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SCARB2-Related Action Myoclonus – Renal Failure Syndrome

, MD, , MD, , MD, and , MD.

Author Information and Affiliations

Initial Posting: ; Last Update: February 9, 2023.

Estimated reading time: 34 minutes

Summary

Clinical characteristics.

SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal involvement that is apparently due to steroid-resistant nephrotic syndrome (SRNS). The neurologic and renal manifestations progress independently. In some instances, renal involvement is not observed; thus, PME without renal manifestations caused by biallelic SCARB2 pathogenic variants is considered to be one end of the spectrum of SCARB2-AMRF. All individuals reported to date developed neurologic findings; in some instances renal manifestations predated neurologic involvement by decades. The disease progresses relentlessly, with neurologic deterioration (especially increasing severity of myoclonus) and/or end-stage kidney disease (ESKD) leading to death within seven to 15 years after onset.

Diagnosis/testing.

The diagnosis of SCARB2-AMRF is established in a proband with suggestive findings and biallelic loss-of-function pathogenic variants in SCARB2 identified by molecular genetic testing.

Management.

Treatment of manifestations: There is no cure for SCARB2-AMRF.

The supportive care for neurologic manifestations that is recommended to improve quality of life, maximize function, and reduce complications includes pharmacotherapy to reduce myoclonus; anti-seizure medication (ASM) and vagus nerve stimulation to reduce seizures; physical and occupational therapy to help maintain mobility and optimize activities of daily living; adaptive devices to help maintain/improve independence in mobility; educational support for those with cognitive decline; speech-language therapy to explore use of alternative communication methods; feeding therapy programs for those with dysphagia to improve nutrition and reduce aspiration risk.

Treatment for renal involvement, under the care of a nephrologist, is typically focused on remission of proteinuria and often includes a combination of renin-angiotensin-aldosterone inhibition and immunosuppressive medications. Treatment of ESKD is supportive; while renal replacement therapy can prolong survival, it does not improve neurologic features.

Surveillance: Regular follow up with multidisciplinary care providers to monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations.

Agents/circumstances to avoid: Phenytoin may aggravate neurologic manifestations or even accelerate cerebellar degeneration; sodium channel blockers (carbamazepine, oxcarbazepine), GABAergic drugs (tiagabine, vigabatrin), and gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures.

Pregnancy management: Some ASMs can increase the risk of malformations, growth restriction, and/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 pregnant women with a known seizure disorder continue to take ASMs and that the prescribing physician follow standard measures to prevent fetopathy, including possible changes of medication prior to pregnancy; spacing of ASMs during pregnancy into four doses a day or taking extended-release medications, so that ASM levels do not have significant peaks or troughs; monitoring ASM dosages and levels during pregnancy.

In addition, all women of childbearing age should be advised to take 1 mg/day of folic acid and to increase it to 4 mg/day when planning a pregnancy (ideally three months prior to conception) and during the pregnancy, in order to reduce the risk of congenital malformations that can be associated with fetal exposure to ASMs.

Genetic counseling.

SCARB2-AMRF is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a SCARB2 pathogenic variant, each sib of an affected individual has at conception 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. Once the SCARB2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.

Diagnosis

No consensus clinical diagnostic criteria for SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) have been published.

Suggestive Findings

SCARB2-AMRF should be suspected in a previously healthy teenager or young adult with the following neurologic and renal manifestations, especially if family history is suggestive of an autosomal recessive disorder [Andermann 2011, Tian et al 2018, Atasu et al 2022].

Neurologic manifestations

  • Tremor, which is commonly the first finding, initially manifests in the fingers and hands during actions such as the fine motor activities involved in handwriting. The tremor, which is cortical in nature, is usually absent at rest and is relieved by alcohol.
    The tremor can later involve the head, trunk, lower extremities, and sometimes tongue and voice. In the later stages of the disease, it may become masked by striking myoclonic jerks.
  • Involuntary, action-induced myoclonic jerks including orolingual myoclonic jerks induced by attempts to speak or swallow. Myoclonus could be multifocal or generalized. There is a sensory-reflex myoclonic response to sensory stimulation, particularly to tendon stretch; the reflex response may spread beyond the stimulated body segment.
  • Involuntary spontaneous myoclonic jerks of the face (particularly perioral) as well as synchronous and asynchronous jerks of the trunk and limbs at rest could be present but are certainly less prevalent than those induced by action.
  • Generalized tonic-clonic, myoclonic, and mixed seizure types might occur during wakefulness or sleep. A crescendo of myoclonic jerks might herald seizures.
  • Other findings can include:
    • Sensorimotor peripheral neuropathy (most often predominantly demyelinating or more rarely axonal);
    • Sensorineural hearing loss.
  • Cerebellar ataxia and cerebellar degeneration are common later in the disease course. Note that myoclonus, which occurs during the kinetic phase of movements, leads to dysmetria (myoclonic dysmetria) and is often confused for limb ataxia. At least one individual with SCARB2-AMRF was identified in a spinocerebellar ataxia cohort despite the fact that myoclonic seizures and dementia were also present [Guan et al 2020].

Renal manifestations

  • Proteinuria, the first manifestation of kidney disease, is initially mild and asymptomatic.
  • Kidney disease can progress to nephrotic syndrome and end-stage kidney disease.
  • Common histologic findings on kidney biopsy include tubular abnormalities and focal segmental glomerulosclerosis.
  • In some families, renal manifestations appear first in late childhood or the early teenage years and neurologic manifestations in the late third or early fourth decade [Badhwar et al 2004].

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of SCARB2-AMRF is established in a proband with suggestive findings and biallelic loss-of-function pathogenic (or likely pathogenic) variants in SCARB2 identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include any likely pathogenic variants. (2) Identification of biallelic SCARB2 variants of uncertain significance (or of one known SCARB2 pathogenic variant and one SCARB2 variant of uncertain significance) does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.

Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas genomic testing does not (see Option 2).

Option 1

A multigene panel for lysosomal storage diseases, nephrotic syndrome, focal segmental glomerulosclerosis, movement disorders, ataxia, or epilepsy (based on the individual's presenting features) that includes SCARB2 and other genes of interest (see Differential Diagnosis) 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. 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. (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.

Option 2

Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.

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 SCARB2-Related Action Myoclonus – Renal Failure Syndrome

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
SCARB2 Sequence analysis 3100% 4
Gene-targeted deletion/duplication analysis 5None reported 4
1.

See Table A. Genes and Databases for chromosome locus and protein.

2.

See Molecular Genetics for information on 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 missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions and duplications. Methods used may include a range of techniques such as 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

SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal involvement that can range from mild proteinuria to steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD) (see Table 2). In some instances, renal involvement is not observed; thus, PME without proteinuria caused by biallelic SCARB2 pathogenic variants is considered to be one end of the spectrum of SCARB2-AMRF [Tian et al 2018, Atasu et al 2022]. Of note, while all reported individuals developed neurologic findings, renal manifestations were reported to predate neurologic involvement by decades in some instances. Thus, the absence of neurologic involvement should not preclude consideration of SCARB2-AMRF in individuals with kidney disease [Badhwar et al 2004].

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

  • Neurologic manifestations can appear before (in one third of affected individuals), simultaneously, or after renal manifestations. In juvenile SCARB2-AMRF, onset is usually in the late teenage years or early in the third decade [Badhwar et al 2004].
  • In some persons renal manifestations occur early (late childhood or early teenage years) and neurologic involvement much later (late in the third decade or early in the fourth decade) [Badhwar et al 2004, Hopfner et al 2011].
  • In three persons of Japanese descent who did not develop SRNS, neurologic manifestations appeared in the fifth or sixth decade [Higashiyama et al 2013, Fu et al 2014]. See Late-Onset SCARB2-AMRF.

The neurologic and renal manifestations progress independently. Of note, the neurologic manifestations are not the result of a metabolic encephalopathy due to renal involvement (chronic kidney disease [CKD] or ESKD) and are not improved by treatment of the renal disease by either dialysis or by kidney transplantation [Andermann et al 1986, Badhwar et al 2004]. The use of anti-rejection medications such as cyclosporine known to induce tremor can mistakenly be blamed for the emergence of myoclonus before a molecular diagnosis of SCARB2-AMRF is established.

Even in the same family, the number and range of clinical manifestations and the order of their appearance can vary. Neurologic manifestations may occur first or in isolation in some family members, and renal manifestations may occur first or in isolation in other family members [Badhwar et al 2004].

Renal manifestations can be variable even within the same family, including proteinuria, reduced creatinine clearance, CKD, or ESKD. Some individuals do not develop kidney disease [Atasu et al 2022].

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

Table 2.

SCARB2-Related Action Myoclonus – Renal Failure Syndrome: Frequency of Select Neurologic Features

FeatureFrequencyComment
Nearly allCommonInfrequent
Progressive action & reflex myoclonus●
Ataxia●Usually late in disease course
Tremor●Action & posture induced, irregular amplitude (cortical tremor)
Myoclonus at rest●
Dysarthria●Usually late in disease course
Severe epileptic photosensitivity●
Generalized tonic-clonic seizures●
Dysphagia●Not discussed in most reports, may be late finding
Cognitive decline●
Sensorineural hearing loss●

Neurologic Disease

Fine tremor. Usually noted in the second or third decade of life beginning with bilateral fine rhythmic tremor of the fingers noted during delicate movement such as isometric contractions or posture, writing, or by intention of movement [Tian et al 2018, Atasu et al 2022]. 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.

Action myoclonus usually appears within ten years of tremor onset (third decade of life) as jerking movements first of the upper extremities and then of the lower extremities. Action myoclonus is typically triggered by movements or intended movements. Action myoclonus can be asynchronous, multifocal, and of variable severity. Action myoclonus can also be reflex sensitive to touch over the distal extremities and can be exacerbated by anxiety, excitement, stress, fatigue, auditory stimuli, or startle [Badhwar et al 2004, Perandones et al 2012, Zeigler et al 2014].

With time, myoclonic jerks involve the proximal limbs. Their amplitude and frequency increase 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.

Myoclonus can also be "negative" and characterized by a sudden cessation of postural tone that leads to postural lapses. This is particularly prominent in the standing position, where postural lapses of the antigravity muscles create a "bouncing" stance [Toro et al 1995].

Action myoclonus is often the most disabling neurologic manifestation and may prevent affected individuals from performing activities of daily living such as speaking, swallowing food, or walking [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. They represent the absence of complete relaxation. Ocular dysmetria can occur later in the disease course.

Seizures, a common feature of SCARB2-AMRF, usually present within a few years of myoclonus (second or third decade of life). Both myoclonic seizures and generalized tonic-clonic seizures (in some instances progressing to status epilepticus) have been described. Seizures can be diurnal or nocturnal. Light stimulation, eye closure, and TV viewing have all been reported triggers [Rubboli et al 2011].

EEG findings. Although background activity may be normal in some individuals, over time it slowly progresses to include diffuse slowing at 6.5-7.5 Hz. Low-voltage spike and spike/polyspike-wave discharges may be present [Badhwar et al 2004]. As in most PME syndromes, myoclonic jerks are often preceded by a contralateral and somatotopically organized cortical discharge originating in the motor cortex (cortical or epileptic myoclonus).

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

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].

Ataxia and dysarthria. Both are commonly seen later in the disease course (i.e., a few years after onset of myoclonus). Some individuals who develop significant progressive ataxia before or around the appearance of myoclonus and/or myoclonic dysmetria that is interpreted as cerebellar in origin have been reported to have "progressive myoclonus ataxia" or recessive spinocerebellar ataxia [Guan et al 2020, Atasu et al 2022].

Peripheral neuropathy. In some families, a sensorimotor peripheral neuropathy (both demyelinating and axonal neuropathy) may be present [Atasu et al 2022].

Some affected individuals may be diagnosed with a predominantly demyelinating peripheral neuropathy before the onset of renal involvement [Badhwar et al 2004, Costello et al 2009, Dibbens et al 2011, Hopfner et al 2011].

Sensorineural hearing loss / deafness can be clinically evident or subclinical even within the same family. Three individuals from a German family and another individual from Australia developed hearing loss in adulthood. Family members with subclinical hearing changes have also been reported [Rubboli et al 2011, Perandones et al 2014].

Cognitive function. While the majority of individuals with SCARB2-AMRF have not been reported to have cognitive impairment, four different families were reported to have dementia, cognitive impairment, and executive dysfunction [Fu et al 2014, Atasu et al 2022].

Brain MRI may show cerebral, cerebellar, brain stem, or cortical atrophy. Normal MRIs have also been reported [Tian et al 2018].

Renal Disease

The initial manifestation of renal disease is mild proteinuria that may progress to nephrotic syndrome and ultimately to end-stage kidney disease (ESKD). In 15 individuals with AMRF, proteinuria, which occurred in all individuals, was detected between ages nine and 30 years (mean: 20.1 years, median: 19 years); in 12 individuals progression to ESKD requiring dialysis or kidney transplant occurred within zero to eight years of diagnosis (mean: 3.8 years, median: 4.5 years) [Badhwar et al 2004].

The renal manifestations may precede or follow the onset of neurologic findings and can be variable, even within the same family. In two sibs with molecularly confirmed SCARB2-AMRF, the sister presented initially with progressive gait difficulty and loss of fine motor skills, and subsequently was found to have proteinuria. In contrast, her brother presented with ESKD secondary to focal segmental glomerulosclerosis (FSGS) and underwent kidney transplantation one year prior to the onset of neurologic manifestations. Of note, another brother had died at age 12 years of ESKD secondary to FSGS [Tanriverdi et al 2022].

In another family, proteinuria was detected in two sisters three to four years following the onset of neurologic manifestations. Both subsequently developed nephrotic syndrome (proteinuria, anasarca, and pleural effusions). One died of Staph aureus and Candida albicans septicemia; the other died of fulminant pneumonia from an unidentified organism [Balreira et al 2008]. Although the treatments they received for the nephrotic syndrome and the details of their infections are not available for review, it is important to note that individuals with proteinuria in the range observed in nephrotic syndrome are at increased risk for infections and hypogammaglobulinemia [Trautmann et al 2020].

Renal histology. FSGS, a histologic pattern of kidney injury affecting the podocytes, is a leading cause of kidney disease worldwide and is a common cause of steroid-resistant nephrotic syndrome (SRNS), defined as a lack of remission after four to six weeks of standard prednisone treatment. FSGS and SRNS are often used interchangeably, but not all FSGS presents with nephrotic syndrome nor are all instances of FSGS steroid resistant.

FSGS can be classified as primary (idiopathic), secondary (infection/inflammation, malignancy, drug related), and genetic. Individuals with genetic forms of FSGS or SRNS are unlikely to benefit from prolonged immunosuppression [Rood et al 2012, Rosenberg & Kopp 2017, Trautmann et al 2020]. In most published case reports of SCARB2-AMRF, the immunosuppression regimens used to treat the renal manifestations are not available for review; hence, the label "SRNS" cannot be accurately applied in those individuals. However, SRNS is presumed based on the progressive and hereditary nature of the renal disease.

Other Findings

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

Mild generalized muscle atrophy was reported in two individuals who exhibited mild generalized reduced tone and no fasciculations [Zeigler et al 2014, He et al 2018]. Although electromyography in one individual showed signs consistent with chronic motor neuron involvement, this has not been reported in any other individuals with SCARB2-AMRF [Zeigler et al 2014].

Late-Onset SCARB2-AMRF

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

Higashiyama et al [2013] reported two sibs with SCARB2-AMRF without kidney 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_1390delGATCCAinsATGCATGCACC.

Fu et al [2014] reported a single affected individual from two other Japanese families, one of whom had late-onset disease. This individual presented with gait changes at age 45 years. Of note, he was homozygous for the same pathogenic variant as the two sibs reported by Higashiyama et al [2013]. The two families with reported late-onset SCARB2-AMRF originate from the same geographic area; however, it is unknown if these variants are identical by descent.

Prognosis

No data on long-term survival exists for SCARB2-AMRF. Sudden death may occur during or after a generalized seizure due to aspiration or sudden unexpected death in epilepsy (SUDEP). Death can also occur due to aspiration pneumonia, ESKD, or rejection of a kidney transplant [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006, Rubboli et al 2011].

Genotype-Phenotype Correlations

No genotype-phenotype correlations have been observed.

Of note, three individuals known to have late-onset disease were homozygous for the SCARB2 pathogenic variant c.1385_1390delGATCCAinsATGCATGCACC. See Clinical Description, Late-Onset SCARB2-AMRF. Two were sibs and the other individual was unrelated; however, all three came from the same geographic area in Japan.

Nomenclature

The title of this GeneReview, SCARB2-related action myoclonus – renal failure syndrome, is based on the dyadic naming approach proposed by Biesecker et al [2021], in which mendelian disorders are designated by combining the mutated gene and resulting phenotype. Because the number and range of clinical manifestations and the order of their appearance can vary among affected individuals, a dyadic naming approach tailored to the specific phenotype seen in a given individual (e.g., SCARB2-related myoclonic ataxia and renal failure or SCARB2-related action myoclonus) may be appropriate in clinical practice [Author, personal observation].

SCARB2-AMRF has also been referred to as the following:

  • Familial myoclonus with renal failure
  • Progressive myoclonus epilepsy with renal failure
  • Epilepsy, progressive myoclonic 4 (EPM4), with or without renal failure. 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.

SCARB2-AMRF was first reported in several French Canadian families [Andermann et al 1986]; it occurs worldwide and appears to be a pan ethnic disease.

Differential Diagnosis

Neurologic Manifestations

At the onset of neurologic manifestations, the differential diagnosis includes other causes of myoclonus such as:

  • Acquired causes including toxic exposure (e.g., medication effects) and Lance-Adams syndrome;
  • Metabolic encephalopathies;
  • Hereditary, non-progressive neurologic conditions (see Table 3).

Table 3.

Hereditary Non-Progressive Myoclonic Disorders in the Differential Diagnosis of SCARB2-Related Action Myoclonus – Renal Failure Syndrome

GeneDisorderMOIClinical CharacteristicsComment
CACNB4
CILK1 (ICK)
CLCN2
EFHC1
GABRA1
GABRD 		Juvenile myoclonic epilepsy (JME) (OMIM PS254770)ADNormal neurologic exam; EEG background activity is undisturbed; myoclonus is not progressive. 1JME, which has a favorable outcome, should be considered at onset of myoclonus.
CNTN2
MARCHF6
RAPGEF2
SAMD12
STARD7
TNRC6A
YEATS2 		Cortical tremor syndrome 2 (OMIM PS601068)AD
AR		Adult-onset cortical myoclonus of extremities & seizures (mainly generalized tonic-clonic, less frequently myoclonic seizures or complex partial seizures) in 40% of affected personsCortical tremor syndrome, which usually has a favorable outcome, should be considered at onset of fine tremor.
SGCE SGCE myoclonus-dystonia (DYT11)AD 3Onset of myoclonus is usually in 1st or 2nd decade of life; myoclonus is subcortical in origin; ~50% of affected persons have segmental dystonia.The assoc of myoclonus & dystonia suggests DYT11. No other neurologic features (in particular ataxia & cognitive deficits) are assoc w/DYT11.

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance

1.
2.

Also referred to as familial adult myoclonic epilepsy (FAME) & familial cortical myoclonic tremor associated with epilepsy (FCMTE)

3.

SGCE myoclonus-dystonia is inherited in an autosomal dominant manner with penetrance determined by the parental origin of the altered SGCE allele: an SGCE pathogenic variant on the paternally derived (expressed) SGCE allele generally results in disease; a pathogenic variant on the maternally derived (silenced) SGCE allele typically does not result in disease.

In individuals with a progressive myoclonic epilepsy (PME) phenotype who do not have biallelic SCARB2 pathogenic variants, the disorders included in Table 4 should be considered.

Table 4.

Disorders with a Progressive Myoclonic Epilepsy Phenotype in the Differential Diagnosis of SCARB2-Related Action Myoclonus – Renal Failure Syndrome

GeneDisorderMOIClinical CharacteristicsComment
ATN1 DRPLA ADPersons w/juvenile onset (age <20 yrs) present w/PME & assoc progressive cognitive deterioration & behavioral changes; those w/adult onset (age >20 yrs) present w/ataxia, choreoathetosis, & dementia.DRPLA is relatively more common in the Japanese population than in other ethnic populations.
ATP13A2 Kufor-Rakeb syndrome (See Neurodegeneration with Brain Iron Accumulation Disorders Overview.)ARJuvenile-onset w/(typically) gait abnormalities & neuropsychiatric changes.
Multiple genes incl:
CLN3
PPT1
TPP		Neuronal ceroid-lipofuscinoses (NCL) (OMIM PS256730)ARPersons w/juvenile-onset NCL (most commonly CLN3 related) typically present before age 10 yrs w/epilepsy, progressive cognitive impairment, & visual impairment.There are many types of NCLs that can present at any age ranging from congenital to adulthood; juvenile & adult-onset NCLs can overlap w/SCARB2-AMRF in age at presentation, cognitive decline, & seizure types; persons w/juvenile-onset NCL typically have ↓ visual acuity.
CSTB PME type 1 (EPM1)ARProgressive myoclonus, epilepsy, & ataxia typically presenting between age 6-15 yrs.Cognition is typically spared & disease may stabilize in adulthood.
CTSA Galactosialidosis (OMIM 256540)ARPME w/cognitive declineCathepsin A contributes to stability of neuraminidase & beta-galactosidase. Affected persons can present as a phenocopy for sialidosis type 1, GM1 gangliosidosis (see GLB1-Related Disorders), or w/mixed features.
EPM2A
NHLRC1 		PME, Lafora type ARVisual hallucinations (occipital epilepsy) & cognitive decline; skin biopsy shows pathognomonic Lafora bodies.
GBA1 (GBA)Gaucher disease (GD) type 3ARPrimary neurologic disease; may have onset age <2 yrs but often has more slowly progressive course w/survival into 3rd or 4th decade.
GOSR2 EPM6 (OMIM 614018)ARAtaxia in 1st 2 yrs of life followed by action myoclonus & seizures typically present in late childhood.Cognition is usually preserved though memory difficulties can occur later in adulthood.
KCNC1 1EPM7 (OMIM 616187)ADClinically similar to EPM1.
KCTD7 EPM3 (neuronal ceroid-lipofuscinoses type 14) (OMIM 611726)ARPME, ataxia, developmental regressionTends to present in early childhood
MT-TF
MT-TH
MT-TI
MT-TK
MT-TL1
MT-TP
MT-TS1
MT-TS2 		MERRF MatMultisystem disorder characterized by myoclonus (often 1st symptom) followed by generalized epilepsy, ataxia, weakness, & dementiaBlood & CSF concentrations of lactate & pyruvate are commonly ↑ at rest & ↑ excessively after moderate activity.
NEU1 Sialidosis type 1 (OMIM 256550)ARPME w/cognitive declineCan be assessed w/neuro-ophthalmologic exam, incl electroretinography
POLG POLG-related ataxia neuropathy spectrum (See POLG-Related Disorders.)ARAtaxia, neuropathy, & (in most but not all affected persons) encephalopathy w/seizures
PRICKLE1 PRICKLE1-related PME w/ataxia (EPM1B) (See PRICKLE1-Related Disorders.)ARAtaxia begins at age 4-5 yrs & evolves to PME w/ataxia & mild or no cognitive decline; impaired upward gaze observed in several affected persons.
SERPINI1 Familial encephalopathy w/neuroserpin inclusion bodies (OMIM 604218)ADAge of onset & clinical manifestations vary considerably; clinical phenotypes range from cognitive decline/dementia, dysarthria, & tremors to various forms of refractory epilepsy incl PME & focal or generalized seizures.

AD = autosomal dominant; AR = autosomal recessive; CSF = cerebrospinal fluid; DRPLA = dentatorubral-pallidoluysian atrophy; Mat = maternal; MERRF = myoclonic epilepsy with ragged red fibers; MOI = mode of inheritance; PME = progressive myoclonic epilepsy

1.

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].

Renal Manifestations

See Genetic Steroid-Resistant Nephrotic Syndrome Overview for genes known to be associated with genetic SRNS.

Primary coenzyme Q10 (CoQ10) deficiency can present with intellectual disability, seizures, or progressive ataxia and SRNS. CoQ10 deficiency is important to consider, as treatment with CoQ10 supplementation can limit disease progress.

INF2-related hereditary neuropathy with focal segmental glomerulonephritis (OMIM 614455) should also be considered in persons with peripheral neuropathy and glomerulonephritis. Inheritance is autosomal dominant. (See also Charcot-Marie-Tooth Hereditary Neuropathy Overview.)

Management

No clinical practice guidelines for the neurologic manifestations of SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) have been published.

Generally, myoclonus and seizure management follow the same guidelines as other PME syndromes [Holmes 2020].

Clinical practice recommendations have been published for the diagnosis and management of steroid-resistant nephrotic syndrome, the likely renal disease of SCARB2-AMRF [Trautmann et al 2020] (full text). See also Genetic Steroid-Resistant Nephrotic Syndrome Overview, Management.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SCARB2-AMRF, the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Recommended Evaluations Following Initial Diagnosis in Individuals with SCARB2-Related Action Myoclonus – Renal Failure Syndrome

System/ConcernEvaluationComment
Neurologic Neurologist assess: myoclonus incl myoclonus w/action, in response to stimuli, & at restUse standardized UMRS.
Seizure type & frequencyObtain baseline EEG.
Cerebellar motor dysfunction (gait & postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades, & smooth pursuit)Use standardized scale to establish baseline for ataxia (BARS, ICARS, or SARA).
Sensorimotor involvementNCV, EMG as needed
Musculoskeletal/ADL By physical medicine & rehab / OT & PTTo assess gross motor & fine motor skills, gait, ambulation, need for adaptive devices, need for ongoing PT/OT
Hearing Audiogram & BAEPAssess for clinical or subclinical SNHL.
Dysarthria Speech-language evalConsider referral to speech-language pathologist.
Ophthalmologic involvement Complete eye examIncl extraocular movement
Cognitive NeuropsychologistCognitive eval to establish baseline
Psychiatric/Emotional PsychiatristEvaluate as needed for depression & supportive therapy.
Development / School performance Developmental assessment
  • To incl motor, adaptive, cognitive, & speech-language eval
  • Eval for special education
SRNS Referral to nephrologist
  • Serum creatinine/BUN; urine protein/creatinine; renal ultrasound exam
  • May require kidney biopsy.
Poor weight gain Gastroenterology / nutrition / feeding team eval
  • To incl eval of aspiration risk & nutritional status
  • Consider eval for gastrostomy tube placement in persons w/dysphagia &/or aspiration risk.
Genetic counseling By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of SCARB2-AMRF to facilitate medical & personal decision making
Family support
& resources 		Assess need for: To facilitate peer support for affected persons & their families
Ethics consultation Clinical ethics servicesAssess health care decisions in the context of the best interest of the child & the values & preferences of the family.

ADL = activities of daily living; BAEP = brain stem auditory evoked potentials; BARS = Brief Ataxia Rating Scale; BUN = blood urea nitrogen; ICARS = International Cooperative Ataxia Rating Scale; EMG = electromyogram; MOI = mode of inheritance; NCV = nerve conduction velocities; OT = occupational therapist/therapy; PT = physical therapist/therapy; SARA = Scale for the Assessment and Rating of Ataxia; SCARB2-AMRF = SCARB2-related action myoclonus – renal failure syndrome; SNHL = sensorineural hearing loss; SRNS = steroid-resistant nephrotic syndrome; UMRS = Unified Myoclonus Rating Scale

1.

Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

There is no cure for SCARB2-AMRF.

Neurologic Manifestations

Supportive care to improve quality of life, maximize function, and reduce complications of neurologic manifestations is recommended. This can include multidisciplinary care by specialists (see Table 6).

Table 6.

Supportive Treatment of Neurologic Manifestations in Individuals with SCARB2-Related Action Myoclonus – Renal Failure Syndrome

Manifestation/ConcernTreatmentConsiderations/Other
Myoclonus Pharmacologic Valproic acid1st drug of choice; diminishes myoclonus & frequency of generalized seizures
ClonazepamFDA approved for treatment of myoclonic seizures; used as add-on therapy 1
Other medicationsSee Agents/Circumstances to Avoid; refer to epileptologist for personalized mgmt.
High-dose piracetamUseful in treatment of myoclonus 2
N-acetylcysteineVariable results 3
Vagus nerve stimulationReduces seizures & significantly improves cerebellar function on neurologic exam 4
Other Avoiding extreme stimuli (lights, noises, stress)
Seizures Anti-seizure medicationFollow standard measures for prevention of aspiration pneumonia & SUDEP
ADL PT/OT
  • PT (balance exercises, gait training, muscle strengthening) to maintain mobility & function 1
  • OT to optimize ADL (incl use of adaptive devices, e.g., weighted eating utensils & dressing hooks)
  • Adaptive devices to maintain/improve independence in mobility (e.g., canes, walkers, motorized chairs)
  • Home adaptations to prevent falls (e.g., grab bars, raised toilet seats) & improve mobility (e.g., ramps to accommodate motorized chairs)
Developmental plateau /
Cognitive decline 		See Developmental Delay / Intellectual Disability / Educational Issues.Persons w/cognitive decline may benefit from the same resources available to those w/intellectual disability.
Dysarthria Speech-language therapyConsider alternative communication methods as needed (e.g., writing pads & digital devices).
Dysphagia Feeding therapy programs to improve nutrition & reduce aspiration risk
  • Video esophagram may help define best food consistency.
  • Education re strategies to mitigate aspiration
  • PEG tube in advanced cases
Hearing loss Per audiologistHearing aids may be of benefit.
SRNS Medical mgmt per treating nephrologistRenal replacement therapy (dialysis, kidney transplantation) if refractory to medical mgmt
Psychiatric comorbidity Per psychiatrist & psychotherapistTreatment needs to be individualized.
Weight Nutrition assessment
  • Consider nutritional & vitamin supplementation to meet dietary needs.
  • Avoid obesity, which can exacerbate difficulties w/ambulation & mobility.
Family support
& resources
  • Social work involvement for parental/caregiver support
  • Home nursing referral
As needed

ADL = activities of daily living; OT = occupational therapy; PEG = percutaneous endoscopic gastrostomy; PT = physical therapy; SRNS = steroid-resistant nephrotic syndrome; SUDEP = sudden unexpected death in epilepsy

1.
2.
3.
4.

Renal Disease

The goal of treatment in FSGS is remission of proteinuria. Treatment often includes a combination of renin-angiotensin-aldosterone system inhibition and immunosuppressive medications such as glucocorticoids, calcineurin inhibitors, mycophenolate mofetil, and rituximab. Therapy should be guided by a nephrologist. Treatment of end-stage kidney disease in SCARB2-AMRF is supportive. Dialysis and kidney transplantation can prolong survival but do not improve the neurologic features.

Developmental Delay / Intellectual Disability / Educational Issues

The following information represents typical management recommendations for school-age individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:

  • Individualized education plan (IEP) services:
    • An IEP provides specially designed instruction and related services to children who qualify.
    • IEP services will be reviewed annually to determine whether any changes are needed.
    • Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.
    • Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
    • PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
    • As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
  • A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
  • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
  • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 7 are recommended.

Table 7.

Recommended Surveillance for Individuals with SCARB2-Related Action Myoclonus – Renal Failure Syndrome

System/ConcernEvaluationFrequency
Myoclonus Severity of myoclonus using UMRSAt least annually
Seizures Seizure type & frequency
Cerebellar involvement Clinical evalPer symptom progression
Sensorimotor nerve involvement EMG, neurologic examAs needed based on clinical findings
Hearing Audiogram & BAEPAnnually
Dysarthria Assess need for alternative communication method or speech therapy.Per symptom progression
Dysphagia Assess aspiration risk & feeding methods.
Weight /
Nutritional status
  • Monitor BMI.
  • Consult a nutritionist.
  • High-calorie supplementation
ADL Clinical assessment to evaluate rehab planAt least annually
School performance Interview
Cognitive/
Psychiatric 		Evaluate mood, signs of psychosis, & cognitive complaints to identify need for pharmacologic & psychotherapeutic interventions.Per symptom progression & development of psychiatric symptoms
Renal involvement For those w/known renal disease:
  • Urine protein/creatinine
  • Nephrology follow up
Per treating nephrologist
For those w/o known renal disease:
  • Measurement of blood pressure
  • Urine protein/creatinine
  • Serum creatinine concentration
Annually
Family/Community Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).At each visit

ADL = activities of daily living; BAEP = brain stem auditory evoked potentials; EMG = electromyogram; UMRS = Unified Myoclonus Rating Scale

Agents/Circumstances to Avoid

Phenytoin may aggravate neurologic symptoms or even accelerate cerebellar degeneration.

Sodium channel blockers (carbamazepine, oxcarbazepine), GABAergic drugs (tiagabine, vigabatrin), and gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures [Mantoan & Walker 2011].

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 (ASMs) can increase the risk of malformations, growth restriction, or neurodevelopmental disabilities in exposed fetuses. However, when pregnant women experience prolonged seizures, the risk of adverse fetal outcomes is increased. Therefore, it is recommended that pregnant women with a known seizure disorder continue to take ASMs and the prescribing physician follows standard measures to prevent fetopathy, including:

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

In addition, all women of childbearing age should be advised to take 1 mg/day of folic acid and increase it to 4 mg/day when planning a pregnancy (ideally three months prior to conception) and during the pregnancy, in order to reduce the risk of neural tube defects and other congenital malformations that can be associated with fetal exposure to ASMs.

See MotherToBaby for further information on medication use during pregnancy.

Therapies Under Investigation

Substrate reduction therapy (SRT) with miglustat (600 mg daily) has been reported to improve myoclonus, epilepsy, and dysphagia [Chaves et al 2011, Quraishi et al 2021].

While venglustat theoretically has a similar mechanism of action with better central nervous system penetration than miglustat, no reports of its use in SCARB2-AMRF have been published to date.

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

SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected individual are presumed to be heterozygous for a SCARB2 pathogenic variant.
  • Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a SCARB2 pathogenic variant and to allow reliable recurrence risk assessment.
  • If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a de novo event in the proband or as a postzygotic de novo event in a mosaic parent [Jónsson et al 2017]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:
    • A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;
    • Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

  • If both parents are known to be heterozygous for a SCARB2 pathogenic variant, each sib of an affected individual has at conception 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.
  • The number and range of clinical manifestations and the order of their appearance can vary between affected sibs. Neurologic manifestations may occur first or in isolation in some family members, and renal manifestations may occur first or in isolation in other family members [Badhwar et al 2004].
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband. Unless an affected individual's reproductive partner also has SCARB2-AMRF or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in SCARB2.

Other family members. Each sib of the proband's parents is at 50% risk of being a carrier of a SCARB2 pathogenic variant.

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

  • For women who are affected with SCARB2-AMRF and considering pregnancy, standard measures for prevention of fetopathy should be followed (see Pregnancy Management).
  • The optimal time for determination of genetic risk 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 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 and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

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; 866-748-8008
  • 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 of Canada
    Canada
    Phone: 514-369-4806
    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.

SCARB2-Related 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 SCARB2-Related 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

Molecular Pathogenesis

SCARB2 encodes lysosome membrane protein 2 (LMP2), a lysosomal membrane protein necessary for proper sorting, retention, and targeting of the enzyme beta-glucocerebrosidase (GC). GC binds to LIMP2 early in the endoplasmic reticulum secretory pathway and is targeted into the lysosome in a manner independent from the mannose-6-phosphate receptor pathway [Reczek et al 2007]. GC is required for lysosomal hydrolysis of glucosylceramide and is implicated in Gaucher disease. Pathogenic variants in SCARB2 result in missorting and depletion of GC in lysosomes. As neurologic phenotypes are associated with pathogenic GBA (which encodes GC) variants in both the homozygous and heterozygous states, this is thought to be one of the drivers of SCARB2-related action myoclonus – renal failure syndrome (SCARB2-AMRF) pathogenesis.

LMP2 likely also has other less well-characterized functions possibly related to cholesterol transport that may also contribute to disease pathogenesis [Heybrock et al 2019].

Mechanism of disease causation. Loss-of-function variants or variants that lead to abnormal localization of LMP2 lead to SCARB2-AMRF.

Table 8.

Notable SCARB2 Pathogenic Variants

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeComment [Reference]
NM_005506​.4
NP_005497​.1 		c.862C>Tp.Gln288TerIn the French Canadian population, the vast majority of probands are homozygous for this variant [Dibbens et al 2011].
NM_005506​.4 c.1187+2dupT--In the French Canadian population, a small proportion of probands are compound heterozygotes for this variant & c.862C>T [Dibbens et al 2011].
NM_005506​.4
NP_005497​.1 		c.1385_1390delGATCCAinsATGCATGCACCp.Gly462AspfsTer34Homozygosity for this variant was reported in 2 Japanese families w/late-onset disease [Higashiyama et al 2013, Fu et al 2014].

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.

Chapter Notes

Author Notes

Dr Changrui Xiao (ude.icu.sh@xrgnahc), Dr Camilo Toro (vog.hin.liam@corot), and Dr Sara Kibrom (ude.drofnats@morbiks) would be happy to communicate with persons who have any questions regarding the diagnosis of SCARB2-related action myoclonus – renal failure syndrome or other considerations.

Acknowledgments

This work was supported by funds from the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Author History

Dina Amrom, MD; McGill University (2015-2023)
Eva Andermann, MDCM, PhD, FCCMG; McGill University (2015-2023)
Frederick Andermann, MD, FRCP(C); McGill University (2015-2023)
Haejun Ahn, MD (2023-present)
Sara Kibrom, MD (2023-present)
Camilo Toro, MD (2023-present)
Changrui Xiao, MD (2023-present)

Revision History

  • 9 February 2023 (bp) Comprehensive update posted live
  • 17 December 2015 (me) Review posted live
  • 25 February 2014 (da) Original submission

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