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Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

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Action Myoclonus – Renal Failure Syndrome

, MD, , MD, FRCP(C), and , MDCM, PhD, FCCMG.

Author Information and Affiliations

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Estimated reading time: 36 minutes

Summary

Clinical description.

Action myoclonus – renal failure (AMRF) syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal failure; however, in some instances, the kidneys are not involved. Neurologic manifestations can appear before, simultaneously, or after the renal manifestations. Disease manifestations are usually evident in the late teens or early twenties. In the rare instances in which renal manifestations precede neurologic findings, onset is usually in late childhood / early adolescence but can range to the fifth or sixth decade. Neurologic manifestations begin with tremor at rest (which is exacerbated by fine motor activities) and progress to involuntary, action-activated myoclonic jerks that involve bulbar, proximal, and distal limb muscles; involuntary spontaneous myoclonic jerks; and generalized clonic-tonic-clonic seizures. Sensorimotor peripheral neuropathy and sensorineural hearing loss can also be observed. Renal manifestations include proteinuria that can progress to nephrotic syndrome and end-stage renal disease.

Diagnosis/testing.

The diagnosis of AMRF syndrome is suspected in a previously healthy teenager or young adult with the characteristic neurologic and/or renal manifestations. The diagnosis is confirmed in individuals with biallelic (homozygous or compound heterozygous) loss-of-function pathogenic variants in SCARB2.

Management.

Treatment of manifestations: Symptomatic pharmacologic and psychosocial support is the mainstay of care for the neurologic manifestations. Response to treatment is variable and may worsen over time, necessitating rehabilitative management. Renal insufficiency requires dialysis but response to treatment is poor, and renal transplantation is often necessary.

Prevention of secondary complications: Standard measures for prevention of aspiration pneumonia and sudden unexpected death in epilepsy should be followed.

Surveillance: Lifelong follow up should include regular monitoring of anti-seizure drug treatment and renal function (including urinary protein excretion, creatinine clearance, and estimated glomerular filtration rate) and periodic assessment of hearing and peripheral nerves.

Agents/circumstances to avoid: Diphenylhydantoin, carbamazepine, oxcarbazepine, and possibly lamotrigine increase myoclonus and should be avoided in any individual with PME.

Pregnancy management: Because some anti-seizure medications can lead to an increased risk of malformations, growth retardation, or neurodevelopmental disabilities in exposed fetuses, standard measures for prevention of fetopathy should be followed.

Genetic counseling.

AMRF syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the SCARB2 pathogenic variants in the family have been identified.

Diagnosis

Suggestive Findings

Action myoclonus – renal failure (AMRF) syndrome should be suspected in a previously healthy teenager or young adult with the following neurologic and renal manifestations [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006, Andermann 2011]:

Neurologic manifestations

  • A fine tremor of the fingers and hands, present at rest, exacerbated by fine motor activities such as writing and relieved by alcohol or propranolol, is commonly the first finding. The tremor can later involve the head, trunk, lower extremities, and sometimes tongue and voice. In the later stages of the disease, it becomes masked by striking myoclonic jerks.
  • Involuntary, action-activated myoclonic jerks, also induced by attempted and executed speech, involve bulbar as well as proximal and distal limb muscles. The myoclonus is reflex-sensitive to touch on the distal extremities.
  • Involuntary spontaneous myoclonic jerks of the face (particularly perioral) as well as synchronous and asynchronous jerks of the trunk and limbs also occur at rest.
  • Generalized clonic-tonic-clonic seizures, diurnal and/or nocturnal, start with a generalized clonic phase with preserved consciousness and proceed to unconsciousness with tonic-clonic features and urinary incontinence.
  • Other findings can include sensorimotor peripheral neuropathy (most often predominantly demyelinating or more rarely axonal) and sensorineural hearing loss (SNHL).

Renal manifestations

  • Proteinuria, the first manifestation of renal disease, is initially mild and asymptomatic.
  • Renal disease can progress to nephrotic syndrome and end-stage renal disease.
  • In some families, renal manifestations (eventually requiring renal transplantation) appear first in late childhood or early teens and neurologic manifestations in the late twenties or early thirties [Badhwar et al 2004].
  • Histologic changes include interstitial fibrosis, atrophy, focal sclerosing glomerulonephritis sometimes with features of collapsing glomerulopathy (a severe variant of glomerulosclerosis), or membranous nephropathy. No storage was observed [Andermann et al 1986, Badhwar et al 2004, Berkovic et al 2008].
  • Note: Immunostaining can show IgM and complement present in the glomerular loops and in the mesangium [Andermann et al 1986]. In one patient, a C1q nephropathy has been shown by immunohistochemistry [Balreira et al 2008, Chaves et al 2011], indicating an immune complex-mediated glomerular disease. In this patient, extensive tubular abnormalities were also present, as well as granular material in cortical tubules. No Gaucher cells were observed.

A classification that takes into account the age at disease onset and the clinical manifestations has been proposed (Table 2).

Establishing the Diagnosis

The diagnosis of action myoclonus – renal failure (AMRF) syndrome is confirmed in individuals with biallelic (homozygous or compound heterozygous) loss-of-function pathogenic variants in SCARB2 [Balreira et al 2008, Berkovic et al 2008] (Table 1).

Note: Molecular diagnosis performed early in the disease course may eliminate the need for numerous invasive neurologic and renal investigations.

Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing.

Single-gene testing

A multigene panel for progressive myoclonic epilepsy (PME) or epilepsy that includes SCARB2 and other genes of interest (see Differential Diagnosis) may also be used. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes SCARB2) fails to confirm a diagnosis in an individual with features of action myoclonus – renal failure syndrome. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene that results in a similar clinical presentation.

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Action Myoclonus – Renal Failure Syndrome

Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
SCARB2 Sequence analysis 3Estimated from Table 4: 97.5% 4
Targeted analysis of pathogenic variantsSee footnote 5.
Gene-targeted deletion/duplication analysis 6None reported
1.
2.

See Molecular Genetics for information on allelic variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

About 20 pathogenic variants have been reported to date (see Tables 3 and 4). About 2.5% of affected individuals are compound heterozygotes with an identified intragenic pathogenic variant in one allele and an unidentified variant in the other.

5.

Testing for the pathogenic variants c.862C>T (see also Table 4) (exon 7) and c.1187+3insT (see also Table 4) (intron 9) in persons of French-Canadian origin. In this population, the vast majority of probands are homozygous for c.862C>T, whereas a small proportion are compound heterozygotes for both pathogenic variants [Dibbens et al 2011].

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions and duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Clinical Characteristics

Clinical Description

Action myoclonus – renal failure (AMRF) syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal failure (Table 2); however, in some instances, renal failure is not observed. Thus, progressive myoclonus epilepsy without renal failure caused by biallelic SCARB2 pathogenic variants is considered to be one end of the spectrum of AMRF [Badhwar et al 2004, Dibbens et al 2009, Rubboli et al 2011, Guerrero-López et al 2012, Zeigler et al 2014].

The age of onset varies, even within the same family.

  • Neurologic manifestations can appear before (in 1/3 of the cases), simultaneously, or after the renal manifestations. In juvenile AMRF onset is usually in the late teens or early twenties [Andermann et al 1986, Badhwar et al 2004].
  • In some persons renal manifestations occur early (late childhood or early teens) and neurologic involvement much later (late 20s or early 30s) [Badhwar et al 2004, Hopfner et al 2011].
  • In three persons of Japanese heritage who did not develop renal failure, neurologic manifestations appeared in the fifth or sixth decade [Higashiyama et al 2013, Fu et al 2014].

The neurologic and renal manifestations progress independently. Of note, the neurologic manifestations are not the result of a metabolic encephalopathy due to renal failure and are not improved by dialysis or by renal transplantation [Andermann et al 1986, Badhwar et al 2004].

Even in the same family, the number and order of appearance of the clinical manifestations can vary. Neurologic manifestations may occur first or in isolation in some family members and renal manifestations may be first or isolated in other family members [Badhwar et al 2004]. In some families, all affected individuals have neurologic manifestations and none develop renal failure [Dibbens et al 2009, Rubboli et al 2011, Guerrero-López et al 2012, Fu et al 2014, Perandones et al 2014, Zeigler et al 2014]; however, some affected family members have proteinuria [Dibbens et al 2009, Guerrero-López et al 2012] or reduced creatinine clearance [Zeigler et al 2014].

The disease progresses relentlessly with neurologic deterioration (especially increasing severity of myoclonus) and renal failure leading to death within seven to 15 years after onset.

Table 2.

Clinical Manifestations of AMRF

Disease OnsetMajor ManifestationsCNS InvolvementRenal DiseaseOther Possible Manifestations
Juvenile PME and RF
  • Tremor
  • Progressive action myoclonus
  • Myoclonus at rest
  • Ataxia, dysarthria
  • Severe epileptic photosensitivity
  • GTCS (rare at onset; relatively infrequent even in later stages)
  • Proteinuria (progressing from mild to severe)
  • Segmental GP and/or TP
  • Renal failure
  • PNP
  • SNHL
  • DCM
PME
  • Tremor
  • Progressive action myoclonus
  • Myoclonus at rest
  • Ataxia, dysarthria
  • Severe epileptic photosensitivity
  • GTCS (infrequent at onset)
  • Mild proteinuria
  • Mild decrease of creatinine clearance
  • PNP
  • Mild generalized muscle atrophy w/out fasciculations
RFNeurologic manifestations as listed above may develop late in disease course.
  • May begin in early childhood or early teens
  • Proteinuria, progressive
  • Segmental GP
  • TP
  • Renal failure
LatePME
  • Tremor
  • Ataxia, dysarthria
  • Progressive action myoclonus
  • GTCS may occur infrequently
  • Cognitive decline
None reported

DCM = dilated cardiomyopathy; GP = glomerulopathy; GTCS = generalized tonic-clonic seizures; PME = progressive myoclonus epilepsy; PNP = peripheral neuropathy; RF = renal failure; SNHL = sensorineural hearing loss; TP = tubulopathy

Neurologic Disease

Fine tremor. The disease begins with bilateral fine tremor of the fingers that is noted at rest and increased by delicate movement such as writing, by intention of movement, and by maintaining an attitude in horizontal extension [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006]. The tremor can be relieved by alcohol [Andermann et al 1986, Andermann 2011, Guerrero-López et al 2012]. It becomes progressively worse until it is masked by myoclonic jerks [Badhwar et al 2004, Vadlamudi et al 2006].

Action myoclonus. The fine tremor is followed by jerking movements first of the upper and then of the lower extremities. Referred to as action myoclonus, these jerking movements are typically triggered by movements or intended movements. They are asynchronous and of variable severity.

With time, myoclonic jerks involve the proximal limbs; their amplitude and number increases by movements of the limbs, typically by walking down stairs. Action myoclonus can also involve the trunk. Attempts at speaking and executed speech can induce myoclonus of the bulbar musculature, contributing to the dysarthria. There is no palatal myoclonus.

Action myoclonus, which is also reflex-sensitive to touch over the distal extremities, can be exacerbated by anxiety, excitement, stress, and fatigue [Badhwar et al 2004, Zeigler et al 2014] and by auditory stimuli [Perandones et al 2012]. Some patients exhibit occasional myoclonus in response to startle [Badhwar et al 2004]. Of note, myoclonic jerks were significantly less frequent during pregnancy in one patient [Amrom et al 2017].

Action myoclonus represents the most disabling manifestation: it prevents affected individuals from being able to feed themselves and, thus, they become malnourished unless they receive assistance with feeding or are fed by artificial means. In the final stages, they may become bedridden or wheelchair bound. Swallowing difficulties can lead to aspiration pneumonia and death [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006].

Myoclonus at rest. Subtle myoclonic movements of the eyelids, jaws, and perioral musculature appear at rest and while speaking. Ocular dysmetria can occur later in the disease course.

Clonic-tonic-clonic seizures, which can be diurnal or nocturnal, begin with generalized clonic jerking with preserved consciousness and proceed to unconsciousness with tonic-clonic features. They occur infrequently, starting with one per annum initially [Badhwar et al 2004]. TV viewing or other light stimulation may trigger generalized myoclonic seizures or tonic-clonic seizures [Rubboli et al 2011]. Photosensitivity can become so severe that affected individuals choose to live in almost complete darkness [Rubboli et al 2011].

Ataxia and dysarthria, common findings, can be distinguished from myoclonic jerks by the presence of the cerebellar abnormalities of pendular reflexes, abnormal rebound, and hypermetric ocular saccades.

Progressive myoclonus ataxia. Some patients develop significant progressive ataxia before or after the appearance of myoclonus and, thus, have been reported to have "progressive myoclonus ataxia."

A woman age 29 years had a history of clumsiness in the lower limbs, mild gait instability, and difficulties in riding a bicycle beginning at age 21 years, two years before the onset of progressive myoclonus at age 23 years. Renal failure was evident at age 25 years, and bilateral severe SNHL was diagnosed at age 27 years [Perandones et al 2012, Perandones et al 2014].

A woman age 22 years developed postural hand tremor exacerbated by fine voluntary movements and stress. The tremor slowly worsened with multifocal spontaneous and stimulus-sensitive myoclonic jerks. No other seizures were reported, and the EEG did not show any epileptic activity (of note, the patient was taking several anti-seizure medications). Ataxia was first reported when she was wheelchair bound at age 27 years. The co-occurrence of tremor, myoclonus, and ataxia in the same patient – without generalized tonic-clonic seizures – increases the complexity of the clinical picture of this disorder [Guerrero-López et al 2012].

Peripheral neuropathy. In some families, a sensorimotor peripheral neuropathy (most often predominantly demyelinating or more rarely axonal) may be present.

Some affected individuals may be diagnosed with a predominantly demyelinating peripheral neuropathy before the onset of renal failure [Badhwar et al 2004, Costello et al 2009, Dibbens et al 2011, Hopfner et al 2011]. In the German Family I reported by Badhwar et al [2004], one family member with AMRF who was asymptomatic for polyneuropathy was initially found to have a predominantly axonal neuropathy by nerve conduction studies; several years later, he and his two affected sibs were reported to have predominantly demyelinating polyneuropathy [Hopfner et al 2011].

Mild generalized muscle atrophy was observed in one individual who exhibited mild generalized reduced tone and no fasciculations [Zeigler et al 2014].

Renal Disease

Mild proteinuria may progress to nephrotic syndrome and ultimately to renal failure (Table 2).

Dialysis and renal transplantation can prolong survival, but do not improve the neurologic features.

Mental Status

Cognitive function. Unlike individuals with most other types of progressive myoclonus epilepsy, the majority of individuals with AMRF syndrome remain mentally alert. However, dementia has been documented in two unrelated individuals of Japanese ancestry, one with the juvenile-onset form, and the other with the late-onset form, who have different SCARB2 pathogenic variants [Fu et al 2014].

Psychological complications. Individuals with AMRF may exhibit somatic concerns or depressed mood, or may in exceptional cases commit suicide [Amrom et al 2017].

Other Findings

Cardiac disease. In a German family, echocardiography revealed dilated cardiomyopathy in two of three affected sibs at ages 14 and 21 years [Hopfner et al 2011]. In addition, these sibs had sensorimotor peripheral neuropathy.

Hearing loss / deafness. Frank or subclinical sensorineural hearing loss (SNHL) can be part of the spectrum of AMRF syndrome. Three individuals with AMRF had adult-onset SNHL, which was mild in one individual from one family [Rubboli et al 2011] and severe and asymmetric in an individual from a second family [Perandones et al 2012], in which a sister had preclinical hearing loss [Perandones et al 2014].

Thus in the same family, the SNHL can be severe or subclinical or absent [Badhwar et al 2004, Perandones et al 2012, Perandones et al 2014].

Common causes of death in AMRF. Sudden death may occur during or after a generalized epileptic seizure due to aspiration, severe myoclonus and unmanageable saliva, or an undetermined cause. Death can also occur due to aspiration pneumonia, renal failure, or rejection of a renal transplant [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006, Rubboli et al 2011].

Late-Onset AMRF

Disease onset in the fifth or sixth decade has been reported in two Japanese families.

Higashiyama et al [2013] reported one family with two sibs with AMRF without renal failure. The sister presented with myoclonic jerks at age 43 years; her older brother presented with gait difficulties at age 52 years. Both were homozygous for the SCARB2 pathogenic variant c.1385_1390del6insATGCATGCACC.

Fu et al [2014] reported single affected individuals from two other Japanese families, one of whom (Patient 1) had late-onset disease. Patient 1 presented with onset of difficulties going up and down the stairs at age 45 years. Of note, he was homozygous for the same pathogenic variant as the two sibs reported by Higashiyama et al [2013]. Although the two families with the late-onset form are likely related as they originate from the same rural area, the precise relationship is unknown [Hiroshi Doi, 2014, personal communication; Hitoshi Takahashi, June 2014, personal communication]. Of note, Patient 2 reported by Fu et al [2014] presented at age 20 years, was unrelated to Patient 1, and was homozygous for a different SCARB2 pathogenic variant.

Specialized Studies

EEG findings [Andermann et al 1986, Badhwar et al 2004]. Background activity may be normal in some patients or show diffuse slowing at 6.5 to 7.5 Hz. Relatively low-voltage spike and spike-wave discharges, rather infrequent, bilaterally synchronous and generalized or confined to the central vertex or both occipital regions, increased by hyperventilation and intermittent photic stimulation, may be present.

Some of the brief spike potentials are difficult to distinguish from muscle potentials except that they are seen at the vertex where there is no muscle artifact. The electromyogram myoclonic potentials are sometimes associated with cerebral potentials and at other times occur independently, suggesting a subcortical origin with a secondary corticoreticular generalization.

Intermittent photic stimulation may produce whole-body myoclonus with multiple spikes in the EEG record associated with slow waves [Andermann et al 1986]. These generalized spike-polyspike-wave bursts can outlast the duration of light stimulation [Rubboli et al 2011].

Myoclonic seizures can be triggered by eye closure and resolve by eye opening [Rubboli et al 2011].

Overnight sleep recording can show fast spikes over the vertex spreading to bilateral frontocentral regions during rapid eye movement (REM) sleep.

Follow up over the course of the disease shows a preserved alpha background activity at disease onset, with rare generalized or focal epileptiform discharges. Over the years, irregular slower theta and delta waves progressively intermix with the alpha waves, and the epileptic activity becomes more frequent [Rubboli et al 2011].

MRI findings. Brain MRI may be normal or show mild diffuse cerebral and cerebellar atrophy [Andermann et al 1986, Badhwar et al 2004, Perandones et al 2012].

Electromyography findings. Nerve conduction analysis can show slowed nerve conduction velocities and prolonged F-waves, consistent with a mixed, mainly demyelinating polyneuropathy [Dibbens et al 2011, Hopfner et al 2011, Rubboli et al 2011].

In one patient, concentric needle electromyography (EMG) was suggestive of chronic anterior horn involvement [Zeigler et al 2014].

Brain histologic findings. A constant and pathognomonic finding is the presence of small and large autofluorescent pigment granules up to 10 µm in size in astrocytes and in certain cells in the meninges. The pigment granules are more prominent in laminae I and II of the cerebral cortex, the globus pallidus and putamen, and the Bergmann astrocytes in the cerebellar cortex; they are not seen in the thalamus, brain stem nuclei, dentate nuclei of the cerebellum, or spinal cord gray matter. The granules are both separate from as well as adjacent to glial cell nuclei, suggesting that at least some were within astrocytes [Andermann et al 1986, Badhwar et al 2004, Berkovic et al 2008].

Neurons contain normal amounts of lipofuscin and no pigment granules [Andermann et al 1986, Badhwar et al 2004]. In two affected individuals of Japanese ancestry extraneuronal brown pigment deposition, exclusively in astrocytic cytoplasm and surrounded by a membrane, was widely scattered throughout the brain [Fu et al 2014].

Click here for information about specialized studies for biologic and histologic findings.

Genotype-Phenotype Correlations

No clear genotype-phenotype correlation is evident.

Disease severity may vary among affected individuals within a family who have the same pathogenic variants. In some affected individuals, phenotypic variability may be explained by the presence of an additional pathogenic variant in another epilepsy-related gene [He et al 2014].

Nomenclature

Action myoclonus – renal failure (AMRF) syndrome has been referred to as:

  • Familial myoclonus with renal failure
  • Progressive myoclonus epilepsy with renal failure
  • Epilepsy, progressive myoclonic 4, with or without renal failure, EPM4. However, the presence or absence of renal failure represents only part of the clinical spectrum of AMRF.

The term progressive myoclonus epilepsy (PME) covers a large group of diseases characterized by myoclonus, epilepsy, and progressive neurologic deterioration.

Prevalence

Exact prevalence figures are not available. To the authors' knowledge, 38 affected individuals from 26 families have been reported to date.

AMRF was first reported in several French-Canadian families [Andermann et al 1986]; it occurs worldwide, including Europe; North, Central and South America; Australia; Asia; and the Middle East.

Families without renal failure have been reported in Italy [Dibbens et al 2009], Spain [Guerrero-López et al 2012], Asia [Higashiyama et al 2013, Fu et al 2014, He et al 2014], and the Middle East [Zeigler et al 2014].

Differential Diagnosis

At the onset of the disease, three non-progressive conditions should be considered in the differential diagnosis:

In individuals with a PME phenotype who do not have biallelic SCARB2 pathogenic variants, the following disorders should be considered:

  • Unverricht-Lundborg disease (EPM1), also referred to as EPM1A, is a progressive myoclonus epilepsy syndrome with an earlier age of onset and a slower rate of disease progression than AMRF; cognition is normal or mildly reduced [Kälviäinen et al 2008, Genton 2010]. Inheritance is autosomal recessive; biallelic pathogenic variants in CSTB (encoding cystatin B) are causative.
  • PRICKLE1-related progressive myoclonus epilepsy with ataxia (EPM1B) is a progressive myoclonus epilepsy-ataxia syndrome that presents in childhood. Ataxia begins at ages 4 to 5 years and evolves to PME with ataxia and mild or no cognitive decline. Impaired upward gaze has been observed in several affected individuals [Berkovic et al 2005, Bassuk et al 2008]. PRICKLE1-related PME with ataxia is inherited in an autosomal recessive manner.
  • Progressive myoclonus epilepsy, Lafora type is considered in individuals with visual hallucinations (occipital epilepsy) and cognitive decline. Skin biopsy shows pathognomonic Lafora bodies [Carpenter et al 1974, Carpenter & Karpati 1981]. Inheritance is autosomal recessive. Biallelic pathogenic variants in either EPM2A or NHLRC1 (EPM2B) are causative [Minassian et al 1998, Chan et al 2003].
  • EPM5 (OMIM 613832) is characterized by myoclonic seizures, cerebellar signs and deterioration of cognition as well as visual impairment [Bird and Shaw 1978]. Some phenotypic findings may be similar to dentatorubral-pallidoluysian atrophy (DRPLA) [Bird & Shaw 1978, Tsuji 2012]. Inheritance is autosomal dominant; heterozygous pathogenic variants in PRICKLE2 are causative [Tao et al 2011].
  • Progressive myoclonic epilepsy and ataxia due to KCNC1 channel mutation B (MEAK) is clinically similar to Unverricht-Lundborg disease. Inheritance is autosomal dominant; a recurrent de novo KCNC1 pathogenic variant, c.959G>A (p.Arg320His) which causes loss of function of KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, is causative [Muona et al 2015].
  • Neuronal ceroid-lipofuscinoses (NCL). In adult NCL (ANCL) (formerly called Kufs disease), initial signs and symptoms usually appear around age 30 years (range: teens to >50 years), with death occurring about ten years later. ANCL is clinically and genetically heterogeneous, and is inherited in either an autosomal dominant or autosomal recessive manner. It is distinguished from most other forms of NCL by preserved vision. The two major ANCL phenotypes are type A (the major form) and type B [Berkovic et al 1988].
    Note: ANCL type B is not part of the differential diagnosis of AMRF since it is characterized by behavioral abnormalities and dementia which may be associated with motor dysfunction, ataxia, extrapyramidal signs, and suprabulbar (brain stem) signs [Berkovic et al 1988, Smith et al 2013].
    ANCL type A is characterized by progressive myoclonic epilepsy with cognitive deterioration, ataxia, and late-occurring pyramidal and extrapyramidal signs. It can be inherited in either an autosomal dominant or autosomal recessive manner. The autosomal dominant forms have intraneuronal granular osmiophilic deposits (GRODs) observed on electron microscopy [Burneo et al 2003, Nijssen et al 2003]. Some autosomal dominant forms are caused by heterozygous pathogenic variants in DNAJC5 [Nosková et al 2011, Cadieux-Dion et al 2013, Cadieux-Dion et al 2014]. The autosomal recessive form is mainly caused by biallelic pathogenic variants in CLN6 [Arsov et al 2011].
    Other forms of ANCL type A, associated with visual loss, can result from biallelic pathogenic variants in CLN1 [van Diggelen et al 2001, Ramadan et al 2007], CLN5 [Sleat et al 2009, Xin et al 2010] or GRN [Smith et al 2012]. Inheritance is autosomal recessive.
    A juvenile form of NCL with autosomal recessive inheritance and GROD is associated with pathogenic variants in the gene encoding palmitoyl-protein thioesterase (PPT), which are also seen in the infantile form of NCL (CLN1) [Mitchison et al 1998].
  • Sialidosis type 1 (OMIM 256550) is characterized by PME with cognitive decline and can be assessed with neuroophthalmologic examination, including electroretinography [Boustany 2013, Mink et al 2013]. Sialidosis type 1 is inherited in an autosomal recessive manner and caused by biallelic pathogenic variants of NEU1 [Bonten et al 2000].
  • MERRF (myoclonic epilepsy with ragged red fibers) is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. In individuals with MERRF, blood and cerebrospinal fluid concentrations of lactate and pyruvate are commonly elevated at rest and increase excessively after moderate activity [Bindoff & Engelsen 2012, Finsterer & Zarrouk Mahjoub 2012]. MERRF is caused by pathogenic variants in mtDNA and is transmitted by maternal inheritance
  • Gaucher disease type 3, characterized by the presence of primary neurologic disease, may have onset before age two years, but often has a more slowly progressive course, with survival into the third or fourth decade. Saccade initiation failure is a common and early manifestation – suggestive of early dysfunction of supranuclear ocular motor control – and can be detected during induced optokinetic or vestibular nystagmus [Harris et al 1999]. Gaucher disease is inherited in an autosomal recessive manner and is caused by biallelic pathogenic variants in GBA (encoding the enzyme β-glucocerebrosidase) [Tsuji et al 1987, Dahl et al 1988].
  • Familial encephalopathy with neuroserpin inclusion bodies (FENIB) (OMIM 604218). Age of onset and clinical manifestations vary considerably. The spectrum of clinical phenotypes ranges from cognitive decline/dementia, dysarthria, and tremors to various forms of refractory epilepsy including progressive myoclonus epilepsy (PME) and focal or generalized seizures. Inheritance is autosomal dominant; heterozygous pathogenic variants in SERPINI1 are causative [Hagen et al 2011].
  • DRPLA (dentatorubral-pallidoluysian atrophy). Individuals with juvenile onset (age <20 years) of DRPLA present with PME and associated progressive cognitive deterioration and behavioral changes; whereas those with adult onset (age >20 years) of DRPLA present with ataxia, choreoathetosis, and dementia. DRPLA is relatively more common among the Japanese than in other ethnic populations [Takano et al 1998]. DRPLA is inherited in an autosomal dominant manner and expansion of a CAG trinucleotide/polyglutamine tract in ATN1 is causative [Tsuji 2012].

See Epilepsy, progressive myoclonic: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.

Charcot-Marie-Tooth neuropathy with focal segmental glomerulonephritis (OMIM 614455) should be considered in persons with peripheral neuropathy and glomerulonephritis [Boyer et al 2011]. Inheritance is autosomal dominant; heterozygous pathogenic variants in INF2 are causative.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with action myoclonus – renal failure (AMRF) syndrome, the following evaluations are recommended:

  • Clinical evaluation including cognitive function and school performance, emotional features, eye movements, coordination, handwriting, walking
  • Examination of myoclonus including evaluation at rest, with action, and in response to stimuli
  • EEG evaluation including photosensitivity before therapy is initiated, as it is most characteristic before the use of anticonvulsant medication
  • Renal function
  • Audiogram and brain stem auditory evoked potentials (BAEPs) to assess the possibility of clinical or subclinical sensorineural hearing loss [Rubboli et al 2011, Perandones et al 2012, Perandones et al 2014]
  • Nerve conduction velocities (NCV) and needle electromyography (EMG)
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Neurologic manifestations. Symptomatic pharmacologic and psychosocial support is the mainstay of care for the neurologic manifestations. Response to treatment is variable and may deteriorate over time, necessitating rehabilitative management.

  • Valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures.
  • Clonazepam may be used as add-on therapy for the treatment of myoclonic seizures.
  • Levetiracetam appearss to be effective for both myoclonus and generalized seizures, and is recommended in women of child bearing age.
    Note: Lamotrigine is not effective in controlling the myoclonus, and may aggravate myoclonus in some patients [Guerrini et al 1998].

Renal manifestations. Renal insufficiency requires dialysis but response to treatment is poor, and renal transplantation is often necessary.

Prevention of Secondary Complications

Standard measures for prevention of aspiration pneumonia and sudden unexpected death in epilepsy (SUDEP) should be followed; offering psychosocial support may be helpful.

Surveillance

Lifelong clinical follow up should include the following:

  • Neurologic
    • Monitoring of anti-seizure medication treatment (drug levels and clinical assessment of biological effects);
    • Periodic assessment of hearing by audiograms and BAEPs and of the peripheral nerves by NCV and needle EMG.
  • Renal function monitoring by measurement of: blood pressure; body weight; serum concentrations of creatinine, albumin, and cholesterol; 24-hour urinary protein; and creatinine clearance

Agents/Circumstances to Avoid

Diphenylhydantoin, carbamazepine, oxcarbazepine, and possibly lamotrigine increase myoclonus and should be avoided in any individual with progressive myoclonic epilepsy (PME), including AMRF.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Some anti-seizure medications can lead to an increased risk of malformations, growth retardation, or neurodevelopmental disabilities in exposed fetuses. However, when pregnant women experience prolonged seizures during pregnancy, the risk of adverse fetal outcomes is increased. Therefore, it is recommended that women with a known seizure disorder continue to take anti-seizure medication during pregnancy. Standard measures for prevention of fetopathy should be followed. These include:

  • Possible changes of medication prior to pregnancy;
  • Spacing of the anti-seizure medication into four doses a day or taking extended release medications, so that the drug levels do not have significant peaks or troughs;
  • Monitoring the dosages and drug levels of anti-seizure medication during pregnancy and after the delivery.

In addition, folic acid should be prescribed at 1 mg/day for all women of childbearing age and increased to 5 mg/day when planning a pregnancy (ideally 3 months prior to conception) and during the pregnancy, in order to prevent possible neural tube defects and other congenital malformations that can be associated with fetal exposure to anti-seizure medication.

Therapies Under Investigation

A trial of enzyme replacement therapy (ERP) with imiglucerase (60 U/kg every two weeks) in two sibs with AMRF for a period of one year did not improve the clinical status. Substrate reduction therapy (SRT) with miglustat (600 mg daily) administered to one of the two sibs resulted in a significant reduction of myoclonus [Chaves et al 2011].

Search Clinical Trials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Action myoclonus - renal failure (AMRF) syndrome is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected individual are obligate heterozygotes (i.e., carriers of one SCARB2 pathogenic variant).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

  • The offspring of an individual with action myoclonus-renal failure syndrome are obligate heterozygotes (carriers) for a SCARB2 pathogenic variant.
  • If the reproductive partner of an affected individual is a carrier of an SCARB2 pathogenic variant, the offspring have a 50% chance of being affected and a 50% chance of being a carrier.

Other family members. Each sib of the proband's parents is at 50% risk of being a carrier.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the SCARB2 pathogenic variants in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

Prenatal Testing and Preimplantation Genetic Testing

Once the SCARB2 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for AMRF are possible.

Fetal ultrasound examination. Prenatal testing by level 2 ultrasound examination does NOT detect AMRF, as disease onset is usually in the late teens or early twenties.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • American Epilepsy Society
  • Canadian Epilepsy Alliance
    Canada
    Phone: 1-866-EPILEPSY (1-866-374-5377)
  • Citizens United for Research in Epilepsy (CURE)
  • EpiCARE: a European Reference Network for rare and complex epilepsies
  • Epilepsy Foundation
    Phone: 800-332-1000; 301-459-3700
    Email: ContactUs@efa.org
  • American Kidney Fund
    Phone: 800-638-8299
  • European Rare Kidney Disease Reference Network (ERKNet)
    Phone: 49 0 6221 56-34191
    Email: contact@erknet.org
  • Kidney Foundation
    Canada
    Phone: 514-369-4806; 800-361-7494
    Email: info@kidney.ca
  • NephCure Kidney International
    Phone: 866-NephCure; 866-637-4287
    Email: info@nephcure.org
  • Nephrotic Syndrome Study Network (NEPTUNE)
    As a research consortium of physician scientists at 26 sites in the United States and Canada, along with patient advocacy groups NephCure Kidney International and the Halpin Foundation, NEPTUNE strives to bring the latest advances in research to patients diagnosed with Focal Segmental Glomerulosclerosis (FSGS), Minimal Changes Disease (MCD), and Membranous Nephropathy (MN) with an overarching goal of utilizing precision medicine for rare diseases.
    Phone: 734-615-5020
    Email: NEPTUNE-STUDY@umich.edu
  • PodoNet Registry
    The PodoNet Registry explores the demographics, causes and prognosis of patients with congenital and steroid resistant nephrotic syndrome.
    Clinical, Genetic and Experimental Research into Hereditary Disease of the Podocyte

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Action Myoclonus - Renal Failure Syndrome: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
SCARB2 4q21​.1 Lysosome membrane protein 2 SCARB2 database SCARB2 SCARB2

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Action Myoclonus - Renal Failure Syndrome (View All in OMIM)

254900EPILEPSY, PROGRESSIVE MYOCLONIC, 4, WITH OR WITHOUT RENAL FAILURE; EPM4
602257SCAVENGER RECEPTOR CLASS B, MEMBER 2; SCARB2

Gene structure. SCARB2 contains 5.5 kb with 12 exons and codes for two transcript variants; the longer variant is NM_005506.3. For a detailed summary of gene and protein information, see Table A, Gene.

Benign variants. A few sequence alterations that are not believed to have a primary role in disease causation have been found in unaffected individuals [Dibbens et al, unpublished data]. The extent to which these variants may influence the phenotype or clinical disease expression remains to be established.

Pathogenic variants. Known pathogenic variants include nonsense, missense, deletion, frameshift, and splice site variants, leading to retention of SCARB2 protein (previously known as LIMP-2) in the endoplasmic reticulum, but differentially affecting the binding to β-glucocerebrosidase (β-GC) [Blanz et al 2010]. To the authors' knowledge, all pathogenic variants identified to date are loss-of-function variants.

See Table 3 and Table 4 (pdf).

Table 3.

SCARB2 Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.862C>Tp.Gln288Ter NM_005506​.3
NP_005497​.1
c.1187+3insT

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Variants included are found in persons of French-Canadian origin; see Table 1, footnote 5.

Normal gene product. The protein encoded by SCARB2 (scavenger receptor class B, member 2) is a glycosylated 478-residue type III transmembrane protein that belongs to the CD36 family of scavenger receptors and is found in all cell types.

SCARB2 (previously known as LIMP-2) has two known physiologic functions related to lysosome biology:

  • First, it is a major lysosomal integral membrane protein playing an important role in the biogenesis and maintenance of endosomes/lysosomes and interaction with the vesicle fission/fusion machinery [Eskelinen et al 2003].
  • Second, it is a specific trafficking receptor of β-glucocerebrosidase (β-GC), the enzyme deficient in Gaucher disease [Reczek et al 2007]. It binds β-GC for transfer from the endoplasmic reticulum to the lysosome in a mannose-6-phosphate independent manner. The released β-GC remains in the endosome/lysosome whereas SCARB-2 then integrates in the limiting membrane of lysosomes, and is therefore also known as lysosomal integral membrane protein type 2 or LIMP-2 [Reczek et al 2007, Braulke & Bonifacino 2009, Blanz et al 2010].
  • Third, LIMP-2 has recently been found to represent a substrate for cathepsin-F, the enzyme involved in ANCL (Kufs disease) type B, suggesting that there may be links between the pathogenesis of different forms of PME.

In addition, an extralysosomal function has been discovered in mice, human hearts, and myocytes in vivo, in which LIMP-2 has been identified as an important component of the structural organization of the cardiac myocyte intercalated disc, in particular adherens junctions, where it interacts with N-cadherin [Schroen et al 2007].

SCARB2 protein also functions as a receptor for various viruses.

Abnormal gene product. Action myoclonus – renal failure syndrome (AMRF) is caused by deficiency of the SCARB2 protein.

In AMRF, the beta-glucocerebrosidase (β-GC) structure itself is not affected, but its receptor in the trans-Golgi network (TGN) is abnormal, therefore altering its trafficking along its biosynthetic pathway. Biochemical analysis reveals a severe deficiency of β-GC in skin fibroblasts despite normal enzyme activity on standard leukocyte screening assays (Family D in Badhwar et al [2004]; unpublished data) [Balreira et al 2008, Zeigler et al 2014].

This selective tissue involvement could be due to variable expression of the SCARB2 protein or to a variable pathway for the transport of β-GC, specific to tissue. Another hypothesis could be that SCARB2 is also a transporter of other as-yet unidentified proteins that also accumulate and/or are secreted in excess [Amrom et al 2017].

AMRF is remarkable for the preservation of normal intelligence in the majority of patients. This could be explained by the observation of extraneuronal but no intraneuronal storage of autofluorescent pigmented material [Andermann et al 1986, Badhwar et al 2004]. However, two Japanese patients with AMRF developed dementia; it is unclear whether this is linked to AMRF or whether these patients had a second disease [Fu et al 2014]. Autofluorescent pigmented granules were observed in the cytoplasm of the astrocytes in these patients. Neuropathologic studies are needed in order to identify the nature of the storage material and to better localize the cellular organelles at the site of storage.

Animal models. The limp-2/scarb2-/- knockout mice showed a triad encompassing pelvic junction obstruction, deafness, and peripheral demyelinating neuropathy [Gamp et al 2003].

Fluorescence immunohistochemical studies in these mice showed that deafness was due to an early loss of potassium channel KCNQ1/KCNE1 surface expression in marginal cells of the stria vascularis in the cochlea [Knipper et al 2006]. In vivo studies in mice lacking limp-2 have shown that β-GC is no longer sorted to lysosomes but is secreted into the extracellular environment [Reczek et al 2007].

In the limp-2 null mice, embryologic cardiac development is normal; however, these mice fail to mount a hypertrophic cardiac response to AngII-induced hypertension, and develop dilated cardiomyopathy. limp-2 protein was thus shown to not only be an important lysosomal protein but also to be an important part of the intercalated disc of the heart and crucial for the hypertrophic response to cardiac loading [Schroen et al 2007].

References

Literature Cited

  • Amrom D, Andermann F, Dibbens L, Berkovic S, Schwake M, Saftig P, Andermann E. Action myoclonus with renal failure syndrome (AMRF). In: Minassian BA, Striano P, Avanzini G, eds. Progressive Myoclonus Epilepsies. New Barnet, UK: John Libbey. 2017.
  • Andermann E, Andermann F, Carpenter S, Wolfe LS, Nelson R, Patry G, Boileau J. Action myoclonus-renal failure syndrome: a previously unrecognized neurological disorder unmasked by advances in nephrology. Adv Neurol. 1986;43:87–103. [PubMed: 3946122]
  • Andermann E. Action myoclonus – renal failure syndrome. In: Shorvon SD, Andermann F, Guerrini R, eds. The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. Cambridge, UK: Cambridge University Press; 2011:169-71.
  • Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V, Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet. 2011;88:566–73. [PMC free article: PMC3146726] [PubMed: 21549341]
  • 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. Action myoclonus-renal failure syndrome: characterization of a unique cerebro-renal disorder. Brain. 2004;127:2173–82. [PubMed: 15364701]
  • Balreira A, Gaspar P, Caiola D, Chaves J, Beirao I, Lima JL, Azevedo JE, Miranda MC. A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome. Hum Mol Genet. 2008;17:2238–43. [PubMed: 18424452]
  • Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach HL, Wu S, Nashelsky M, Vladar EK, Antic D, Ferguson PJ, Cirak S, Voit T, Scott MP, Axelrod JD, Gurnett C, Daoud AS, Kivity S, Neufeld MY, Mazarib A, Straussberg R, Walid S, Korczyn AD, Slusarski DC, Berkovic SF, El-Shanti HI. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet. 2008;83:572–81. [PMC free article: PMC2668041] [PubMed: 18976727]
  • Berkovic SF, Carpenter S, Andermann F, Andermann E, Wolfe LS. Kuf's disease: a critical reappraisal. Brain. 1988;111:27–62. [PubMed: 3284607]
  • Berkovic SF, Dibbens LM, Oshlack A, Silver JD, Katerelos M, Vears DF, Lullmann-Rauch R, Blanz J, Zhang KW, Stankovich J, Kalnins RM, Dowling JP, Andermann E, Andermann F, Faldini E, D'Hooge R, Vadlamudi L, Macdonell RA, Hodgson BL, Bayly MA, Savige J, Mulley JC, Smyth GK, Power DA, Saftig P, Bahlo M. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am J Hum Genet. 2008;82:673–84. [PMC free article: PMC2427287] [PubMed: 18308289]
  • Berkovic SF, Mazarib A, Walid S, Neufeld MY, Manelis J, Nevo Y, Korczyn AD, Yin J, Xiong L, Pandolfo M, Mulley JC, Wallace RH. A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping. Brain. 2005;128:652–8. [PubMed: 15634728]
  • Bindoff LA, Engelsen BA. Mitochondrial diseases and epilepsy. Epilepsia. 2012;53 Suppl 4:92–7. [PubMed: 22946726]
  • Bird TD, Shaw CM. Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 1978;41:140–9. [PMC free article: PMC492982] [PubMed: 632821]
  • Blanz J, Groth J, Zachos C, Wehling C, Saftig P, Schwake M. Disease-causing mutations within the lysosomal integral membrane protein type 2 (LIMP-2) reveal the nature of binding to its ligand beta-glucocerebrosidase. Hum Mol Genet. 2010;19:563–72. [PubMed: 19933215]
  • Bonten EJ, Arts WF, Beck M, Covanis A, Donati MA, Parini R, Zammarchi E, d'Azzo A. Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis. Hum. Molec. Genet. 2000;9:2715–25. [PubMed: 11063730]
  • Boustany RM. Lysosomal storage diseases--the horizon expands. Nat Rev Neurol. 2013;9:583–98. [PubMed: 23938739]
  • Boyer O, Nevo F, Plaisier E, Funalot B, Gribouval O, Benoit G. Huynh Cong E, Arrondel C, Tête MJ, Montjean R, Richard L, Karras A, Pouteil-Noble C, Balafrej L, Bonnardeaux A, Canaud G, Charasse C, Dantal J, Deschenes G, Deteix P, Dubourg O, Petiot P, Pouthier D, Leguern E, Guiochon-Mantel A, Broutin I, Gubler MC, Saunier S, Ronco P, Vallat JM, Alonso MA, Antignac C, Mollet G. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. N Engl J Med. 2011;365:2377–88. [PubMed: 22187985]
  • Braulke T, Bonifacino JS. Sorting of lysosomal proteins. Biochim Biophys Acta. 2009;1793:605–14. [PubMed: 19046998]
  • Brown P. Action myoclonus-renal failure syndrome: the definitive clinico-pathological description. Brain. 2004;127:2151–2. [PubMed: 15385427]
  • Burneo JG, Arnold T, Palmer CA, Kuzniecky RI, Oh SJ, Faught E. Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama. Epilepsia. 2003;44:841–6. [PubMed: 12790899]
  • Cadieux-Dion M, Andermann E, Lachance-Touchette P, Ansorge O, Meloche C, Barnabé A, Kuzniecky RI, Andermann F, Faught E, Leonberg S, Damiano JA, Berkovic SF, Rouleau GA, Cossette P. Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease. Clin Genet. 2013;83:571–5. [PubMed: 22978711]
  • Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin CA, Rouleau GA, Nguyen DK, Cossette P. Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol. 2014;71:470–5. [PubMed: 24566826]
  • Carpenter S, Karpati G, Andermann F, Jacob JC, Andermann E. Lafora's disease: peroxisomal storage in skeletal muscle. Neurology. 1974;24:531–8. [PubMed: 4220225]
  • Carpenter S, Karpati G. Sweat gland duct cells in Lafora disease: diagnosis by skin biopsy. Neurology. 1981;31:1564–8. [PubMed: 6796905]
  • Chan EM, Young EJ, Ianzano L, Munteanu I, Zhao X, Christopoulos CC, Avanzini G, Elia M, Ackerley CA, Jovic NJ, Bohlega S, Andermann E, Rouleau GA, Delgado-Escueta AV, Minassian BA, Scherer SW. Mutations in NHLRC1 cause progressive myoclonus epilepsy. Nat Genet. 2003;35:125–7. [PubMed: 12958597]
  • Chaves J, Beirao I, Balreira A, Gaspar P, Caiola D, Sa-Miranda MC, Lima JL. Progressive myoclonus epilepsy with nephropathy C1q due to SCARB2/LIMP-2 deficiency: clinical report of two siblings. Seizure. 2011;20:738–40. [PubMed: 21782476]
  • Coppola A, Santulli L, Del Gaudio L, Minetti C, Striano S, Zara F, Striano P. Natural history and long-term evolution in families with autosomal dominant cortical tremor, myoclonus, and epilepsy. Epilepsia. 2011 Jul;52(7):1245–50. [PubMed: 21426326]
  • Costello DJ, Chiappa KH, Siao P. Progressive myoclonus epilepsy with demyelinating peripheral neuropathy and preserved intellect: a novel syndrome. Arch Neurol. 2009;66:898–901. [PubMed: 19597094]
  • Crompton DE, Sadleir LG, Bromhead CJ, Bahlo M, Bellows ST, Arsov T, Harty R, Lawrence KM, Dunne JW, Berkovic SF, Scheffer IE. Familial adult myoclonic epilepsy: recognition of mild phenotypes and refinement of the 2q locus. Arch Neurol. 2012 Apr;69(4):474–81. [PubMed: 22491192]
  • Dahl N, Erikson A, Hammarstrom-Heeroma K, Pettersson U. Tight linkage between type III Gaucher's disease (Norrbottnian type) and a MspI polymorphism within the gene for human glucocerebrosidase. Genomics. 1988;3:296–8. [PubMed: 2468600]
  • Depienne C, Magnin E, Bouteiller D, Stevanin G, Saint-Martin C, Vidailhet M, Apartis E, Hirsch E, LeGuern E, Labauge P, Rumbach L. Familial cortical myoclonic tremor with epilepsy: the third locus (FCMTE3) maps to 5p. Neurology. 2010;74:2000–3. [PubMed: 20548044]
  • Dibbens LM, Karakis I, Bayly MA, Costello DJ, Cole AJ, Berkovic SF. Mutation of SCARB2 in a patient with progressive myoclonus epilepsy and demyelinating peripheral neuropathy. Arch Neurol. 2011;68:812–3. [PubMed: 21670406]
  • 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. SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure. Ann Neurol. 2009;66:532–6. [PubMed: 19847901]
  • Eskelinen EL, Tanaka Y, Saftig P. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 2003;13:137–45. [PubMed: 12628346]
  • Finsterer J, Zarrouk Mahjoub S. Epilepsy in mitochondrial disorders. Seizure. 2012;21:316–21. [PubMed: 22459315]
  • Fu YJ, Aida I, Tada M, Tada M, Toyoshima Y, Takeda S, Nakajima T, Naito H, Nishizawa M, Onodera O, Kakita A, Takahashi H. Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of Japanese patients with novel SCARB2 mutations. Neuropathol Appl Neurobiol. 2014;40:551–63. [PubMed: 23659519]
  • Gamp AC, Tanaka Y, Lullmann-Rauch R, Wittke D, D'Hooge R, De Deyn PP, Moser T, Maier H, Hartmann D, Reiss K, Illert AL, von Figura K, Saftig P. LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice. Hum Mol Genet. 2003;12:631–46. [PubMed: 12620969]
  • Genton P, Thomas P, Kasteleijn-Nolst Trenite DG, Medina MT, Salas-Puig J. Clinical aspects of juvenile myoclonic epilepsy. Epilepsy Behav. 2013;28 Suppl 1:S8–14. [PubMed: 23756488]
  • Genton P. Unverricht-Lundborg disease (EPM1). Epilepsia. 2010;51 Suppl 1:37–9. [PubMed: 20331711]
  • Guerrero-López R, García-Ruiz PJ, Giráldez BG, Durán-Herrera C, Querol-Pascual MR, Ramírez-Moreno JM, Más S, Serratosa JM. A new SCARB2 mutation in a patient with progressive myoclonus ataxia without renal failure. Mov Disord. 2012;27:1826–7. [PubMed: 23225201]
  • Guerrini R, Bonanni P, Patrignani A, Brown P, Parmeggiani L, Grosse P, Brovedani P, Moro F, Aridon P, Carrozzo R, Casari G. Autosomal dominant cortical myoclonus and epilepsy (ADCME) with complex partial and generalized seizures: A newly recognized epilepsy syndrome with linkage to chromosome 2p11.1-q12.2. Brain. 2001;124:2459–75. [PubMed: 11701600]
  • Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 1998;39:508–12. [PubMed: 9596203]
  • Hagen MC, Murrell JR, Delisle MB, Andermann E, Andermann F, Guiot MC, Ghetti B. Encephalopathy with neuroserpin inclusion bodies presenting as progressive myoclonus epilepsy and associated with a novel mutation in the Proteinase Inhibitor 12 gene. Brain Pathol. 2011;21:575–82. [PMC free article: PMC3709456] [PubMed: 21435071]
  • Harris CM, Taylor DS, Vellodi A. Ocular motor abnormalities in Gaucher disease. Neuropediatrics. 1999;30:289–93. [PubMed: 10706022]
  • He M, Tang BS, Li N, Mao X, Li J, Zhang JG, Xiao JJ, Wang J, Jiang H, Shen L, Guo JF, Xia K, Wang JL. Using a combination of whole-exome sequencing and homozygosity mapping to identify a novel mutation of SCARB2. Clin Genet. 2014;86:598–600. [PubMed: 24620919]
  • Higashiyama Y, Doi H, Wakabayashi M, Tsurusaki Y, Miyake N, Saitsu H, Ohba C, Fukai R, Miyatake S, Joki H, Koyano S, Suzuki Y, Tanaka F, Kuroiwa Y, Matsumoto N. A novel SCARB2 mutation causing late-onset progressive myoclonus epilepsy. Mov Disord. 2013;28:552–3. [PubMed: 23325613]
  • Hopfner F, Schormair B, Knauf F, Berthele A, Tolle TR, Baron R, Maier C, Treede RD, Binder A, Sommer C, Maihofner C, Kunz W, Zimprich F, Heemann U, Pfeufer A, Nabauer M, Kaab S, Nowak B, Gieger C, Lichtner P, Trenkwalder C, Oexle K, Winkelmann J. Novel SCARB2 mutation in action myoclonus-renal failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features. BMC Neurol. 2011;11:134. [PMC free article: PMC3222607] [PubMed: 22032306]
  • Ikeda A, Kakigi R, Funai N, Neshige R, Kuroda Y, Shibasaki H. Cortical tremor: a variant of cortical reflex myoclonus. Neurology. 1990;40:1561–5. [PubMed: 2215948]
  • Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E. Clinical picture of EPM1-Unverricht-Lundborg disease. Epilepsia. 2008;49:549–56. [PubMed: 18325013]
  • Klein C. Myoclonus and myoclonus-dystonias. In: Pulst S, ed. Genetics of Movement Disorders. San Diego, CA: Academic Press; 2002:449-69.
  • Knipper M, Claussen C, Ruttiger L, Zimmermann U, Lullmann-Rauch R, Eskelinen EL, Schroder J, Schwake M, Saftig P. Deafness in LIMP2-deficient mice due to early loss of the potassium channel KCNQ1/KCNE1 in marginal cells of the stria vascularis. J Physiol. 2006;576:73–86. [PMC free article: PMC1995639] [PubMed: 16901941]
  • Martí-Massó JF, Bergareche A, Makarov V, Ruiz-Martinez J, Gorostidi A, López de Munain A, Poza JJ, Striano P, Buxbaum JD, Paisán-Ruiz C. The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. J Mol Med (Berl). 2013;91:1399–406. [PMC free article: PMC3833949] [PubMed: 23955123]
  • Minassian BA, Lee JR, Herbrick JA, Huizenga J, Soder S, Mungall AJ, Dunham I, Gardner R, Fong CY, Carpenter S, Jardim L, Satishchandra P, Andermann E, Snead OC, Lopes-Cendes I, Tsui LC, Delgado-Escueta AV, Rouleau GA, Scherer SW. Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Nat Genet. 1998;20:171–4. [PubMed: 9771710]
  • Mink JW, Augustine EF, Adams HR, Marshall FJ, Kwon JM. Classification and natural history of the neuronal ceroid lipofuscinoses. J Child Neurol. 2013;28:1101–5. [PMC free article: PMC3979348] [PubMed: 23838030]
  • Mitchison HM, Hofmann SL, Becerra CH, Munroe PB, Lake BD, Crow YJ, Stephenson JB, Williams RE, Hofman IL, Taschner PE, Martin JJ, Philippart M, Andermann E, Andermann F, Mole SE, Gardiner RM, O'Rawe AM. Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits. Hum Mol Genet. 1998;7:291–7. [PubMed: 9425237]
  • Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, Joensuu T, Canafoglia L, Franceschetti S, Michelucci R, Markkinen S, Heron SE, Hildebrand MS, Andermann E, Andermann F, Gambardella A, Tinuper P, Licchetta L, Scheffer IE, Criscuolo C, Filla A, Ferlazzo E, Ahmad J, Ahmad A, Baykan B, Said E, Topcu M, Riguzzi P, King MD, Ozkara C, Andrade DM, Engelsen BA, Crespel A, Lindenau M, Lohmann E, Saletti V, Massano J, Privitera M, Espay AJ, Kauffmann B, Duchowny M, Møller RS, Straussberg R, Afawi Z, Ben-Zeev B, Samocha KE, Daly MJ, Petrou S, Lerche H, Palotie A, Lehesjoki A. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet. 2015;47:39–46. [PMC free article: PMC4281260] [PubMed: 25401298]
  • Nijssen PC, Ceuterick C, van Diggelen OP, Elleder M, Martin JJ, Teepen JL, Tyynelä J, Roos RA. Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with granular osmiophilic deposits without palmitoyl protein thioesterase 1 deficiency. Brain Pathol. 2003;13:574–81. [PMC free article: PMC8095852] [PubMed: 14655761]
  • Nosková L, Stránecký V, Hartmannová H, Přistoupilová A, Barešová V, Ivánek R, Hůlková H, Jahnová H, van der Zee J, Staropoli JF, Sims KB, Tyynelä J, Van Broeckhoven C, Nijssen PC, Mole SE, Elleder M, Kmoch S. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am J Hum Genet. 2011;89:241–52. [PMC free article: PMC3155175] [PubMed: 21820099]
  • Perandones C, Micheli FE, Pellene LA, Bayly MA, Berkovic SF, Dibbens LM. A case of severe hearing loss in action myoclonus renal failure syndrome resulting from mutation in SCARB2. Mov Disord. 2012;27:1200–1. [PubMed: 22767442]
  • Perandones C, Pellene LA, Micheli F. Reply: A new SCARB2 mutation in a patient with progressive myoclonus ataxia without renal failure. Mov Disord. 2014;29:158–9. [PubMed: 24339182]
  • Ramadan H, Al-Din AS, Ismail A, Balen F, Varma A, Twomey A, Watts R, Jackson M, Anderson G, Green E, Mole SE. Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1. Neurology. 2007;68:387–8. [PubMed: 17261688]
  • Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, Brondyk W, Van Patten S, Edmunds T, Saftig P. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007;131:770–83. [PubMed: 18022370]
  • Roze E, Apartis E, Clot F, Dorison N, Thobois S, Guyant-Marechal L, Tranchant C, Damier P, Doummar D, Bahi-Buisson N, André-Obadia N, Maltete D, Echaniz-Laguna A, Pereon Y, Beaugendre Y, Dupont S, De Greslan T, Jedynak CP, Ponsot G, Dussaule JC, Brice A, Dürr A, Vidailhet M. Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations. Neurology. 2008;70:1010–6. [PubMed: 18362280]
  • Rubboli G, Franceschetti S, Berkovic SF, Canafoglia L, Gambardella A, Dibbens LM, Riguzzi P, Campieri C, Magaudda A, Tassinari CA, Michelucci R. Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by SCARB2 mutations. Epilepsia. 2011;52:2356–63. [PubMed: 22050460]
  • Schroen B, Leenders JJ, van Erk A, Bertrand AT, van Loon M, van Leeuwen RE, Kubben N, Duisters RF, Schellings MW, Janssen BJ, Debets JJ, Schwake M, Hoydal MA, Heymans S, Saftig P, Pinto YM. Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. J Exp Med. 2007;204:1227–35. [PMC free article: PMC2118572] [PubMed: 17485520]
  • Sleat DE, Ding L, Wang S, Zhao C, Wang Y, Xin W, Zheng H, Moore DF, Sims KB, Lobel P. Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology. Mol Cell Proteomics. 2009;8:1708–18. [PMC free article: PMC2709195] [PubMed: 19383612]
  • Smith KR, Dahl HH, Canafoglia L, Andermann E, Damiano J, Morbin M, Bruni AC, Giaccone G, Cossette P, Saftig P, Grötzinger J, Schwake M, Andermann F, Staropoli JF, Sims KB, Mole SE, Franceschetti S, Alexander NA, Cooper JD, Chapman HA, Carpenter S, Berkovic SF, Bahlo M. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum Mol Genet. 2013;22:1417–23. [PMC free article: PMC3596852] [PubMed: 23297359]
  • Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF, Sims KB, Lewis J, Lin WL, Dickson DW, Dahl HH, Bahlo M, Berkovic SF. Strikingly different clinicopathological phenotypes determined by progranulin mutation dosage. Am J Hum Genet. 2012;90:1102–7. [PMC free article: PMC3370276] [PubMed: 22608501]
  • Stogmann E, Reinthaler E, Eltawil S, El Etribi MA, Hemeda M, El Nahhas N, Gaber AM, Fouad A, Edris S, Benet-Pages A, Eck SH, Pataraia E, Mei D, Brice A, Lesage S, Guerrini R, Zimprich F, Strom TM, Zimprich A. Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2. Brain. 2013;136:1155–60. [PubMed: 23518707]
  • Striano P, Robbiano A, Zara F, Striano S. Familial cortical tremor and epilepsy: a well-defined syndrome with genetic heterogeneity waiting for nosological placement in the ILAE classification. Epilepsy Behav. 2010;19:669. [PubMed: 20974551]
  • Takano H, Cancel G, Ikeuchi T, Lorenzetti D, Mawad R, Stevanin G, Didierjean O, Dürr A, Oyake M, Shimohata T, Sasaki R, Koide R, Igarashi S, Hayashi S, Takiyama Y, Nishizawa M, Tanaka H, Zoghbi H, Brice A, Tsuji S. Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations. Am J Hum Genet. 1998;63:1060–6. [PMC free article: PMC1377499] [PubMed: 9758625]
  • Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh NS, Yang T, Wu S, Chen S, Fox MH, Gurnett C, Montine T, Bird T, Shaffer LG, Rosenfeld JA, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto RP, Scott MP, Antic D, Reed J, Boland R, Ehaideb SN, El-Shanti H, Mahajan VB, Ferguson PJ, Axelrod JD, Lehesjoki AE, Fritzsch B, Slusarski DC, Wemmie J, Ueno N, Bassuk AG. Mutations in prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet. 2011;88:138–49. [PMC free article: PMC3035715] [PubMed: 21276947]
  • Tsuji S, Choudary PV, Martin BM, Stubblefield BK, Mayor JA, Barranger JA, Ginns EI. A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. New Eng J Med. 1987;316:570–5. [PubMed: 2880291]
  • Tsuji S. Dentatorubral-pallidoluysian atrophy. Handb Clin Neurol. 2012;103:587–94. [PubMed: 21827919]
  • Vadlamudi L, Vears DF, Hughes A, Pedagogus E, Berkovic SF. Action myoclonus-renal failure syndrome: a cause for worsening tremor in young adults. Neurology. 2006;67:1310–1. [PubMed: 17030781]
  • van Diggelen OP, Thobois S, Tilikete C, Zabot MT, Keulemans JL, van Bunderen PA, Taschner PE, Losekoot M, Voznyi YV. Adult neuronal ceroid lipofusciosis with palmitoyl-proteinthioesterase deficiency: first adultt-onset patients of a childhood disease. Ann Neurol. 2001;50:269–72. [PubMed: 11506414]
  • Velayati A, DePaolo J, Gupta N, Choi JH, Moaven N, Westbroek W, Goker-Alpan O, Goldin E, Stubblefield BK, Kolodny E, Tayebi N, Sidransky E. A mutation in SCARB2 is a modifier in Gaucher disease. Hum Mutat. 2011;32:1232–8. [PMC free article: PMC3196787] [PubMed: 21796727]
  • Xin W, Mullen TE, Kiely R, Min J, Feng X, Cao Y, O'Malley L, Shen Y, Chu-Shore C, Mole SE, Goebel HH, Sims K. CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL. Neurology. 2010;74:565–71. [PubMed: 20157158]
  • Yamayoshi S, Fujii K, Koike S. Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases. Front Microbiol. 2012a;3:32. [PMC free article: PMC3277273] [PubMed: 22363322]
  • Yamayoshi S, Iizuka S, Yamashita T, Minagawa H, Mizuta K, Okamoto M, Nishimura H, Sanjoh K, Katsushima N, Itagaki T, Nagai Y, Fujii K, Koike S. Human SCARB2-dependent infection by coxsackievirus A7, A14, and A16 and enterovirus 71. J Virol. 2012b;86:5686–96. [PMC free article: PMC3347270] [PubMed: 22438546]
  • Yamayoshi S, Ohka S, Fujii K, Koike S. Functional comparison of SCARB2 and PSGL1 as receptors for enterovirus 71. J Virol. 2013;87:3335–47. [PMC free article: PMC3592140] [PubMed: 23302872]
  • Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, Koike S. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med. 2009;15:798–801. [PubMed: 19543282]
  • 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. A novel SCARB2 mutation in progressive myoclonus epilepsy indicated by reduced beta-glucocerebrosidase activity. J Neurol Sci. 2014;339:210–3. [PubMed: 24485911]
  • Zifkin B, Andermann E, Andermann F. Mechanisms, genetics, and pathogenesis of juvenile myoclonic epilepsy. Curr Opin Neurol. 2005;18:147–53. [PubMed: 15791145]
  • Zimprich A, Grabowski M, Asmus F, Naumann M, Berg D, Bertram M, Scheidtmann K, Kern P, Winkelmann J, Müller-Myhsok B, Riedel L, Bauer M, Müller T, Castro M, Meitinger T, Strom TM, Gasser T. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. Nat Genet. 2001;29:66–9. [PubMed: 11528394]

Chapter Notes

Revision History

  • 17 December 2015 (me) Review posted live
  • 25 February 2014 (da) Original submission
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