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GeneReviews provides information about selected national organizations and resources for the benefit of the reader. GeneReviews is not responsible for information provided by other organizations. Information that appears in the Resources section of a GeneReview is current as of initial posting or most recent update of the GeneReview. Search GeneTests for this disorder and select
for the most up-to-date Resources information.—ED.
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Information in the Molecular Genetics tables is current as of initial posting or most recent update. —ED.
Genetics clinics are a source of information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
Support groups have been established for individuals and families to provide information, support, and contact with other affected individuals. The Resources section may include disease-specific and/or umbrella support organizations.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
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. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Disease characteristics. Unverricht-Lundborg disease (EPM1) is a neurodegenerative disorder characterized by onset from age six to 15 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are mentally alert but show emotional lability, depression, and mild decline in intellectual performance over time.
Diagnosis/testing. EPM1 results from defective function of cystatin B, a cysteine protease inhibitor, as a consequence of mutations in the CSTB gene. The diagnosis can be confirmed by identifying disease-causing mutations in CSTB. Testing for the common dodecamer repeat expansion mutation and three other mutations is available on a clinical basis.
Management. Treatment of manifestations: Symptomatic pharmacologic and rehabilitative management, including psychosocial support, are the mainstay of care; valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures; clonazepam, approved by FDA for the treatment of myoclonic seizures, is an add-on therapy; high-dose piracetam is used to treat myoclonus; levetiracetam seems effective for both myoclonus and generalized seizures. Surveillance: lifelong clinical follow-up, including evaluation of the drug-treatment and rehabilitation. Agents/circumstances to avoid: Phenytoin aggravates the associated neurologic symptoms or even accelerates cerebellar degeneration; sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures.
Genetic counseling. EPM1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Prenatal testing is possible if both disease-causing mutations have been identified in an affected family member.
The diagnosis of Unverricht-Lundborg disease (EPM1) is suspected in a previously healthy child age six to 15 years who manifests the following:
Involuntary, action-activated myoclonic jerks and/or
Generalized tonic-clonic seizures
Photosensitive, generalized spike-and-wave and polyspike-and-wave paroxysms on EEG. The EEG is always abnormal, even before the onset of symptoms. The background activity is labile and usually slower than normal. Photosensitivity is marked [Koskiniemi, Toivakka et al 1974].
A gradual worsening of the neurologic symptoms (myoclonus and ataxia)
Normal magnetic resonance imaging of the brain
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Gene. CSTB is the only gene known to be associated with Unverricht-Lundborg disease [Pennacchio et al 1996].
CSTB. Virtually all affected individuals have an unstable expansion of a 12-nucleotide (dodecamer) repeat 5'-CCC-CGC-CCC-GCG-3' [Lalioti, Scott et al 1997] in at least one of the two altered CSTB alleles; the majority of individuals have two expanded repeats in abnormal allele range [Lafreniere et al 1997; Lalioti, Scott et al 1997; Virtaneva et al 1997].
The expanded dodecamer repeat mutation accounts for approximately 90% of Unverricht-Lundborg disease alleles found throughout the world.
About 99% of Finnish individuals have two expanded alleles.
Allele sizes
Normal alleles: 2-3 dodecamer repeats
Full penetrance alleles: ≥30 dodecamer repeats. The largest allele observed to date using Southern blotting is about 125 dodecamer repeats [Virtaneva et al 1997].
Alleles of questionable significance:
Alleles of 12-17 dodecamer repeats have been observed, but individuals with alleles in this range have not undergone thorough clinical evaluation for signs and symptoms of EPM1; therefore, one cannot say that the alleles are normal [Lalioti, Scott et al 1997].
Alleles of 4-11 dodecamer repeats and 18-29 dodecamer repeats have not been reported.
Clinical uses
Confirmatory diagnostic testing
Clinical testing
Sequence analysis is available on a clinical basis to detect CSTB mutations, including the five in Table 1 as well as novel variants.
Table 1 summarizes molecular genetic testing for this disorder.
| Test Method | Mutations Detected | Mutation Detection Frequency 1 | Test Availability |
|---|---|---|---|
| Targeted mutation analysis | Dodecamer repeat expansion in the promoter of CSTB | 99% of disease alleles in Finnish individuals; ~90% of disease alleles worldwide | Clinical
 |
| c.10G>C, c.67-1G>C, c.169-2A>G, c.202C>T, c.218_219delTC | Unknown | ||
| Sequence analysis | Mutations in CSTB | Unknown |
Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.
When heterozygosity for the dodecamer expansion is found in an affected individual, it is appropriate to pursue molecular genetic testing for other CSTB mutations in the second allele either by targeted mutation analysis or sequence analysis. If targeted mutation analysis for the five mutations does not identify the second mutation, sequence analysis may be appropriate.
No other phenotypes are known to be associated with mutations in CSTB.
In over half of individuals with Unverricht-Lundborg disease (EPM1), the first symptom is involuntary myoclonic jerks [Koskiniemi, Donner et al 1974; Norio & Koskiniemi 1979]. The myoclonic jerks are action activated and stimulus sensitive and may be provoked by light, physical exertion, and stress. They occur predominantly in the proximal muscles of the extremities and are asynchronous; they may be focal or multifocal and may generalize to a series of myoclonic seizures or even status myoclonicus (continuous myoclonic jerks involving a semi-loss of consciousness).
During the first five to ten years, the symptoms/myoclonic jerks characteristically progress and the individual may become severely incapacitated (wheelchair bound). Although the myoclonic jerks are disabling and resistant to therapy, the individual usually learns to tolerate them over time, provided that the psychosocial circumstances are good and depression is not too severe.
In almost half of individuals, the presenting symptom is tonic-clonic seizures [Koskiniemi, Donner et al 1974; Norio & Koskiniemi 1979]. There may also be absence, psychomotor, and/or focal motor seizures. Epileptic seizures, infrequent in the early stages of the disease, often increase in frequency during the ensuing three to seven years. Later they may cease entirely with appropriate antiepileptic drug treatment. In rare cases, tonic-clonic seizures do not occur.
Neurologic findings initially seem normal; however, experienced observers usually note recurrent, almost imperceptible myoclonus, especially in response to photic stimuli or other stimuli (threat, clapping of hands, nose tapping, reflexes) or to action (movements made during neurologic examination). Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are mentally alert but show emotional lability, depression, and mild decline in intellectual performance over time.
The disease course is inevitably progressive; however, the rate of deterioration especially in terms of walking capacity seems to vary even within the same family. Generalized tonic-clonic seizures are usually controlled with treatment, but myoclonic jerks may become severe, appear in series, and inhibit normal activities [Magaudda et al 2006]. The individual becomes depressed and progression ensues. Education is often interrupted because of emotional, social, and intellectual problems.
In the past, life span was shortened; many individuals died eight to 15 years after the onset of disease, usually before age 30 years. With better pharmacologic, physiotherapeutic, and psychosocial supportive treatment, life expectancy appearsf to be normal.
All individuals with mutations in CSTB develop similar disease manifestations. No correlation exists between the length of the expanded dodecamer repeat and the age of onset or disease severity [Lafreniere et al 1997; Lalioti, Scott et al 1997; Virtaneva et al 1997; Lalioti et al 1998]. Disease severity may vary among affected individuals within a family who have apparently similar repeat-size expansions.
Unverricht-Lundborg disease was previously called Baltic myoclonus or Baltic myoclonic epilepsy. These names should no longer be used because the condition occurs worldwide.
An identical disorder, found in individuals from the Mediterranean countries and called Mediterranean myoclonus, is now known to be EPM1 [Virtaneva et al 1997].
The term progressive myoclonus epilepsy (PME) covers a large group of various diseases characterized by myoclonus, epilepsy, and progressive neurologic deterioration.
EPM1 is the major cause of progressive myoclonus epilepsy in North America, but exact prevalence figures are not available.
EPM1 occurs worldwide, but its prevalence is increased in certain populations, e.g., in the Western Mediterranean (i.e., North African countries of Tunisia, Algeria, Morocco) where exact prevalence figures are not available and in Finland where its prevalence of 4:100,000 population is higher than anywhere else in the world. The incidence in Finland is about 1:20,000 births.
A founder effect in EPM1 on Reunion Island is evident, as all but one EPM1 chromosome in 14 individuals homozygous for the dodecamer repeat expansion had the same haplotype [Moulard et al 2003].
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
At the onset of Unverricht-Lundborg disease (EPM1), juvenile myoclonic epilepsy (JME), which has a favorable outcome, should be considered as a diagnostic alternative. Individuals with JME have a normal neurologic examination and the background of the EEG is undisturbed.
In case of progression, other forms of progressive myoclonus epilepsy, notably myoclonic epilepsy with ragged red fibers (MERRF), neuronal ceroid-lipofuscinoses, and Lafora disease, should be considered.
An inbred Arab family with an EPM1-like phenotype with somewhat earlier onset has been described [Berkovic et al 2005]. The phenotype in this family has been linked to chromosome 12, but the causative gene is unknown. In CSTB mutation-negative individuals with an EPM1-like phenotype of earlier onset, this disorder should be considered.
To establish the extent of disease in an individual diagnosed with Unverricht-Lundborg disease (EPM1):
A clinical evaluation including evaluation of walking, coordination, handwriting, school performance, and emotional features is essential.
Examination of myoclonus should include evaluation of myoclonus at rest, with action, and in response to stimuli.
EEG should be evaluated before therapy is initiated as it is most characteristic before use of anticonvulsive medication.
Symptomatic pharmacologic and rehabilitative management are the mainstay of patient care:
Valproic acid is the first drug of choice [Koskiniemi, Donner et al 1974; Norio & Koskiniemi 1979; Iivanainen & Himberg 1982; Somerville & Olanow 1982]. It diminishes myoclonus and the frequency of generalized seizures.
Clonazepam, the only drug approved by the Food and Drug Administration (FDA) for the treatment of myoclonic seizures, is used as add-on therapy [Iivanainen & Himberg 1982, Shahwan et al 2005].
High-dose piracetam has been formally studied and has been found useful in the treatment of myoclonus [Remy & Genton 1991, Koskiniemi et al 1998].
Levetiracetam has been evaluated in several series and seems to be effective for both myoclonus and generalized seizures.
Patients need lifelong clinical follow-up and psychosocial support including evaluation of the drug treatment and comprehensive rehabilitation.
Phenytoin should be avoided, since it has been found to have aggravating side effects on the associated neurologic symptoms or even deteriorating effects on the cerebellar degeneration [Eldridge et al 1983].
Sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin should in general be avoided as they may aggravate myoclonus and myoclonic seizures [Medina et al 2005].
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Brivaracetam, a SV2A ligand that differs from levetiracetam by its mechanism of action profile, has shown significant antiepileptic activity in experimental models of epilepsy and myoclonus. Brivaracetam has been granted orphan drug designation by the FDA (United States) for the treatment of symptomatic myoclonus, and by the EMEA (European Agency for the Evaluation of Medicinal Products; European Union) for the treatment of progressive myoclonic epilepsies.
Brivaracetam is currently being investigated as an add-on treatment for Unverricht-Lundborg disease in adolescents and adults.
Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.
Vagus nerve stimulator therapy reduces seizures and significantly improves cerebellar function on neurologic examination [Smith et al 2000].
N-acetylcysteine has been tried with variable results [Edwards et al 2002].
Genetics clinics are a source of information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
Support groups have been established for individuals and families to provide information, support, and contact with other affected individuals. The Resources section may include disease-specific and/or umbrella support organizations.
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. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Unverricht-Lundborg disease (EPM1) is inherited in an autosomal recessive manner.
Parents of a proband
The parents of an affected child are obligate heterozygotes and therefore carry one mutant allele.
Heterozygotes (carriers) are asymptomatic.
Sibs of a proband
At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
Heterozygotes (carriers) are asymptomatic.
Offspring of a proband
Several individuals with Unverricht-Lundborg disease, both males and females, have produced children.
The offspring of an individual with Unverricht-Lundborg disease are obligate heterozygotes (carriers) for a disease-causing mutation in the CSTB gene.
Because of the low carrier rate in the general population, the risk that an affected individual would have children with a carrier is extremely low except in genetic isolates.
Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.
Carrier testing is available to at-risk family members on a clinical basis once the mutations have been identified in the proband.
Carrier testing is available to the reproductive partners of a known carrier.
Family planning. The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
Testing of at-risk individuals during childhood. Because practically all affected individuals have their first symptoms before age 18 years, requests from parents for testing of asymptomatic at-risk individuals younger than age 18 years may arise. Consensus holds that asymptomatic individuals younger than age 18 years who are at risk for non-treatable disorders should not have testing. The principal arguments against testing asymptomatic individuals during childhood are that it removes their choice to know or not know this information, it raises the possibility of stigmatization within the family and in other social settings, and it could have serious educational and career implications [Bloch & Hayden 1990, Harper & Clarke 1990]. In addition, no preventive treatment is available.
Individuals younger than age 18 years who are symptomatic usually benefit from having a specific diagnosis established.
(See also the National Society of Genetic Counselors resolution on genetic testing of children and the American Society of Human Genetics and American College of Medical Genetics points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents.)
Testing of at-risk asymptomatic adults. Testing of at-risk asymptomatic adults for Unverricht-Lundborg disease is available using the same techniques described in Molecular Genetic Testing. Such testing is not useful in predicting whether symptoms will occur, or if they do, what the age of onset, severity, and type of symptoms, or rate of disease progression in asymptomatic individuals will be. When testing at-risk individuals for Unverricht-Lundborg disease, an affected family member should be tested first to confirm the molecular diagnosis in the family.
Testing for the disease-causing mutation in the absence of definite symptoms of the disease is predictive testing. At-risk asymptomatic adult family members may seek testing in order to make personal decisions regarding reproduction, financial matters, and career planning. Others may have different motivations including simply the "need to know." Testing of asymptomatic at-risk adult family members usually involves pre-test interviews in which the motives for requesting the test, the individual's knowledge of Unverricht-Lundborg disease, the possible impact of positive and negative test results, and neurologic status are assessed. Those seeking testing should be counseled about possible problems that they may encounter with regard to health, life, and disability insurance coverage, employment and educational discrimination, and changes in social and family interaction. Other issues to consider are implications for the at-risk status of other family members. Informed consent should be procured and records kept confidential. Individuals with a positive test result need arrangements for long-term follow-up and evaluations.
DNA banking. 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, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%. See DNA Banking for a list of laboratories offering this service.
Prenatal diagnosis for pregnancies at increased risk for the dodecamer repeat expansion or one of the five other mutations (see Table 1) is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.
Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.
Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutations have been identified. For laboratories offering PGD, see
Information in the Molecular Genetics tables is current as of initial posting or most recent update. —ED.
| Gene Symbol | Chromosomal Locus | Protein Name |
|---|---|---|
| CSTB | 21q22.3 | Cystatin-B |
Data are compiled from the following standard references: Gene symbol from HUGO; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from Swiss-Prot.
| Gene Symbol | Entrez Gene | HGMD |
|---|---|---|
| CSTB | 1476 (MIM No. 601145) | CSTB |
For a description of the genomic databases listed, click here.
Note: HGMD requires registration.
Normal allelic variants: CSTB consists of three exons, all of them coding, spanning roughly 2.5 kb of genomic DNA. Northern blot analysis shows a single transcript of approximately 0.8 kb [Pennacchio et al 1996]. One silent polymorphsism in CSTB (exon 1, g.431G>T; GenBank reference sequence U46692) has been reported [Lalioti, Mirotsou et al 1997].
Pathologic allelic variants: Ten different mutations have been identified [Pennacchio et al 1996; Lalioti, Mirotsou et al 1997; Lalioti, Scott et al 1997; Kagitani-Shimono et al 2002; de Haan et al 2004; Joensuu et al 2007].
All except one individual reported among more than 150 apparently unrelated families studied to date have had an unstable expansion of a 12-nucleotide (dodecamer; 5'-CCC-CGC-CCC-GCG-3') repeat unit [Lalioti, Scott et al 1997] on at least one disease allele, the majority of individuals having two disease-causing expansions [Lafreniere et al 1997; Lalioti, Scott et al 1997; Virtaneva et al 1997]. The expanded repeat is located 175 bp upstream from the translation initiation codon in the promoter region of the CSTB gene. This mutation accounts for approximately 90% of Unverricht-Lundborg disease alleles found throughout the world, and 99% of affected Finnish individuals have two disease-causing dodecamer expansions.
Nine mutations occur in the transcription unit of CSTB and affect one or two nucleotides (GenBank reference sequence NM_000100). Three of these are missense mutations (c.10G>C, c.149G>A, c.212A>C), four affect splicing (c.67-1G>C, c.168G>A, c.168+1_18del, c.169-2A>G), and two predict truncated protein products (c.202C>T, c218_219delTC). The c.67-1G>C, c.202C>T, and c.218_219delTC mutations have been observed in more than one affected individual [Pennacchio et al 1996; Bespalova, Adkins et al 1997; Bespalova, Pranzatelli et al 1997; Lafreniere et al 1997; Lalioti, Mirotsou et al 1997], whereas the remaining six have been identified in one individual each [Lalioti, Mirotsou et al 1997; Kagitani-Shimono et al 2002; de Haan et al 2004; Joensuu et al 2007]. The c.10G>C mutation is the only mutation reported that does not occur in compound heterozygous form with the dodecamer repeat expansion mutation [Lalioti, Mirotsou et al 1997].
Normal gene product: Cystatin B is an inhibitor of several papain-family cysteine proteases, cathepsins, which are lysosomal enzymes [Turk & Bode 1991]. CSTB is a ubiquitously expressed 98-amino acid protein and has a molecular weight of 11 kd. Its physiologic function is unknown. Within cells, CSTB shows lysosomal, nuclear, and/or cytosolic localization [Alakurtti et al 2005].
Cstb-deficient knockout mice display a phenotype similar to the human disease with progressive ataxia and myoclonic seizures [Pennacchio et al 1998]. The mice show neuronal apoptosis (especially of cerebellar granule cells), atrophy, and gliosis as well as increased expression of apoptosis and glial activation genes [Pennacchio et al 1998, Lieuallen et al 2001, Shannon et al 2002]. In mice double-deficient for CSTB and one of its target proteases, cathepsin B, significantly reduced cerebellar granule cell apoptosis establishes cathepsin B as a contributor to the disease pathogenesis [Houseweart et al 2003].
Abnormal gene product: The major mutation underlying Unverricht-Lundborg disease results in a significantly reduced amount of CSTB mRNA — 5%-10% expression of that found in controls [Joensuu et al 2007]. Consequently, cells of individuals with Unverricht-Lundborg disease display significantly reduced CSTB protein expression [Alakurtti et al 2005, Joensuu et al 2007] and reduced CSTB inhibitory activity [Rinne et al 2002]. Cathepsin activity is significantly increased [Rinne et al 2002].
The c.67-1G>C, c.168G>A, c.168+1_18del, and c.169-2A>G mutations affect splice sites and predict splicing defects. The c.67-1G>C mutation results in skipping of exon 2 predicting an in-frame deletion of 34 amino acids [Bespalova, Pranzatelli et al 1997]. The c.67-1G>C mutant mRNAs seem to be unstable [Joensuu et al 2007]. The c.168+1_18del mutation also results in aberrant splicing of CSTB with two different transcripts, but the consequences of the c.168G>A and c.169-2A>G splice site mutations have not been experimentally tested. Mutations c.202C>T and c.218_219delTC predict truncated proteins of 68 and 74 amino acids (including two code-shifted amino acids), respectively. The c.202C>T (p.Arg68X) mutant transcript and protein are unstable [Alakurtti et al 2005, Joensuu et al 2007], implying reduced CSTB expression as the primary pathophysiologic mechanism. The c.10G>C mutation results in the substitution of a highly conserved glycine to an arginine at amino acid position 4 (G4R), critical for cathepsin binding [Lalioti, Mirotsou et al 1997]. The c.149G>A mutation results in the substitution of glycine to glutamic acid (p.Gly50Glu) [Joensuu et al 2007]. It affects the highly conserved QVVAG-motif in the first beta-hairpin loop important for the complex formation with cathepsins. The c.212A>C mutation results in the substitution of a glutamine at position 71 by a proline (p.Gln71Pro) [de Haan et al 2004]. The glutamine does not interact directly with target proteases, but is located proximal to the second hairpin loop, which also contributes to protease binding. All three missense mutant proteins fail to associate with lysosomes implying the physiologic importance of CSTB-lysosome association [Alakurtti et al 2005, Joensuu et al 2007].
GeneReviews provides information about selected national organizations and resources for the benefit of the reader. GeneReviews is not responsible for information provided by other organizations. Information that appears in the Resources section of a GeneReview is current as of initial posting or most recent update of the GeneReview. Search GeneTests for this disorder and select
for the most up-to-date Resources information.—ED.
American Epilepsy Society
342 North Main Street
West Hartford CT 06117-2507
Phone: 860-586-7505
Fax: 860-586-7550
Email: info@aesnet.org
www.aesnet.org
Epilepsy Foundation
8301 Professional Place
East Landover, MD 20785-2238
Phone: 800-EFA-1000 (800-332-1000); 301-459-3700
Fax: 301-577-4941
Email: webmaster@efa.org
www.efa.org
WE MOVE (Worldwide Education and Awareness for Movement Disorders)
204 West 84th Street
New York NY 10024
Phone: 800-437-MOV2 (800-437-6683)
Fax: 212-875-8389
Email: wemove@wemove.org
www.wemove.org
Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page.
No specific guidelines regarding genetic testing for this disorder have been developed.
Reeta Kälviäinen, PhD (2007-present)
Marja-Leena Koskiniemi, MD, PhD; University of Helsinki (2004-2007)
Anna-Elina Lehesjoki, MD, PhD (2004-present)
18 September 2007 (cd) Revision: sequence analysis available on a clinical basis
12 February 2007 (me) Comprehensive update posted to live Web site
24 June 2004 (me) Review posted to live Web site
6 February 2004 (ael) Original submission
