular space.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAction myoclonus-renal failure syndrome
Follow this link to review classifications for Action myoclonus-renal failure syndrome in Orphanet.

Professional guidelines

PubMed

Erdoğan S, Yalçın Çakmaklı G, Elibol B, Ceylaner S, Akbostancı MC
Acta Neurol Belg 2023 Dec;123(6):2441-2444. Epub 2023 Apr 29 doi: 10.1007/s13760-023-02269-z. PMID: 37119471

Recent clinical studies

Etiology

Zunke F, Andresen L, Wesseler S, Groth J, Arnold P, Rothaug M, Mazzulli JR, Krainc D, Blanz J, Saftig P, Schwake M
Proc Natl Acad Sci U S A 2016 Apr 5;113(14):3791-6. Epub 2016 Mar 21 doi: 10.1073/pnas.1514005113. PMID: 27001828Free PMC Article
Zeigler M, Meiner V, Newman JP, Steiner-Birmanns B, Bargal R, Sury V, Mengistu G, Kakhlon O, Leykin I, Argov Z, Abramsky O, Lossos A
J Neurol Sci 2014 Apr 15;339(1-2):210-3. Epub 2014 Jan 23 doi: 10.1016/j.jns.2014.01.022. PMID: 24485911
Dibbens LM, Michelucci R, Gambardella A, Andermann F, Rubboli G, Bayly MA, Joensuu T, Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, Berkovic SF
Ann Neurol 2009 Oct;66(4):532-6. doi: 10.1002/ana.21765. PMID: 19847901
Ramachandran N, Girard JM, Turnbull J, Minassian BA
Epilepsia 2009 May;50 Suppl 5:29-36. doi: 10.1111/j.1528-1167.2009.02117.x. PMID: 19469843

Diagnosis

Atasu B, Acarlı ANO, Bilgic B, Baykan B, Demir E, Ozluk Y, Turkmen A, Hauser AK, Guven G, Hanagasi H, Gurvit H, Emre M, Gasser T, Lohmann E
BMC Neurol 2022 Mar 28;22(1):122. doi: 10.1186/s12883-022-02628-y. PMID: 35346091Free PMC Article
Zeigler M, Meiner V, Newman JP, Steiner-Birmanns B, Bargal R, Sury V, Mengistu G, Kakhlon O, Leykin I, Argov Z, Abramsky O, Lossos A
J Neurol Sci 2014 Apr 15;339(1-2):210-3. Epub 2014 Jan 23 doi: 10.1016/j.jns.2014.01.022. PMID: 24485911
Gaspar P, Kallemeijn WW, Strijland A, Scheij S, Van Eijk M, Aten J, Overkleeft HS, Balreira A, Zunke F, Schwake M, Sá Miranda C, Aerts JM
J Lipid Res 2014 Jan;55(1):138-45. Epub 2013 Nov 8 doi: 10.1194/jlr.M043802. PMID: 24212238Free PMC Article
Zachos C, Blanz J, Saftig P, Schwake M
Traffic 2012 Aug;13(8):1113-23. Epub 2012 May 15 doi: 10.1111/j.1600-0854.2012.01372.x. PMID: 22537104
Dibbens LM, Michelucci R, Gambardella A, Andermann F, Rubboli G, Bayly MA, Joensuu T, Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, Berkovic SF
Ann Neurol 2009 Oct;66(4):532-6. doi: 10.1002/ana.21765. PMID: 19847901

Therapy

Mervaala E, Andermann F, Quesney LF, Krelina M
Neurology 1990 Jan;40(1):53-6. doi: 10.1212/wnl.40.1.53. PMID: 2104965
Andermann E, Andermann F, Carpenter S, Wolfe LS, Nelson R, Patry G, Boileau J
Adv Neurol 1986;43:87-103. PMID: 3946122

Prognosis

Tian WT, Liu XL, Xu YQ, Huang XJ, Zhou HY, Wang Y, Tang HD, Chen SD, Luan XH, Cao L
Seizure 2018 Apr;57:80-86. Epub 2018 Mar 14 doi: 10.1016/j.seizure.2018.03.015. PMID: 29605618
Dibbens L, Schwake M, Saftig P, Rubboli G
Epileptic Disord 2016 Sep 1;18(S2):63-72. doi: 10.1684/epd.2016.0843. PMID: 27582254
Chaves J, Beirão I, Balreira A, Gaspar P, Caiola D, Sá-Miranda MC, Lima JL
Seizure 2011 Nov;20(9):738-40. Epub 2011 Jul 22 doi: 10.1016/j.seizure.2011.06.018. PMID: 21782476
Dibbens LM, Michelucci R, Gambardella A, Andermann F, Rubboli G, Bayly MA, Joensuu T, Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, Berkovic SF
Ann Neurol 2009 Oct;66(4):532-6. doi: 10.1002/ana.21765. PMID: 19847901
Badhwar A, Berkovic SF, Dowling JP, Gonzales M, Narayanan S, Brodtmann A, Berzen L, Caviness J, Trenkwalder C, Winkelmann J, Rivest J, Lambert M, Hernandez-Cossio O, Carpenter S, Andermann F, Andermann E
Brain 2004 Oct;127(Pt 10):2173-82. Epub 2004 Sep 13 doi: 10.1093/brain/awh263. PMID: 15364701

Clinical prediction guides

Atasu B, Acarlı ANO, Bilgic B, Baykan B, Demir E, Ozluk Y, Turkmen A, Hauser AK, Guven G, Hanagasi H, Gurvit H, Emre M, Gasser T, Lohmann E
BMC Neurol 2022 Mar 28;22(1):122. doi: 10.1186/s12883-022-02628-y. PMID: 35346091Free PMC Article
Tian WT, Liu XL, Xu YQ, Huang XJ, Zhou HY, Wang Y, Tang HD, Chen SD, Luan XH, Cao L
Seizure 2018 Apr;57:80-86. Epub 2018 Mar 14 doi: 10.1016/j.seizure.2018.03.015. PMID: 29605618
Gaspar P, Kallemeijn WW, Strijland A, Scheij S, Van Eijk M, Aten J, Overkleeft HS, Balreira A, Zunke F, Schwake M, Sá Miranda C, Aerts JM
J Lipid Res 2014 Jan;55(1):138-45. Epub 2013 Nov 8 doi: 10.1194/jlr.M043802. PMID: 24212238Free PMC Article
Chaves J, Beirão I, Balreira A, Gaspar P, Caiola D, Sá-Miranda MC, Lima JL
Seizure 2011 Nov;20(9):738-40. Epub 2011 Jul 22 doi: 10.1016/j.seizure.2011.06.018. PMID: 21782476

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