Synonyms: Dystonia 11, Hereditary Essential Myoclonus, Myoclonic Dystonia

Raymond D, Ozelius L.

Publication Details


Clinical characteristics.

Myoclonus-dystonia (M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus) and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). The myoclonic jerks typical of M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Non-motor features may include obsessive-compulsive disorder (OCD), depression, anxiety, personality disorders, alcohol abuse, and panic attacks. Symptom onset is usually in childhood or early adolescence but ranges from age six months to 80 years. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. M-D is compatible with an active life of normal span.


The diagnosis of myoclonus-dystonia is based on clinical findings, family history, absence of other neurologic deficits, and normal neuroimaging studies. Pathogenic variants in SGCE are associated with most cases of familial M-D. Pathogenic variants in two other genes, DRD2 and DYT1, have been associated with M-D as well; the significance of these variants is unknown. Molecular testing includes both sequence and deletion/duplication analyses of the coding region of SGCE.


Treatment of manifestations: Benzodiazepines (particularly clonazepam) used to treat myoclonus-dystonia improve both myoclonus and tremor. Antiepileptic drugs (valproate, topiramate) may improve myoclonus, but the response is variable. Anticholinergic medication may improve dystonia; botulinum toxin injection may be especially helpful for cervical dystonia. Improvement with L-5-hydroxytryptophan, L-dopa and the salt of sodium oxybate has been reported. Stereotactic thalamotomy can improve myoclonus but has caused dysarthria and hemiparesis. Deep brain stimulation has improved both myoclonus and dystonia in several individuals; it is unclear whether targeting the globus pallidus interna (GPi) is more effective than targeting the ventral intermediate nucleus of the thalamus (VIM).

Other: Symptoms of M-D often improve short term with ingestion of alcohol, but the risk of addiction recommends against its long term use.

Genetic counseling.

Myoclonus-dystonia is inherited in an autosomal dominant manner. A proband with M-D may have inherited the disorder from a parent or have it as the result of a de novo pathogenic variant; the proportion of cases caused by de novo variants is unknown. Each child of an individual with M-D has a 50% chance of inheriting the pathogenic variant. In general, maternally derived SGCE alleles are not expressed and paternally derived SGCE alleles are expressed. Thus, almost all children who inherit an SGCE pathogenic variant from their father develop symptoms, whereas close to 95% of children who inherit an SGCE pathogenic variant from their mother do not. Prenatal testing and preimplantation genetic diagnosis are possible for families in which the pathogenic variant is known.


Clinical Diagnosis

The following diagnostic criteria for myoclonus-dystonia (M-D), modified from Mahloudji & Pikielny [1967] and Gasser [1998], were proposed by Klein [2002] based on families with proven linkage to DYT11 or an SGCE pathogenic variant.

  • Onset of myoclonus, usually in the first or second decade of life; dystonic features are also observed in more than half of affected individuals in addition to myoclonus; rarely, dystonia may be the only manifestation of the disorder.
  • Males and females about equally affected
  • A relatively benign course, often variable but compatible with an active life of normal span in most cases
  • Autosomal dominant mode of inheritance with variable severity and incomplete penetrance, which is dependent on the parental origin of the disease allele; in most cases a symptomatic individual inherits the pathogenic variant from his/her father.
  • Absence of dementia, gross ataxia, and other neurologic deficits
  • Normal somatosensory evoked potentials (SSEP)
  • Normal neuroimaging studies (CT or MRI). Note: Degenerative changes may be seen as a result of chronic alcohol use.

Optional diagnostic criteria:

  • Alleviation of symptoms (particularly of the myoclonus and to a lesser degree of the dystonia) with alcohol use
  • Various psychiatric symptoms

Note: Normal EEG was a diagnostic criterion; however, two reports have associated genetically confirmed familial M-D with epilepsy and/or EEG abnormalities [Foncke et al 2003, O'Riordan et al 2004]. Therefore, EEG changes and epilepsy should no longer be considered exclusion criteria.


In general, all laboratory tests are normal in individuals with M-D. Abnormal liver function tests may be the result of chronic alcohol use.

Molecular Genetic Testing

Genes. SGCE (locus DYT11), encoding the protein epsilon-sarcoglycan, is the only gene in which pathogenic variants are known to cause M-D.

Evidence for locus heterogeneity. An SGCE pathogenic variant or deletion is detected in approximately 30%-40% of persons having the typical M-D phenotype (see Table 1).

Simplex and familial cases without identifiable SGCE pathogenic variants have been reported [Han et al 2003, Valente et al 2003, Grundmann et al 2004, Hedrich et al 2004, Schüle et al 2004, Valente et al 2005, Tezenas du Montcel et al 2006, Grünewald et al 2008, Ritz et al 2009], suggesting locus heterogeneity.

Pathogenic variants in two other genes have been associated with M-D in a few individuals/families.

  • DRD2. It is unclear if the DRD2 missense variant found in a single family is disease-causing, disease-modifying, or a rare polymorphism [Klein et al 1999], as further analysis in this family also identified a 5-bp deletion in SGCE (c.835_839delACAAA) [Klein et al 2002].
  • DYT1, the gene associated with early-onset primary dystonia (DYT1):
    • An 18-bp deletion in DYT1 was found in one family [Leung et al 2001]. However, a p.Leu196Arg missense SGCE variant was subsequently identified [Klein et al 2002]; the significance of the combination of these two variants is unknown.
    • A male with alcohol-responsive M-D who had the typical three-base pair deletion in DYT1 and no pathogenic variant in SGCE was reported [Tezenas du Montcel et al 2006]. His mother was Ashkenazi Jewish but only had writer's cramp.
  • Maternal uniparental disomy (mUPD) of chromosome 7. Two persons with M-D and Russell-Silver syndrome (RSS) associated with mUPD of chromosome 7 have been reported.
    • Patient 1. Only maternal chromosome 7 markers were present; both SGCE alleles were methylated; and SGCE expression was absent. The RSS phenotype in this individual is presumably attributable to mUPD of another imprinted gene on chromosome 7 [Guettard et al 2008].
    • Patient 2. An atypical RSS phenotype was accompanied by myoclonus. Maternal iso/heterodisomy of chromosome 7 was present and may account for the atypical presentation [Stark et al 2010].
  • DYT15 locus. A clinically similar M-D phenotype in a large Canadian family without an identifiable SGCE pathogenic variant showed significant evidence for linkage to markers on chromosome 18p (locus DYT15) [Grimes et al 2002, Han et al 2007]. The M-D phenotype of two other families may also be linked to this chromosomal region [Schüle et al 2004]. The overall contribution of this locus to M-D cannot be determined until the gene is identified.
Table 1.

Table 1.

Summary of Molecular Genetic Testing Used in Myoclonus-Dystonia

Testing Strategy

To establish the diagnosis in a proband

  • The diagnosis of myoclonus-dystonia is made clinically.
  • Molecular genetic testing of SGCE may be helpful for clarifying an equivocal diagnosis and for genetic counseling purposes.
    • Sequence analysis is performed first.
    • If a pathogenic variant is not identified, deletion/duplication analysis is considered.

Testing for at-risk asymptomatic adult family members requires prior identification of the pathogenic variant in the family.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variant in the family.

Clinical Characteristics

Clinical Description

Myoclonus-dystonia (M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus), and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). Onset usually occurs in childhood or early adolescence, particularly in families with an SGCE pathogenic variant, but ranges from six months to more than 80 years for all M-D whether or not a causative variant has been identified [Foncke et al 2006, Gerrits et al 2006, Tezenas du Montcel et al 2006, Nardocci et al 2008, Raymond et al 2008, Ritz et al 2009].

Although most affected adults report a dramatic response of myoclonus to alcohol ingestion [Mahloudji & Pikielny 1967, Kyllerman et al 1990, Quinn 1996], the alleviation of findings following alcohol ingestion varies within and between families

The myoclonic jerks typical of M-D are brief, lightning-like movements most often affecting the neck, trunk, and upper limbs with legs affected less prominently. Myoclonus is usually the presenting manifestation of M-D. Laryngeal myoclonus has been reported [Hjermind et al 2003].

Approximately half of affected individuals (54%) have focal or segmental dystonia that manifests as cervical dystonia and/or writer's cramp [Asmus et al 2002, Klein 2002]. In contrast to primary torsion dystonia [Bressman et al 2000], involvement of lower limbs is rare and usually does not occur at onset. In addition, the dystonia does not tend to worsen or generalize in the course of the disease. Rarely, dystonia is the only disease manifestation.

The involuntary movements are frequently precipitated or worsened by active movements of the affected body parts. Other factors eliciting or enhancing the movements include stress [Korten et al 1974, Kyllerman et al 1990], sudden noise [Korten et al 1974, Kurlan et al 1988, Asmus et al 2001, Trottenberg et al 2001], caffeine [Nygaard et al 1999], and tactile stimuli [Kurlan et al 1988, Nygaard et al 1999].

Additional neurologic features mainly include postural and other forms of tremor [Korten et al 1974, Kurlan et al 1988, Kyllerman et al 1990, Vidailhet et al 2001].

The most prominent non-motor features have been psychiatric disease reported in some [Kyllerman et al 1990, Klein et al 1999, Nygaard et al 1999], but not all families [Asmus et al 2001]. However, systematic study for psychiatric illness was not performed in these families with M-D and it is unknown whether these features segregated with the M-D-causing pathogenic variant. Reported psychiatric problems include:

Saunders-Pullman et al [2002a] studied psychiatric features in detail in three families linked to chromosome 7q and found an association between OCD and M-D. This finding was supported by Doheny et al [2002] and Maréchal et al [2003] and was confirmed in genetically confirmed cases by Hess et al [2007], who reported OCD in combination with M-D in several other families.

Other neurologic signs and symptoms including dementia and ataxia are rare in M-D [Gasser 1998]. Seizures have been reported in two families, but the significance of this finding remains unclear [Foncke et al 2003, O'Riordan et al 2004].

M-D is compatible with an active life of normal span [Nygaard et al 1999].

Although spontaneous remission of M-D has been reported [Korten et al 1974, Fahn & Sjaastad 1991, Roze et al 2008], in some cases M-D may be gradually progressive [Kurlan et al 1988, Quinn 1996, Borges et al 2000, Trottenberg et al 2001] and may lead to considerable functional disability and result in early retirement [Borges et al 2000, Trottenberg et al 2001, Hjermind et al 2003, Maréchal et al 2003].

Neurophysiology and Neuroimaging

Neurophysiologic studies in persons with M-D, including routine electroencephalography (EEG), polymyography, and somatosensory evoked potentials (SEPs), were normal [Chokroverty et al 1987, Quinn et al 1988].

Roze et al [2008] noted short jerks of subcortical origin in persons with M-D while at rest, with activity, or while standing.

Marelli et al [2008] found neurophysiologic signs suggesting the dysfunction of systems including brain stem and neocortex.

Li et al [2008] identified normal intracortical inhibition in persons with M-D with dystonia and suggested that the role of cortical dysfunction may be less prominent and that the mechanisms for dystonia in M-D may be different from those in other dystonic disorders.

Another neurophysiologic study showed that globus pallidus interna (GPi) deep brain stimulation (DBS) resulted in substantial decrease in the frequency and amplitude of myoclonus and suppression of dystonia, suggesting that in M-D the pallidum plays a role in generation, or at least modulation, of both these hyperkinetic features [Kurtis et al 2010].

Functional MRI studies support subcortical activation [Nitschke et al 2006]:

  • In an 18F-FDG PET performed on an individual with genetically confirmed M-D, Tai et al [2009] noted significant bilateral hypermetabolism in the thalamus and cerebellum.
  • Functional MRI in a five-year old girl with genetically confirmed M-D revealed specific activations within the thalamus and dentate nucleus [Nitschke et al 2006]. Reduced striatal D2 receptor binding in M-D has been demonstrated [Beukers et al 2009] as well as frontotemporal and striatal SPECT abnormalities [Papapetropoulos et al 2008].

Genotype-Phenotype Correlations

No genotype-phenotype correlations for SGCE are known.


Reduced penetrance on maternal transmission of the disease allele has been observed, suggesting that maternal genomic imprinting of SGCE suppresses expression of the maternally inherited SGCE allele [Zimprich et al 2001].

  • Consistent with this hypothesis, two studies demonstrated both paternal transmission of the SGCE mutant allele in affected individuals and DNA methylation differences consistent with maternal imprinting [Müller et al 2002, Grabowski et al 2003].
  • Because about 5% of affected individuals inherit the mutant allele from their mothers [Zimprich et al 2001, Grabowski et al 2003], the apparent suppression of the M-D phenotype on maternal transmission of the SGCE allele is incomplete. In these instances, the phenotype may be milder. The reasons for loss of the maternal imprint are unknown.


Anticipation is not observed in M-D.


Terms used in the past for myoclonus-dystonia include myoclonic dystonia, inherited myoclonus dystonia syndrome, alcohol-responsive myoclonic dystonia, hereditary essential myoclonus, and DYT11 dystonia [Quinn et al 1988, Quinn 1996, Lang 1997, Saunders-Pullman et al 2002b].

When myoclonic movements were reported in individuals with DYT1 or other forms of primary dystonia, it was called myoclonic dystonia syndrome [Obeso et al 1983].


Little is known about the prevalence of M-D; however, the disease has been described in families of many nationalities including mixed European, German, Irish, Turkish, Brazilian, and Canadian.

Differential Diagnosis

Familial conditions with dystonia, including Wilson disease, spinocerebellar ataxia type 3 (SCA3), ataxia with vitamin E deficiency and other secondary forms of dystonia, can generally be differentiated from M-D based on laboratory tests and neuroimaging studies (including MRI) (for a review of various genetic and secondary forms of dystonia, see Dystonia Overview and de Carvalho Aguiar & Ozelius [2002]).

One individual with genetically confirmed dopa-responsive dystonia [Leuzzi et al 2002] and one with genetically confirmed spinocerebellar ataxia type 14 (SCA14) [Foncke et al 2010] presented with findings of myoclonus dystonia.

Most other conditions in which myoclonus is a prominent feature are characterized by a variety of neurologic signs and symptoms that generally are not associated with a diagnosis of M-D. Genetic disorders with myoclonus as a major component include the following:

The findings in benign hereditary chorea (BHC) caused by pathogenic variants in NKX2-1 may be somewhat similar to those in M-D; however, in contrast to the action induced myoclonus of M-D, BHC does not demonstrate aggravation of jerks with complex motor tasks. Because of the association of hypothyroidism with pathogenic variants in this gene, thyroid hormone screening should be considered in affected individuals. See OMIM 118700, 610978, 600635.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with myoclonus-dystonia (M-D) the following evaluations are recommended:

  • Clinical examination to evaluate the location, severity, and progression of dystonia and the severity and progression of myoclonus. This is best done by a neurologic specialist in movement disorders.
  • MRI
  • Clinical genetics consultation

Treatment of Manifestations

Medications may improve either the myoclonus or the dystonia or both:

Note: Although the symptoms of M-D usually resolve with ingestion of alcohol, the risk of long-term addiction to alcohol renders it an unacceptable treatment option.

Surgery. Stereotactic thalamotomy can improve myoclonus, but caused dysarthria in one individual and mild hemiparesis in another [Gasser et al 1996]. In two others, myoclonus improved, but without significant gain in function [Suchowersky et al 2000].

Deep brain stimulation (DBS). In a recent study, ten persons with M-D (9 with an identifiable SGCE pathogenic variant) had DBS of the internal segment of the globus pallidus (GPi) only (1 person), of the ventral intermediate thalamic nucleus (VIM) only, or of both GPi and VIM (8 persons). All experienced substantial improvement of both myoclonus (61.5%) and dystonia (48.2%). No adverse effects on cognition or affect were noted. VIM DBS was associated with a slightly higher incidence of reversible adverse events, possibly accounting for the slightly less robust improvement noted in those treated with VIM vs GPi DBS. The authors also note that quadruple VIM/GPi stimulation may be slightly more effective than VIM or GPi alone [Gruber et al 2010].

The results of case studies are summarized below:

  • Improvement of M-D was reported in a 63-year old with symptoms from age two years, suggesting that the findings are responsive to DBS, even after more than 50 years [Kurtis et al 2010].
  • Neurostimulation of the ventral intermediate thalamic nucleus (VIM) in an individual with medically intractable and progressive inherited M-D resulted in an 80% reduction of myoclonus score, but no significant effect on dystonia. A second individual who had genetically confirmed M-D had a 14% reduction of myoclonus score following VIM stimulation [Trottenberg et al 2001, Kuncel et al 2009].
  • DBS of the internal segment of the globus pallidus (GPi) improved myoclonus and dystonia in two individuals [Cif et al 2004, Magariños-Ascone et al 2005], one of whom had a confirmed SGCE pathogenic variant [Cif et al 2004].
  • DBS of the medial globus pallidus improved both myoclonus and dystonia at an eight-week follow-up [Liu et al 2002].

Prevention of Secondary Complications

As self-treatment with alcohol is common, proper treatment and counseling regarding alcohol abuse may decrease alcohol-related toxicities, particularly in adolescents.

Evaluation of Relatives at Risk

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

Therapies Under Investigation

Search for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, 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. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Myoclonus-dystonia is inherited in an autosomal dominant manner with reduced penetrance. Penetrance is related to maternal imprinting and, therefore, is based on the parental origin of the pathogenic variant. In general, maternally derived SGCE alleles are not expressed and paternally derived SGCE alleles are expressed.

Risk to Family Members

Parents of a proband

  • Some individuals diagnosed with M-D have an affected parent.
  • Because M-D shows reduced penetrance, the parent of an affected individual may have the pathogenic allele without showing clinical signs. The mechanism of reduced penetrance is related to maternal imprinting and, therefore, based on the parental origin of the pathogenic variant. In general, maternal imprinting suppresses expression of a maternally derived SGCE allele, whether it is normal or has a pathogenic variant. Paternally derived SGCE alleles are expressed.
    • More than 95% of individuals who inherit the pathogenic allele from their mothers do not have clinical signs. Approximately 5% of individuals who inherit the pathogenic allele from their mothers do develop M-D. This indicates that the apparent suppression of the phenotype by maternal inheritance of a pathogenic SGCE allele is incomplete; it appears that loss of the maternal imprint occurs at a low frequency.
    • As expected, the majority of individuals who inherit the pathogenic allele from their fathers have clinical symptoms. In addition, persons who were initially thought to be simplex cases (i.e., a single occurrence of M-D in their family) have been shown to have an SGCE pathogenic variant that was inherited from an asymptomatic father [Müller et al 2002, Hedrich et al 2004, Kock et al 2004, Gerrits et al 2009].
  • A proband with M-D may have the disorder as the result of a de novo SGCE pathogenic variant [Hedrich et al 2004]; the proportion of cases caused by de novo pathogenic variants is unknown.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo pathogenic variant include obtaining a detailed medical and family history, examination by a neurologist specializing in movement disorders, and molecular genetic testing if the family-specific SGCE variant has been identified.

Sibs of a proband

  • The risk to the sib of a proband depends on the genetic status of the parents.
  • If a parent of the proband is affected, the risk to the sibs of inheriting the pathogenic allele is 50%.
  • Expression of the pathogenic SGCE allele is influenced by the sex of the parent transmitting the allele (imprinting).
    • If the SGCE pathogenic allele is inherited from the father, it is typically expressed and most often the offspring is symptomatic.
    • If the SGCE pathogenic allele is inherited from the mother, most often it is not expressed and the child remains symptom-free. However, about 5% of individuals who inherit the pathogenic variant from their mothers do develop symptoms. These symptoms may be milder than those in individuals who inherit the variant from their fathers.
  • Because of variable expressivity, sibs may be more or less severely affected with findings different from those of the proband.
  • If a pathogenic variant cannot be detected in the DNA of either parent, two possible explanations are germline mosaicism in a parent or a de novo pathogenic variant in the proband. Although no instances of germline mosaicism have been reported, it remains a possibility.

Offspring of a proband

  • Each child of an individual with M-D has a 50% chance of inheriting the pathogenic variant.
  • Almost all children who inherit the pathogenic variant from their fathers develop symptoms.
  • About 5% of children who inherit the pathogenic variant from their mothers develop symptoms.
  • Symptomatic offspring of a proband may be more or less severely affected than the proband.

Other family members of a proband. The risk to other family members depends on the genetic status of the proband's parents: if a parent is affected or has a pathogenic allele, his or her family members are at risk.

Related Genetic Counseling Issues

Although most individuals diagnosed with M-D have inherited the pathogenic allele from a parent, the family history may appear to be negative either because of the effects of imprinting or because of failure to recognize the disorder in family members. Since it is possible for affected family members to self-medicate with alcohol, a family history of alcoholism may be indicative of additional affected relatives.

Non-medical considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with an autosomal dominant condition has a pathogenic variant or clinical evidence of the disorder, it is likely that the proband has a de novo pathogenic variant. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Testing of at-risk asymptomatic family members. Testing of at-risk asymptomatic family members for myoclonus-dystonia is possible using the techniques described in Molecular Genetic Testing. Such testing is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals. However, adults are unlikely to become symptomatic, particularly when inheriting the gene through a mother. When testing at-risk individuals for myoclonus-dystonia, an affected family member should be tested first to confirm the molecular diagnosis in the family.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal 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 or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the pathogenic variant has been identified in an affected family member, prenatal diagnosis for a pregnancy at increased risk and preimplantation genetic diagnosis are possible options.


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.

  • Dystonia Medical Research Foundation
    One East Wacker Drive
    Suite 2810
    Chicago IL 60601-1905
    Phone: 800-377-3978 (toll-free); 312-755-0198
    Fax: 312-803-0138
  • Dystonia Society
    89 Albert Embankment
    3rd Floor
    London SE1 7TP
    United Kingdom
    Phone: 0845 458 6211; 0845 458 6322 (Helpline)
    Fax: 0845 458 6311
  • National Institute of Neurological Disorders and Stroke (NINDS)
    PO Box 5801
    Bethesda MD 20824
    Phone: 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)
  • Global Dystonia Registry

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.

Table A.

Myoclonus-Dystonia: Genes and Databases

Table B.

Table B.

OMIM Entries for Myoclonus-Dystonia (View All in OMIM)

Gene structure. SGCE comprises 12 exons with exon 10 being differentially spliced and absent from most transcripts [McNally et al 1998]. Other alternative splice variants in mouse brain that affect the C-terminal end of the encoded protein have been identified [Nishiyama et al 2004, Yokoi et al 2005]. See Table A, Gene for a detailed summary of gene and protein information.

Pathogenic allelic variants. All types of variants have been reported in SGCE: nonsense and missense variants, deletions, and insertions leading to frame shifts and splicing errors [Zimprich et al 2001, Asmus et al 2002, Doheny et al 2002, Klein et al 2002, Müller et al 2002, DeBerardinis et al 2003, Foncke et al 2003, Han et al 2003, Hjermind et al 2003, Maréchal et al 2003, Hedrich et al 2004, Kock et al 2004, Schüle et al 2004, Valente et al 2005].

Exon deletions in SGCE may also cause M-D [Asmus et al 2005].

Most of the pathogenic variants described to date have been localized to exons 3-7 and 9, implicating this region of the gene as important for function. Four nonsense variants, p.Arg97Ter, p.Trp100Ter, p.Arg102Ter (all in exon 3), and p.Arg372Ter (in exon 9) as well as two small deletions (in exons 4 and 7) [Grünewald et al 2008] have been found in more than one proband and appear to be recurrent variants. (For more information, see Table A.)

Table 2.

Table 2.

Selected SGCE Pathogenic Variants

See Table 3 (pdf) for a summary of all pathogenic variants known to date.

Normal gene product. SGCE encodes epsilon-sarcoglycan. SGCE is a member of a gene family that also includes alpha, beta, gamma, delta, and zeta sarcoglycans. Recessive pathogenic variants in these other sarcoglycan family members result in various types of limb-girdle muscular dystrophies (see Hack et al [2000] for review). In muscles, these genes encode transmembrane components of the dystrophin-glycoprotein complex, which link the cytoskeleton to the extracellular matrix. However, SGCE is widely expressed in many tissues of the body [Ettinger et al 1997, McNally et al 1998] including various regions of the brain [Zimprich et al 2001, Xiao & LeDoux 2003, Nishiyama et al 2004, Chan et al 2005] both during development and adulthood. The function of epsilon-sarcoglycan in the brain is unknown.

Abnormal gene product. It is speculated that because maternal imprinting transcriptionally silences SGCE and the vast majority of affected individuals inherit their disease allele from their fathers, the disease is caused by loss of function of this protein. However, about 5% of affected individuals inherit their mutated allele from their mothers and presumably also express the wild-type allele from their fathers. Therefore, the mechanism of disease pathogenesis is not entirely clear.


Literature Cited

  • Asmus F, Hjermind LE, Dupont E, Wagenstaller J, Haberlandt E, Munz M, Strom TM, Gasser T. Genomic deletion size at the epsilon-sarcoglycan locus determines the clinical phenotype. Brain. 2007;130:2736–45. [PubMed: 17898012]

  • Asmus F, Salih F, Hjermind LE, Ostergaard K, Munz M, Kühn AA, Dupont E, Kupsch A, Gasser T. Myoclonus-dystonia due to genomic deletions in the epsilon-sarcoglycan gene. Ann Neurol. 2005;58:792–7. [PubMed: 16240355]

  • Asmus F, Zimprich A, Naumann M, Berg D, Bertram M, Ceballos-Baumann A, Pruszak-Seel R, Kabus C, Dichgans M, Fuchs S, Muller-Myhsok B, Gasser T. Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families. Ann Neurol. 2001;49:121–4. [PubMed: 11198282]

  • Asmus F, Zimprich A, Tezenas Du Montcel S, Kabus C, Deuschl G, Kupsch A, Ziemann U, Castro M, Kuhn AA, Strom TM, Vidailhet M, Bhatia KP, Durr A, Wood NW, Brice A, Gasser T. Myoclonus-dystonia syndrome: epsilon-sarcoglycan mutations and phenotype. Ann Neurol. 2002;52:489–92. [PubMed: 12325078]

  • Berardelli A, Curra A. Pathophysiology and treatment of cranial dystonia. Mov Disord. 2002;17 Suppl 2:S70–4. [PubMed: 11836760]

  • Beukers RJ, Booij J, Weisscher N, Zijlstra F, van Amelsvoort TA, Tijssen MA. Reduced striatal D2 receptor binding in myoclonus-dystonia. Eur J Nucl Med Mol Imaging. 2009;36:269–74. [PubMed: 18719906]

  • Bonnet C, Grégoire MJ, Vibert M, Raffo E, Leheup B, Jonveaux P. Cryptic 7q21 and 9p23 deletions in a patient with apparently balanced de novo reciprocal translocation t(7;9)(q21;p23) associated with a dystonia-plus syndrome: paternal deletion of the epsilon-sarcoglycan (SGCE) gene. J Hum Genet. 2008;53:876–85. [PubMed: 18651096]

  • Borges V, Ferraz HB, de Andrade LA. Alcohol-sensitive hereditary essential myoclonus with dystonia: a study of 6 Brazilian patients. Neurol Sci. 2000;21:373–7. [PubMed: 11441575]

  • Bressman SB, Greene PE. Treatment of hyperkinetic movement disorders. Neurol Clin. 1990;8:51–75. [PubMed: 2181268]

  • Bressman SB, Greene PE. Dystonia. Curr Treat Options Neurol. 2000;2:275–285. [PubMed: 11096754]

  • Bressman SB, Sabatti C, Raymond D, de Leon D, Klein C, Kramer PL, Brin MF, Fahn S, Breakefield X, Ozelius LJ, Risch NJ. The DYT1 phenotype and guidelines for diagnostic testing. Neurology. 2000;54:1746–52. [PubMed: 10802779]

  • Chan P, Gonzalez-Maeso J, Ruf F, Bishop DF, Hof PR, Sealfon SC. Epsilon-sarcoglycan immunoreactivity and mRNA expression in mouse brain. J Comp Neurol. 2005;482:50–73. [PubMed: 15612018]

  • Chokroverty S, Manocha MK, Duvoisin RC. A physiologic and pharmacologic study in anticholinergic-responsive essential myoclonus. Neurology. 1987;37:608–15. [PubMed: 3561772]

  • Cif L, Valente EM, Hemm S, Coubes C, Vayssiere N, Serrat S, Di Giorgio A, Coubes P. Deep brain stimulation in myoclonus-dystonia syndrome. Mov Disord. 2004;19:724–7. [PubMed: 15197720]

  • de Carvalho Aguiar PM, Ozelius LJ. Classification and genetics of dystonia. Lancet Neurol. 2002;1:316–25. [PubMed: 12849429]

  • DeBerardinis RJ, Conforto D, Russell K, Kaplan J, Kollros PR, Zackai EH, Emanuel BS. Myoclonus in a patient with a deletion of the epsilon-sarcoglycan locus on chromosome 7q21. Am J Med Genet. 2003;121A:31–6. [PubMed: 12900898]

  • Doheny DO, Brin MF, Morrison CE, Smith CJ, Walker RH, Abbasi S, Muller B, Garrels J, Liu L, De Carvalho Aguiar P, Schilling K, Kramer P, De Leon D, Raymond D, Saunders-Pullman R, Klein C, Bressman SB, Schmand B, Tijssen MA, Ozelius LJ, Silverman JM. Phenotypic features of myoclonus-dystonia in three kindreds. Neurology. 2002;59:1187–96. [PubMed: 12391346]

  • Ettinger AJ, Feng G, Sanes JR. Epsilon-sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D. J Biol Chem. 1997;272:32534–8. [PubMed: 9405466]

  • Fahn S, Sjaastad O. Hereditary essential myoclonus in a large Norwegian family. Mov Disord. 1991;6:237–47. [PubMed: 1922129]

  • Foncke EM, Beukers RJ, Tijssen CC, Koelman JH, Tijssen MA. Myoclonus-dystonia and spinocerebellar ataxia type 14 presenting with similar phenotypes: trunk tremor, myoclonus, and dystonia. Parkinsonism Relat Disord. 2010;16:288–9. [PubMed: 19913450]

  • Foncke EM, Gerrits MC, van Ruissen F, Baas F, Hedrich K, Tijssen CC, Klein C, Tijssen MA. Distal myoclonus and late onset in a large Dutch family with myoclonus-dystonia. Neurology. 2006;67:1677–80. [PubMed: 17101905]

  • Foncke EM, Klein C, Koelman JH, Kramer PL, Schilling K, Muller B, Garrels J, de Carvalho Aguiar P, Liu L, de Froe A, Speelman JD, Ozelius LJ, Tijssen MA. Hereditary myoclonus-dystonia associated with epilepsy. Neurology. 2003;60:1988–90. [PubMed: 12821748]

  • Frucht SJ, Bordelon Y, Houghton WH, Reardan D. A pilot tolerability and efficacy trial of sodium oxybate in ethanol-responsive movement disorders. Mov Disord. 2005;20:1330–7. [PubMed: 15986420]

  • Ganesh S, Delgado-Escueta AV, Suzuki T, Francheschetti S, Riggio C, Avanzini G, Rabinowicz A, Bohlega S, Bailey J, Alonso ME, Rasmussen A, Thomson AE, Ochoa A, Prado AJ, Medina MT, Yamakawa K. Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype. Hum Mol Genet. 2002;11:1263–71. [PubMed: 12019207]

  • Gasser T. Inherited myoclonus-dystonia syndrome. Adv Neurol. 1998;78:325–34. [PubMed: 9750929]

  • Gasser T, Bereznai B, Muller B, Pruszak-Seel R, Damrich R, Deuschl G, Oertel WH. Linkage studies in alcohol-responsive myoclonic dystonia. Mov Disord. 1996;11:363–70. [PubMed: 8813214]

  • Gerrits MC, Foncke EM, de Haan R, Hedrich K, van de Leemput YL, Baas F, Ozelius LJ, Speelman JD, Klein C, Tijssen MA. Phenotype-genotype correlation in Dutch patients with myoclonus-dystonia. Neurology. 2006;66:759–61. [PubMed: 16534121]

  • Gerrits MC, Foncke EM, Koelman JH, Tijssen MA. Pediatric writer's cramp in myoclonus-dystonia: maternal imprinting hides positive family history. Eur J Paediatr Neurol. 2009;13:178–80. [PubMed: 18571946]

  • Goetz CG, Horn SS. Treatment of tremor and dystonia. Neurol Clin. 2001;19:129–44. [PubMed: 11471761]

  • Grabowski M, Zimprich A, Lorenz-Depiereux B, Kalscheuer V, Asmus F, Gasser T, Meitinger T, Strom TM. The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted. Eur J Hum Genet. 2003;11:138–44. [PubMed: 12634861]

  • Grimes DA, Han F, Lang AE, St George-Hyssop P, Racacho L, Bulman DE. A novel locus for inherited myoclonus-dystonia on 18p11. Neurology. 2002;59:1183–6. [PubMed: 12391345]

  • Gruber D, Kühn AA, Schoenecker T, Kivi A, Trottenberg T, Hoffmann KT, Gharabaghi A, Kopp UA, Schneider GH, Klein C, Asmus F, Kupsch A. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord. 2010;25:1733–43. [PubMed: 20623686]

  • Grundmann K, Laubis-Herrmann U, Dressler D, Vollmer-Haase J, Bauer P, Stuhrmann M, Schulte T, Schols L, Topka H, Riess O. Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias. Mov Disord. 2004;19:1294–7. [PubMed: 15390016]

  • Grünewald A, Djarmati A, Lohmann-Hedrich K, Farrell K, Zeller JA, Allert N, Papengut F, Petersen B, Fung V, Sue CM, O'Sullivan D, Mahant N, Kupsch A, Chuang RS, Wiegers K, Pawlack H, Hagenah J, Ozelius LJ, Stephani U, Schuit R, Lang AE, Volkmann J, Münchau A, Klein C. Myoclonus-dystonia: significance of large SGCE deletions. Hum Mutat. 2008;29:331–2. [PubMed: 18205193]

  • Guettard E, Portnoi MF, Lohmann-Hedrich K, Keren B, Rossignol S, Winkler S, El Kamel I, Leu S, Apartis E, Vidailhet M, Klein C, Roze E. Myoclonus-dystonia due to maternal uniparental disomy. Arch Neurol. 2008;65:1380–5. [PubMed: 18852357]

  • Hack AA, Groh ME, McNally EM. Sarcoglycans in muscular dystrophy. Microsc Res Tech. 2000;48:167–80. [PubMed: 10679964]

  • Han F, Lang AE, Racacho L, Bulman DE, Grimes DA. Mutations in the epsilon-sarcoglycan gene found to be uncommon in seven myoclonus-dystonia families. Neurology. 2003;61:244–6. [PubMed: 12874409]

  • Han F, Racacho L, Lang AE, Bulman DE, Grimes DA. Refinement of the DYT15 locus in myoclonus dystonia. Mov Disord. 2007;22:888–92. [PubMed: 17274032]

  • Hedrich K, Meyer EM, Schule B, Kock N, de Carvalho Aguiar P, Wiegers K, Koelman JH, Garrels J, Durr R, Liu L, Schwinger E, Ozelius LJ, Landwehrmeyer B, Stoessl AJ, Tijssen MA, Klein C. Myoclonus-dystonia: detection of novel, recurrent, and de novo SGCE mutations. Neurology. 2004;62:1229–31. [PubMed: 15079037]

  • Hess CW, Raymond D, Aguiar Pde C, Frucht S, Shriberg J, Heiman GA, Kurlan R, Klein C, Bressman SB, Ozelius LJ, Saunders-Pullman R. Myoclonus-dystonia, obsessive-compulsive disorder, and alcohol dependence in SGCE mutation carriers. Neurology. 2007;68:522–4. [PubMed: 17296918]

  • Hjermind LE, Werdelin LM, Eiberg H, Krag-Olsen B, Dupont E, Sorensen SA. A novel mutation in the epsilon-sarcoglycan gene causing myoclonus-dystonia syndrome. Neurology. 2003;60:1536–9. [PubMed: 12743249]

  • Klein C. Myoclonus and myoclonus-dystonias. In: Pulst S, ed. Genetics of Movement Disorders. San Diego, CA: Academic Press; 2002:449-69.

  • Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ. Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. Proc Natl Acad Sci U S A. 1999;96:5173–6. [PMC free article: PMC21836] [PubMed: 10220438]

  • Klein C, Liu L, Doheny D, Kock N, Muller B, de Carvalho Aguiar P, Leung J, de Leon D, Bressman SB, Silverman J, Smith C, Danisi F, Morrison C, Walker RH, Velickovic M, Schwinger E, Kramer PL, Breakefield XO, Brin MF, Ozelius LJ. Epsilon-sarcoglycan mutations found in combination with other dystonia gene mutations. Ann Neurol. 2002;52:675–9. [PubMed: 12402271]

  • Kock N, Kasten M, Schule B, Hedrich K, Wiegers K, Kabakci K, Hagenah J, Pramstaller PP, Nitschke MF, Munchau A, Sperner J, Klein C. Clinical and genetic features of myoclonus-dystonia in 3 cases: a video presentation. Mov Disord. 2004;19:231–4. [PubMed: 14978685]

  • Korten JJ, Notermans SL, Frenken CW, Gabreels FJ, Joosten EM. Familial essential myoclonus. Brain. 1974;97:131–8. [PubMed: 4434166]

  • Kuncel AM, Turner DA, Ozelius LJ, Greene PE, Grill WM, Stacy MA. Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus-dystonia syndrome. Clin Neurol Neurosurg. 2009;111:303–6. [PMC free article: PMC3101371] [PubMed: 19081669]

  • Kurlan R, Behr J, Medved L, Shoulson I. Myoclonus and dystonia: a family study. Adv Neurol. 1988;50:385–9. [PubMed: 3400497]

  • Kurtis MM, San Luciano M, Yu Q, Goodman RR, Ford B, Raymond D, Pullman SL, Saunders-Pullman R. Clinical and neurophysiological improvement of SGCE myoclonus-dystonia with GPi deep brain stimulation. Clin Neurol Neurosurg. 2010;112:149–52. [PMC free article: PMC2815107] [PubMed: 19896264]

  • Kyllerman M, Forsgren L, Sanner G, Holmgren G, Wahlstrom J, Drugge U. Alcohol-responsive myoclonic dystonia in a large family: dominant inheritance and phenotypic variation. Mov Disord. 1990;5:270–9. [PubMed: 2259350]

  • Lang AE. Essential myoclonus and myoclonic dystonia. Mov Disord. 1997;12:127. [PubMed: 8990070]

  • Leung JC, Klein C, Friedman J, Vieregge P, Jacobs H, Doheny D, Kamm C, DeLeon D, Pramstaller PP, Penney JB, Eisengart M, Jankovic J, Gasser T, Bressman SB, Corey DP, Kramer P, Brin MF, Ozelius LJ, Breakefield XO. Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism. Neurogenetics. 2001;3:133–43. [PubMed: 11523564]

  • Leuzzi V, Carducci C, Carducci C, Cardona F, Artiola C, Antonozzi I. Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. Neurology. 2002;59:1241–3. [PubMed: 12391354]

  • Li JY, Cunic DI, Paradiso G, Gunraj C, Pal PK, Lang AE, Chen R. Electrophysiological features of myoclonus-dystonia. Mov Disord. 2008;23:2055–61. [PubMed: 18759341]

  • Liu X, Griffin IC, Parkin SG, Miall RC, Rowe JG, Gregory RP, Scott RB, Aziz TZ, Stein JF. Involvement of the medial pallidum in focal myoclonic dystonia: a clinical and neurophysiological case study. Mov Disord. 2002;17:346–53. [PubMed: 11921122]

  • Luciano MS, Ozelius L, Sims K, Raymond D, Liu L, Saunders-Pullman R. Responsiveness to levodopa in epsilon-sarcoglycan deletions. Mov Disord. 2009;24:425–8. [PubMed: 19133653]

  • Magariños-Ascone CM, Regidor I, Martinez-Castrillo JC, Gomez-Galan M, Figueiras-Mendez R. Pallidal stimulation relieves myoclonus-dystonia syndrome. J Neurol Neurosurg Psychiatry. 2005;76:989–91. [PMC free article: PMC1739713] [PubMed: 15965208]

  • Mahloudji M, Pikielny RT. Hereditary essential myoclonus. Brain. 1967;90:669–74. [PubMed: 6058147]

  • Maréchal L, Raux G, Dumanchin C, Lefebvre G, Deslandre E, Girard C, Campion D, Parain D, Frebourg T, Hannequin D. Severe myoclonus-dystonia syndrome associated with a novel epsilon-sarcoglycan gene truncating mutation. Am J Med Genet. 2003;119B:114–7. [PubMed: 12707948]

  • Marelli C, Canafoglia L, Zibordi F, Ciano C, Visani E, Zorzi G, Garavaglia B, Barzaghi C, Albanese A, Soliveri P, Leone M, Panzica F, Scaioli V, Pincherle A, Nardocci N, Franceschetti S. A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome. Mov Disord. 2008;23:2041–8. [PubMed: 18759336]

  • McNally EM, Ly CT, Kunkel LM. Human epsilon-sarcoglycan is highly related to alpha-sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene. FEBS Lett. 1998;422:27–32. [PubMed: 9475163]

  • 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 3rd, 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]

  • Misbahuddin A, Placzek M, Lennox G, Taanman JW, Warner TT. Myoclonus-dystonia syndrome with severe depression is caused by an exon-skipping mutation in the epsilon-sarcoglycan gene. Mov Disord. 2007;22:1173–5. [PubMed: 17230465]

  • Müller B, Hedrich K, Kock N, Dragasevic N, Svetel M, Garrels J, Landt O, Nitschke M, Pramstaller PP, Reik W, Schwinger E, Sperner J, Ozelius L, Kostic V, Klein C. Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia. Am J Hum Genet. 2002;71:1303–11. [PMC free article: PMC378568] [PubMed: 12444570]

  • Naito H, Oyanagi S. Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy. Neurology. 1982;32:798–807. [PubMed: 6808417]

  • Nardocci N, Zorzi G, Barzaghi C, Zibordi F, Ciano C, Ghezzi D, Garavaglia B. Myoclonus-dystonia syndrome: clinical presentation, disease course, and genetic features in 11 families. Mov Disord. 2008;23:28–34. [PubMed: 17853490]

  • Nishiyama A, Endo T, Takeda S, Imamura M. Identification and characterization of epsilon-sarcoglycans in the central nervous system. Brain Res Mol Brain Res. 2004;125:1–12. [PubMed: 15193417]

  • Nitschke MF, Erdmann C, Trillenberg P, Sprenger A, Kock N, Sperner J, Klein C. Functional MRI reveals activation of a subcortical network in a 5-year-old girl with genetically confirmed myoclonus-dystonia. Neuropediatrics. 2006;37:79–82. [PubMed: 16773505]

  • Nygaard TG, Raymond D, Chen C, Nishino I, Greene PE, Jennings D, Heiman GA, Klein C, Saunders-Pullman RJ, Kramer P, Ozelius LJ, Bressman SB. Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31. Ann Neurol. 1999;46:794–8. [PubMed: 10554001]

  • Obeso JA, Rothwell JC, Lang AE, Marsden CD. Myoclonic dystonia. Neurology. 1983;33:825–30. [PubMed: 6683367]

  • O'Riordan S, Ozelius LJ, de Carvalho Aguiar P, Hutchinson M, King M, Lynch T. Inherited myoclonus-dystonia and epilepsy: further evidence of an association? Mov Disord. 2004;19:1456–9. [PubMed: 15389977]

  • Papapetropoulos S, Argyriou AA, Polychronopoulos P, Spyridonidis T, Gourzis P, Chroni E. Frontotemporal and striatal SPECT abnormalities in myoclonus-dystonia: phenotypic and pathogenetic considerations. Neurodegener Dis. 2008;5:355–8. [PubMed: 18309231]

  • Park IS, Kim JS, An JY, Kim YI, Lee KS. Excellent response to oral zolpidem in a sporadic case of the myoclonus dystonia syndrome. Mov Disord. 2009;24:2172–3. [PubMed: 19735067]

  • Pennacchio LA, Lehesjoki AE, Stone NE, Willour VL, Virtaneva K, Miao J, D'Amato E, Ramirez L, Faham M, Koskiniemi M, Warrington JA, Norio R, de la Chapelle A, Cox DR, Myers RM. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1) Science. 1996;271:1731–4. [PubMed: 8596935]

  • Priori A, Bertolasi L, Pesenti A, Cappellari A, Barbieri S. Gamma-hydroxybutyric acid for alcohol-sensitive myoclonus with dystonia. Neurology. 2000;54:1706. [PubMed: 10762526]

  • Quinn NP. Essential myoclonus and myoclonic dystonia. Mov Disord. 1996;11:119–24. [PubMed: 8684380]

  • Quinn NP, Rothwell JC, Thompson PD, Marsden CD. Hereditary myoclonic dystonia, hereditary torsion dystonia and hereditary essential myoclonus: an area of confusion. Adv Neurol. 1988;50:391–401. [PubMed: 3400498]

  • Raymond D, Saunders-Pullman R, de Carvalho Aguiar P, Schule B, Kock N, Friedman J, Harris J, Ford B, Frucht S, Heiman GA, Jennings D, Doheny D, Brin MF, de Leon Brin D, Multhaupt-Buell T, Lang AE, Kurlan R, Klein C, Ozelius L, Bressman S. Phenotypic spectrum and sex effects in eleven myoclonus-dystonia families with epsilon-sarcoglycan mutations. Mov Disord. 2008;23:588–92. [PubMed: 18175340]

  • Ritz K, Gerrits MC, Foncke EM, van Ruissen F, van der Linden C, Vergouwen MD, Bloem BR, Vandenberghe W, Crols R, Speelman JD, Baas F, Tijssen MA. Myoclonus-dystonia: clinical and genetic evaluation of a large cohort. J Neurol Neurosurg Psychiatry. 2009;80:653–8. [PubMed: 19066193]

  • 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]

  • Saunders-Pullman R, Ozelius L, Bressman SB. Inherited myoclonus-dystonia. Adv Neurol. 2002a;89:185–91. [PubMed: 11968443]

  • Saunders-Pullman R, Shriberg J, Heiman G, Raymond D, Wendt K, Kramer P, Schilling K, Kurlan R, Klein C, Ozelius LJ, Risch NJ, Bressman SB. Myoclonus dystonia: possible association with obsessive-compulsive disorder and alcohol dependence. Neurology. 2002b;58:242–5. [PubMed: 11805251]

  • Scheidtmann K, Muller F, Hartmann E, Koenig E. Familial myoclonus-dystonia syndrome associated with panic attacks. Nervenarzt. 2000;71:839–42. [PubMed: 11082816]

  • Schüle B, Kock N, Svetel M, Dragasevic N, Hedrich K, De Carvalho Aguiar P, Liu L, Kabakci K, Garrels J, Meyer EM, Berisavac I, Schwinger E, Kramer PL, Ozelius LJ, Klein C, Kostic V. Genetic heterogeneity in ten families with myoclonus-dystonia. J Neurol Neurosurg Psychiatry. 2004;75:1181–5. [PMC free article: PMC1739169] [PubMed: 15258227]

  • Stark Z, Ryan MM, Bruno DL, Burgess T, Savarirayan R. Atypical Silver-Russell phenotype resulting from maternal uniparental disomy of chromosome 7. Am J Med Genet A. 2010;152A:2342–5. [PubMed: 20684011]

  • Suchowersky O, Davis JL, et al. 2000Thalamic surgery for essential myoclonus results in clinical but not functional improvement. Mov Disord 15S3P332.

  • Tai CH, Yen RF, Lin CH, Yen KY, Yip PK, Wu RM, Lee MJ. Focal brain glucose hypermetabolism in myoclonus-dystonia syndrome caused by an epsilon-sarcoglycan gene mutation. Parkinsonism Relat Disord. 2009;15:614–6. [PubMed: 19261534]

  • Tezenas du Montcel S, Clot F, Vidailhet M, Roze E, Damier P, Jedynak CP, Camuzat A, Lagueny A, Vercueil L, Doummar D, Guyant-Maréchal L, Houeto JL, Ponsot G, Thobois S, Cournelle MA, Durr A, Durif F, Echenne B, Hannequin D, Tranchant C, Brice A., French Dystonia Network. Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes. J Med Genet. 2006;43:394–400. [PMC free article: PMC2564513] [PubMed: 16227522]

  • Trottenberg T, Meissner W, Kabus C, Arnold G, Funk T, Einhaupl KM, Kupsch A. Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome. Mov Disord. 2001;16:769–71. [PubMed: 11481711]

  • Valente EM, Edwards MJ, Mir P, DiGiorgio A, Salvi S, Davis M, Russo N, Bozi M, Kim HT, Pennisi G, Quinn N, Dallapiccola B, Bhatia KP. The epsilon-sarcoglycan gene in myoclonic syndromes. Neurology. 2005;64:737–9. [PubMed: 15728306]

  • Valente EM, Misbahuddin A, Brancati F, Placzek MR, Garavaglia B, Salvi S, Nemeth A, Shaw-Smith C, Nardocci N, Bentivoglio AR, Berardelli A, Eleopra R, Dallapiccola B, Warner TT. Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity. Mov Disord. 2003;18:1047–51. [PubMed: 14502674]

  • Vidailhet M, Tassin J, Durif F, Nivelon-Chevallier A, Agid Y, Brice A, Durr A. A major locus for several phenotypes of myoclonus—dystonia on chromosome 7q. Neurology. 2001;56:1213–6. [PubMed: 11342690]

  • Xiao J, LeDoux MS. Cloning, developmental regulation and neural localization of rat epsilon-sarcoglycan. Brain Res Mol Brain Res. 2003;119:132–43. [PubMed: 14625080]

  • Yokoi F, Dang MT, Mitsui S, Li Y. Exclusive paternal expression and novel alternatively spliced variants of epsilon-sarcoglycan mRNA in mouse brain. FEBS Lett. 2005;579:4822–8. [PubMed: 16099459]

  • Zimprich A, Grabowski M, Asmus F, Naumann M, Berg D, Bertram M, Scheidtmann K, Kern P, Winkelmann J, Muller-Myhsok B, Riedel L, Bauer M, Muller 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]

Suggested Reading

  • Bressman SB. Genetics of dystonia: an overview. Parkinsonism Relat Disord. 2007;13 Suppl 3:S347–55. [PubMed: 18267263]

  • Esapa CT, Waite A, Locke M, Benson MA, Kraus M, McIlhinney RA, Sillitoe RV, Beesley PW, Blake DJ. SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Hum Mol Genet. 2007;16:327–42. [PubMed: 17200151]

  • Han F, Racacho L, Yang H, Read T, Suchowersky O, Lang AE, Grimes DA, Bulman DE. Large deletions account for an increasing number of mutations in SGCE. Mov Disord. 2008;23:456–60. [PubMed: 18098280]

  • Kinugawa K, Vidailhet M, Clot F, Apartis E, Grabli D, Roze E. Myoclonus-dystonia: an update. Mov Disord. 2009;24:479–89. [PubMed: 19117361]

  • Klein C, Gurvich N, Sena-Esteves M, Bressman S, Brin MF, Ebersole BJ, Fink S, Forsgren L, Friedman J, Grimes D, Holmgren G, Kyllerman M, Lang AE, de Leon D, Leung J, Prioleau C, Raymond D, Sanner G, Saunders-Pullman R, Vieregge P, Wahlstrom J, Breakefield XO, Kramer PL, Ozelius LJ, Sealfon SC. Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia. Ann Neurol. 2000;47:369–73. [PubMed: 10716258]

  • Klein C, Schilling K, Saunders-Pullman RJ, Garrels J, Breakefield XO, Brin MF, deLeon D, Doheny D, Fahn S, Fink JS, Forsgren L, Friedman J, Frucht S, Harris J, Holmgren G, Kis B, Kurlan R, Kyllerman M, Lang AE, Leung J, Raymond D, Robishaw JD, Sanner G, Schwinger E, Tabamo RE, Tagliati M. A major locus for myoclonus-dystonia maps to chromosome 7q in eight families. Am J Hum Genet. 2000;67:1314–9. [PMC free article: PMC1288573] [PubMed: 11022010]

  • Tycko B, Morison IM. Physiological functions of imprinted genes. J Cell Physiol. 2002;192:245–58. [PubMed: 12124770]

  • Weinstein LS. The role of tissue-specific imprinting as a source of phenotypic heterogeneity in human disease. Biol Psychiatry. 2001;50:927–31. [PubMed: 11750888]

  • Yokoi F, Dang MT, Li J, Li Y. Myoclonus, motor deficits, alterations in emotional responses and monoamine metabolism in epsilon-sarcoglycan deficient mice. J Biochem. 2006;140:141–6. [PubMed: 16815860]

Chapter Notes

Revision History

  • 26 January 2012 (me) Comprehensive update posted live
  • 19 December 2005 (me) Comprehensive update posted to live Web site
  • 11 June 2004 (ljo/cd) Revision: testing
  • 21 May 2003 (me) Review posted to live Web site
  • 5 May 2003 (ljo) Original submission