7/30/2019 Emery Dreifuse
1/32
Bookshelf ID: NBK1436PMID: 20301609
Emery-Dreifuss Muscular Dystrophy
Gisle Bonne, PhD, France Leturcq, MD, and Rabah Ben Yaou, MD.
Author Information
Initial Posting: September 29, 2004; Last Revision: August 24, 2010.
Go to:
Summary
Disease characteristics. Emery-Dreifuss muscular dystrophy (EDMD) is characterized bythe clinical triad of joint contractures that begin in early childhood, slowly progressive
muscle weakness and wasting initially in a humero-peroneal distribution that later extends to
the scapular and pelvic girdle muscles, and cardiac involvement that may manifest as
palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure.
Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both
inter- and intrafamilial variability. Clinical variability ranges from early onset with severe
presentation in childhood to late onset with slow progression in adulthood. In general, joint
contractures appear during the first two decades, followed by muscle weakness and wasting.
Cardiac involvement usually occurs after the second decade.
Diagnosis/testing. The three genes known to be associated with EDMD areEMD (encodingemerin) andFHL1 (encoding FHL1), which cause X-linked EDMD (XL-EDMD); andLMNA
(encoding lamin A and C), which causes autosomal dominant EDMD (AD-EDMD) and
autosomal recessiveEDMD (AR-EDMD). For all forms of EDMD the diagnosis is based on
clinical findings and family history. The diagnosis of X-linked EDMD also relies on failure
to detect emerin or FHL1 protein in various tissues and molecular genetic testing ofEMD or
FHL1. The diagnosis of AD-EDMD and AR-EDMD also relies on molecular genetic testing
ofLMNA.
Management.Treatment of manifestations: surgery to release contractures and manage
scoliosis as needed; aids (canes, walkers, orthoses, wheelchairs) as needed to help
ambulation; treatment for cardiac arrhythmias, AV conduction disorders, congestive heart
failure, including antiarrhythmic drugs, cardiac pacemaker, implantable cardioverter
defibrillator (ICD); heart transplantation for the end stages of heart failure as appropriate;
respiratory aids (respiratory muscle training, assisted coughing techniques, mechanical
ventilation) as needed.
Prevention of primary manifestations: physical therapy and stretching to prevent
contractures; implantation of cardiac defibrillators to reduce risk of sudden death.
Prevention of secondary complications: antithromboembolic drugs to prevent cerebral
thromboembolism of cardiac origin in those with decreased left ventricular function or atrialarrhythmias.
http://www.ncbi.nlm.nih.gov/pubmed/20301609http://www.ncbi.nlm.nih.gov/books/NBK1436/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/intrafamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/NBK1436/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/intrafamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/pubmed/203016097/30/2019 Emery Dreifuse
2/32
Surveillance: annual cardiac assessment (ECG, Holter monitoring, echocardiography);
monitoring of respiratory function.
Agents/circumstances to avoid: triggering agents for malignant hyperthermia, such as
depolarizing muscle relaxants (succinylcholine) and volatile anesthetic drugs (halothane,
isoflurane); obesity.
Testing of relatives at risk: cardiac evaluation for relatives at risk for AD-EDMD and female
carriers of XL-EDMD.
Genetic counseling. EDMD is inherited in an X-linked, autosomal dominant, orautosomal
recessive manner. XL-EDMD: If the mother of aproband has a disease-causing mutation, the
chance of transmitting it in each pregnancy is 50%. Males who inherit the mutation will be
affected; females who inherit the mutation will be carriers. Female carriers are usually
asymptomatic, but they are at risk of developing a cardiac disease, progressive muscular
dystrophy, and/or an EDMDphenotype.AD-EDMD: 76% of probands with AD-EDMD
have a de novo LMNA mutation. Each child of an individual with AD-EDMD has a 50%chance of inheriting the mutation. AR-EDMD: 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 neither affected nor a carrier. Prenatal testing for
pregnancies at increased risk is possible if the disease-causing mutation has been identified in
a family member.
Go to:
Diagnosis
Clinical Diagnosis
The clinical diagnosis of Emery-Dreifuss muscular dystrophy (EDMD) is based on the
presence of the following triad [Emery 2000]:
Early contractures of the elbow flexors, Achilles tendons (heels), and neck extensors
resulting in limitation of neck flexion, followed by limitation of extension of the
entire spine
Slowly progressive wasting and weakness typically of the humero-
peroneal/scapulo-peroneal muscles in the early stages
Cardiac disease with conduction defects and arrhythmias
o Atrial fibrillation, flutter and standstill, supraventricular and ventricular
arrhythmias, and atrio-ventricular and bundle-branch blocks may be identified
on resting electrocardiography (ECG) or by 24-hour ambulatory ECG.
o Dilated or hypertrophic cardiomyopathy may be detected by the performance
of echocardiographic evaluation.
Other clinical findings are nonspecific:
Electromyogram (EMG) usually shows myopathic features with normal nerve
conduction studies, but neuropathic patterns have been described for X-linked EDMD
http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/proband/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/proband/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.emery.2000.228http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/proband/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.emery.2000.2287/30/2019 Emery Dreifuse
3/32
(XL-EDMD) [Hopkins et al 1981] and forautosomal dominantEDMD (AD-EDMD)
[Witt et al 1988].
CT scan of muscle shows a diffuse pattern of involvement affecting the biceps,
soleus, peroneal, external vasti, gluteus, and paravertebral muscles [Graux et al 1993].
Characteristic findings in the calf muscles on MRI have been reported in AD-EDMD
[Mercuri et al 2002].
Testing
Other nonspecific laboratory findings:
Serum CK concentration is normal or moderately elevated (2-20 times upper normal
level). Increases in serum CK concentration are more often seen at the beginning of
the disease than in later stages [Bonne et al 2000,Bonne et al 2002].
Muscle histopathology shows nonspecific myopathic or dystrophic changes,
including variation in fiber size, increase in internal nuclei, increase in endomysial
connective tissue, and necrotic fibers. Electron microscopy may reveal specific
alterations in nuclear architecture [Fidzianska et al 1998,Sabatelli et al 2001, Sewry
et al 2001,Fidzianska & Hausmanowa-Petrusewicz 2003, Fidzianska & Glinka 2007].
Muscle biopsy is now rarely performed for diagnostic purposes because of the lack of
specificity of the dystrophic changes observed.
Immunodetection of emerin. In normal individuals, the protein emerin is
ubiquitously expressed on the nuclear membrane. Emerin can be detected by
immunofluorescence and/or by western blotin various tissues: exfoliative buccal
cells, lymphocytes, lymphoblastoid cell lines, skin biopsy, or muscle biopsy [Manilal
et al 1997,Mora et al 1997] (see GeneTests Laboratory Directory).
o
In individuals with XL-EDMD, emerin is absent in 95% [Yates & Wehnert1999].
o In female carriers of XL-EDMD, emerin is absent in varying proportions in
nuclei, as demonstrated by immunofluorescence. However,western blot is not
reliable in carrierdetection because it may show either a normal amount or
reduced amount of emerin, depending on the proportion of nuclei expressing
emerin.
o In individuals with AD-EDMD, emerin is normally expressed.
Immunodetection of FHL1. In controls, the three FHL1 isoforms (A, B, and C) are
ubiquitously expressed in the cytoplasm as well as in the nucleus. The isoforms can
be detected by immunofluorescence and/orwestern blot in fresh muscle biopsy or
myoblasts, fibroblasts, and cardiomyocytes [Sheikh et al 2008,Gueneau et al 2009].o In individuals withFHL1-related XL-EDMD, FHL1 is absent or significantly
decreased [Gueneau et al 2009].
o In female carriers ofFHL1-related XL-EDMD, FHL1 is expected to be
variably expressed.
Immunodetection of lamins A/C. Lamins A/C are expressed at the nuclear rim (i.e.,
nuclear membrane) and within the nucleoplasm (i.e., nuclear matrix). Depending on
the antibody used, lamins A/C can be localized to both the nuclear membrane and
matrix or to the nuclear matrix only. However, this test is not reliable for confirmation
of the diagnosis of AD-EDMD because in AD-EDMD lamins A/C are always present
because of the expression of the wild typeallele at the nuclear membrane and in the
nuclear matrix.
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hopkins.1981.230http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.witt.1988.230http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.graux.1993.554http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2002.10http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2002.187http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2002.187http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.1998.88http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sabatelli.2001.826http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sabatelli.2001.826http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sewry.2001.281http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sewry.2001.281http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sewry.2001.281http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.2003.47http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.2007.47http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/specificity/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1997.63http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1997.63http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1997.63http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mora.1997.249http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.199http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.199http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isoforms/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sheikh.2008.3870http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sheikh.2008.3870http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/allele/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/allele/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hopkins.1981.230http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.witt.1988.230http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.graux.1993.554http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2002.10http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2002.187http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.1998.88http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sabatelli.2001.826http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sewry.2001.281http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sewry.2001.281http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.2003.47http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fidzianska.2007.47http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/specificity/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1997.63http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1997.63http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mora.1997.249http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.199http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.199http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isoforms/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/western-blot/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sheikh.2008.3870http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/allele/7/30/2019 Emery Dreifuse
4/32
Molecular Genetic Testing
Genes. The three genes known to be associated with EDMD encode ubiquitous proteins
localized either in the nuclear membrane or in the cytoplasm and nucleoplasm.
EMD, a cause of XL-EDMD, encodes emerin [Bione et al 1994]. FHL1, a cause of XL-EDMD, encodes FHL1 [Gueneau et al 2009].
LMNA, a cause of AD-EDMD and AR-EDMD, encodes lamins A and C [Bonne et al
1999].
Other loci. About 64% of individuals with a diagnosis of EDMD who have emerin detected
on immunocytochemistry and/or immunoblotting have nomutationidentified inEMD,
FHL1, orLMNA, suggesting that these individuals are either misdiagnosed or that other as-
yet unidentified genes are involved in EDMD [Gueneau et al 2009].
Clinical testing
EMD
Sequence analysis/mutation scanning. Sequencing ofEMD (6 exons, 5 short
introns, andpromoter region) detects anEMD mutation in more than 99% of
individuals with established X-linked inheritance and/or with no emerin detected by
immunodetection methods [Manilal et al 1998]. Note: Sequence analysis of genomic
DNA cannot detect deletionof an exon(s) or whole-gene deletions on the X
chromosome in carrierfemales.
Deletion/duplication analysis detects exonic, multiexonic, or whole-gene deletions
ofEMD.
LMNA
Sequence analysis of the coding regions ofLMNA (12 exons and their flanking
intronic regions) detects mutations in 100% of individuals withLMNA sequence
variants (missense and nonsense mutations, small deletions/insertions); however, this
represents only about 45% of individuals with AD-EDMD because (1) large deletions
and duplications involving one or several exons are not detected and (2) other not-yet
discovered genes could be implicated in AD-EDMD [Bonne et al 2000,Brown et al
2001, Bonne et al 2003, Vytopil et al 2003].
Complementary DNA(cDNA) sequencing may be helpful to confirm the transcript
variants resulting from splice-site mutations.
Deletion/duplication analysis detects exonic, multiexonic or whole-gene deletions of
LMNA. Three large deletions have been identified to date. One of them encompasses
thepromoter regionand the beginning ofexon 1 and is responsible for a neurogenic
variant of EDMD [Walter et al 2005]. The two others, deleting exon 1 [van Tintelen
et al 2007] and exons 3 to 12 [Gupta et al 2010] respectively, are responsible for
isolatedcardiac disease.
FHL1
Sequence analysis of the eight exons, seven introns, andpromoter region detects a
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bione.1994.323http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.1999.285http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.1999.285http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1998.855http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2003.e132http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.walter.2005.40http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vantintelen.2007.2430http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vantintelen.2007.2430http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gupta.2010.365http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bione.1994.323http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.1999.285http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.1999.285http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1998.855http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2003.e132http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.walter.2005.40http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vantintelen.2007.2430http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vantintelen.2007.2430http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gupta.2010.365http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/promoter-region/7/30/2019 Emery Dreifuse
5/32
mutation in more than 99% of individuals with established X-linked inheritance and
with reduced or absent FHL1 by immunodetection methods [Gueneau et al 2009].
Table 1. Summary of Molecular Genetic Testing Used in Emery-Dreifuss Muscular
Dystrophy
Gene
Symbol
% of EDMD
Attributed to
Mutations in
This Gene
Test MethodMutations
Detected
Mutation
Detection
Frequency 1
Test
Availability
EMD~61% of X-
linked EDMD 2
Sequence analysis or
mutation scanning3Sequence
variants 4, 5
99% 6, 7 8Clinical
Deletion/duplication
analysis 9, 10
Deletion of
exon(s) or
entiregene
FHL1 ~10% of X-linked EDMD 2 Sequence analysis ormutation scanning3 Sequencevariants 4, 5 99%6, 7, 8, 11 Clinical
LMNA
~45% AD-
EDMD;
Unknown for
AR-EDMD 12
Sequence analysis or
mutation scanning3Sequence
variants 4, 599%
Clinical
Deletion/duplication
analysis 9, 10
Deletion of
exon(s) or
entiregene13Unknown
Test Availability refers to availability in the GeneTests Laboratory Directory.
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.
1. The ability of the test method used to detect a mutation that is present in the
indicated gene
2. Estimates are based on the published experience in France [Gueneau et al 2009].
SinceFHL1 was only recently reported as causative of XL-EDMD, a better
understanding of its prevalence will emerge with time and expanded use of testing.
3. Sequence analysis and mutation scanningof the entire gene can have similar
detection frequencies; however, detection rates for mutation scanning may vary
considerably among laboratories based on specific protocols used.
4. Examples of mutations detected bysequence analysismay include small intragenic
deletions/insertions and missense, nonsense, and splice site mutations.
5. Small intragenic deletions/insertions, missense, nonsense, and splice site mutations.
6. Males with an established X-linked inheritance or individuals with no emerinexpression as determined by immunodetection studies of muscle tissue
http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/221498?db=genetestshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319279?db=genetestshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2378?db=genetestshttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/duplication/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation-scanning/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/7/30/2019 Emery Dreifuse
6/32
7. Lack of amplification by PCRprior to sequence analysis can suggest a putative
exonic or whole-genedeletion on the X chromosome in affected males; confirmation
may require additional testing bydeletion/duplication analysis.
8. Sequence analysis of genomic DNA cannot detectdeletionof anexon(s) or whole-
gene deletions on the X chromosomein carrierfemales.
9. Testing that identifies deletions/duplications not readily detectable by sequence
analysis of genomic DNA; a variety of methods including quantitative PCR, long-
range PCR, multiplex ligation-dependentprobe amplification (MLPA), or targeted
array GH (gene/segment-specific) may be used. A full array GH analysis that detects
deletions/duplications across the genome may also include this gene/segment. See
array GH.
10. Extent ofdeletion detected may vary by method and by laboratory.
11. Males with an established X-linked inheritance or individuals with no or highlyreduced FHL1 expression as determined by immunodetection studies of muscle tissue
12. AR-EDMD is very rare. To date only oneLMNAmutation in a homozygous state
leading to AR-EDMD has been reported [Raffaele Di Barletta et al 2000].
13. Only three large deletions have been identified to date.
Interpretation of test results. For issues to consider in interpretation ofsequence analysis
results, clickhere.
Testing Strategy
To confirm/establish the diagnosis in a proband
If the family historyclarifies themode of inheritance, testing ofEMD andFHL1
should be performed for XL-EDMD andLMNA for AD-EDMD or AR-EDMD.
In the absence of an informative family history:
o Foraffected males: Emerin and FHL1 immunodetection studies help to
distinguish between XL- and AD-EDMD and thus determine the appropriate
gene formolecular genetic testing.
o Foraffected females who are simplex cases (i.e., a single occurrence in afamily): Carrier females rarely manifest X-linked EDMD; thus, affected
females are much more likely to have AD-EDMD andLMNA should be
analyzed before considering analysis of the X-linked genes.
Ifsequence analysis does not identify aEMDmutationin those with possible XL-
EDMD, deletion/duplication analysis should be considered.
Ifsequence analysis does not identify aLMNAmutationin those with suspected AD-
EDMD or AR-EDMD, deletion/duplication analysis may be appropriate even though
whole-exon or multi-exon deletions ofLMNA are rare.
Carrier testing
http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/polymerase-chain-reaction-pcr/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/quantitative-pcr/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/quantitative-pcr/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/probe/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genome/http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_lab_service_id/234754?db=genetestshttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/app2/http://www.ncbi.nlm.nih.gov/books/n/gene/app2/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/proband/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mode-of-inheritance/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mode-of-inheritance/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/polymerase-chain-reaction-pcr/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/carrier/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dna/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/quantitative-pcr/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/probe/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genome/http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_lab_service_id/234754?db=genetestshttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/app2/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/proband/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mode-of-inheritance/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/family-history/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/deletion-duplication-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/exon/7/30/2019 Emery Dreifuse
7/32
X-linked EDMD. Carrier testing for at-risk relatives requires prior identification of
theEMD orFHL1disease-causing mutationin the family.
Note: (1) Carriers are heterozygotes for this X-linked disorder and may develop
clinical findings related to the disorder. (2) Identification of female carriers requires
either (a) prior identification of the disease-causing mutation in the family or, (b) if anaffected male is not available for testing,molecular genetic testingfirst bysequence
analysis, and then, if no mutation is identified, by methods to detect gross structural
abnormalities.
Autosomalrecessive EDMD. Carrier testing for at-risk relatives requires prior
identification of the disease-causingLMNA mutations in the family.
Note: Carriers are heterozygotes for this autosomal recessivedisorder and are not at
risk of developing the disorder.
Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies
require prior identification of the disease-causing mutation in families with X-linked EDMDandautosomal dominant EDMD, and of the disease-causing mutations in families with
autosomal recessiveEDMD.
Note: It is the policy ofGeneReviews to include information on preimplantation genetic
diagnosis available from laboratories listed in the GeneTests Laboratory Directory; inclusion
does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or
reviewer(s).
Genetically Related (Allelic) Disorders
EMD
The disorders caused by mutations inEMD are called emerinopathies and affect striated
muscles:
X-linked LGMD (limb-girdle muscular dystrophy)phenotype caused bymutationin
EMD; rarely reported [Ura et al 2007,Fanin et al 2009]
X-linked isolated cardiac disease with prominent sinus node disease and atrial
fibrillation [Ben Yaou et al 2007, Karst et al 2008]
FHL1
FHL1-related diseases include three allelic disorders characterized by the presence of
reducing bodies detected on histopathology:
Reducing body myopathy [Schessl et al 2008]
X-linked scapuloperoneal myopathy [Quinzii et al 2008]
Some cases of rigid spine syndrome [Shalaby et al 2008]
Other allelicFHL1-related diseases:
X-linked myopathy with postural muscle atrophy (X-MPMA) and generalized musclehypertrophy or X-MPMA in which reducing bodies are absent and FHL1 protein is
http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ura.2007.1038http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fanin.2009.1432http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fanin.2009.1432http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2007.1883http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.karst.2008.510http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.schessl.2008.904http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quinzii.2008.208http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.shalaby.2008.959http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/affected/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/molecular-genetic-testing/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/sequence-analysis/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/disease-causing-mutation/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ura.2007.1038http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fanin.2009.1432http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2007.1883http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.karst.2008.510http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.schessl.2008.904http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quinzii.2008.208http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.shalaby.2008.9597/30/2019 Emery Dreifuse
8/32
reduced on immunodetection (making this disorder similar toFHL1-related EDMD)
[Windpassinger et al 2008]
X-linked hypertrophic cardiomyopathy [Gueneau et al 2009]
LMNA
The disorders caused by mutations inLMNA are called "laminopathies:"
Disorders of striated muscle *
LGMD1B, an autosomal dominantform oflimb-girdle muscular dystrophy associated
with atrioventricular conduction defect [van der Kooi et al 1996, Muchir et al 2000]
CMD1A or DCM-CD, anautosomal dominant form of dilated cardiomyopathy with
cardiac conduction defects [Fatkin et al 1999, Bcane et al 2000]
Autosomal dominant dilated cardiomyopathy (DCM) with apical left ventricular
aneurysm without atrio-ventricular block [Forissier et al 2003] or early atrial
fibrillation [Sebillon et al 2003] or left ventricular non-compaction [Hermida-Prieto etal 2004]
Autosomal dominant quadriceps myopathy associated with dilated cardiomyopathy
and cardiac conduction defects [Charniot et al 2003]
Neurogenic variant of EDMD [Walter et al 2005]
LMNA-related congenital muscular dystrophy (L-CMD) [Quijano-Roy et al 2008]
* Note: (1) These may not truly be allelic disorders because the phenotypeoverlaps with
EDMD. See comments in Genotype-Phenotype Correlations. (2) Laminopathies affecting
striated muscles are important to recognize because of the severity of the dilated
cardiomyopathy associated with conduction/rhythm (DCM-CD) disorders, and the high
frequency of sudden death [van Berlo et al 2005]. (3) See also Dilated Cardiomyopathy
Overview.
Disorders of peripheral nerve
CMT2B1, an autosomal recessive form of axonal Charcot-Marie-Tooth disease with
the foundermutation p.Arg298Cys [De Sandre-Giovannoli et al 2002] (see Charcot-
Marie-Tooth type 2)
Autosomal dominant CMT2 associated with muscular dystrophy, cardiomyopathy and
leukonychia [Goizet et al 2004].
Autosomal dominant CMT2 associated with myopathy [Benedetti et al 2005].
Disorders of fatty tissues. Autosomal dominantDunnigan type familial partial lipodystrophy
(FPLD) [Shackleton et al 2000]. The majority of FPLD cases are caused byLMNA mutations
affecting arginine codon482, leading to several amino acid substitutions [Bonne et al 2003].
Isolated metabolic manifestations without lipodystrophy have been also reported [Young et al
2005, Decaudain et al 2007]
Disorders involving several tissues
Autosomal dominant muscular dystrophy, dilated cardiomyopathy, and partial
lipodystrophy [Garg et al 2002, van der Kooi et al 2002]
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.windpassinger.2008.88http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanderkooi.1996.636http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muchir.2000.1453http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fatkin.1999.1715http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-lmna/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.forissier.2003.821http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sebillon.2003.560http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hermidaprieto.2004.50http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hermidaprieto.2004.50http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.charniot.2003.473http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.walter.2005.40http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/congenital/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quijanoroy.2008.177http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.GenotypePhenotype_Correlationshttp://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanberlo.2005.79http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-ov/http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-ov/http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-ov/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2002.726http://www.ncbi.nlm.nih.gov/books/n/gene/cmt2/http://www.ncbi.nlm.nih.gov/books/n/gene/cmt2/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goizet.2004.E29http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benedetti.2005.1019http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/familial/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.shackleton.2000.153http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/codon/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/codon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.young.2005.1873http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.young.2005.1873http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.decaudain.2007.4835http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.garg.2002.549http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanderkooi.2002.620http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.windpassinger.2008.88http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanderkooi.1996.636http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muchir.2000.1453http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.fatkin.1999.1715http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-lmna/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.forissier.2003.821http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sebillon.2003.560http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hermidaprieto.2004.50http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hermidaprieto.2004.50http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.charniot.2003.473http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.walter.2005.40http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/congenital/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quijanoroy.2008.177http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.GenotypePhenotype_Correlationshttp://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanberlo.2005.79http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-ov/http://www.ncbi.nlm.nih.gov/books/n/gene/dcm-ov/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2002.726http://www.ncbi.nlm.nih.gov/books/n/gene/cmt2/http://www.ncbi.nlm.nih.gov/books/n/gene/cmt2/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goizet.2004.E29http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benedetti.2005.1019http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/familial/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.shackleton.2000.153http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/codon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.young.2005.1873http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.young.2005.1873http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.decaudain.2007.4835http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.garg.2002.549http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanderkooi.2002.6207/30/2019 Emery Dreifuse
9/32
Mandibuloacral dysplasia (MAD) (autosomal recessive). Founder mutations are
reported in MAD (p.Arg527His) [De Sandre-Giovannoli et al 2002,Novelli et al
2002].
Generalized lipoatrophy, insulin-resistant diabetes mellitus, disseminated
leukomelanodermic papules, liver steatosis, and cardiomyopathy (LDHCP) [Caux et
al 2003] Hutchinson-Gilford progeria syndrome (HGPS) (autosomal dominant). Mutations in
codon 608 are associated with HGPS [De Sandre-Giovannoli et al 2003, Eriksson et al
2003].
Atypical Werner syndrome (autosomal dominant) [Chen et al 2003]
Restrictive dermopathies such as a lethal neonatal laminopathy [Navarro et al 2004]
Progeria, arthropathy, and calcinosis of tendons [Van Esch et al 2006]
Heart-hand syndrome, Slovenian type [Renou et al 2008]
Silent normal allelic variants ofLMNA. Some silent normal sequence variants ofLMNA are
also reported to be related to susceptibility to obesity and to insulin resistance [Hegele et al
2001a,Hegele et al 2001b, Murase et al 2002].
Go to:
Clinical Description
Natural History
AD-EDMD and XL-EDMD have similar, but not identical, neuromuscular and cardiac
involvement [Wulff et al 1997, Manilal et al 1998,Yates et al 1999,Bcane et al 2000,
Bonne et al 2000, Felice et al 2000,Raffaele Di Barletta et al 2000,Brown et al 2001,Borianiet al 2003,Vytopil et al 2003,Gueneau et al 2009,Knoblauch et al 2010].
EDMD is characterized by the presence of the following clinical triad:
Joint contractures that begin in early childhood in both XL-EDMD and AD-EDMD.
In XL-EDMD, joint contractures are usually the first sign, whereas in AD-EDMD,
joint contractures may appear after the onset of muscle weakness. Joint contractures
predominate in the elbows, ankles, and postcervical muscles (responsible for
limitation of neck flexion followed by limitation in movement of the entire spine).
The degree and the progression of contractures are variable and not always age related
[Bonne et al 2000]. Severe contractures may lead to loss of ambulation by limitation
of movement of the spine and lower limbs.
Slowly progressive muscle weakness and wasting that are initially in a humero-
peroneal distribution and can later extend to the scapular and pelvic girdle muscles.
The progression of muscle wasting is usually slow in the first three decades of life,
after which it becomes more rapid. Loss of ambulation can occur in AD-EDMD, but
is rare in XL-EDMD [Bonne et al 2000].
Cardiac involvement that may include palpitations, presyncope and syncope, poor
exercise tolerance, congestive heart failure, and a variable combination of
supraventricular arrhythmias, disorders of atrioventricular conduction, ventricular
arrhythmias, dilated cardiomyopathy, and sudden death despite pacemakerimplantation [Sanna et al 2003]. Cardiac conduction defects can include sinus
http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2002.726http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2002.726http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.novelli.2002.426http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.novelli.2002.426http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.caux.2003.1006http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.caux.2003.1006http://www.ncbi.nlm.nih.gov/books/n/gene/hgps/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/codon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2003.2055http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.eriksson.2003.293http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.eriksson.2003.293http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.chen.2003.440http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.navarro.2004.2493http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanesch.2006.517http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.renou.2008.666http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001a.1707http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001a.1707http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001b.2747http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001b.2747http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.murase.2002.1017http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.wulff.1997.526http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1998.855http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.felice.2000.275http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.felice.2000.275http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2003.e132http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2003.e132http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.knoblauch.2010.136http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sanna.2003.2227http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-recessive/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2002.726http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.novelli.2002.426http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.novelli.2002.426http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.caux.2003.1006http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.caux.2003.1006http://www.ncbi.nlm.nih.gov/books/n/gene/hgps/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/codon/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.desandregiovannoli.2003.2055http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.eriksson.2003.293http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.eriksson.2003.293http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/autosomal-dominant/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.chen.2003.440http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.navarro.2004.2493http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vanesch.2006.517http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.renou.2008.666http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001a.1707http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001a.1707http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hegele.2001b.2747http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.murase.2002.1017http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.wulff.1997.526http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.manilal.1998.855http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.felice.2000.275http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brown.2001.359http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2003.e132http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.knoblauch.2010.136http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.sanna.2003.22277/30/2019 Emery Dreifuse
10/32
bradycardia, first-degree atrioventricular block, Wenckebach phenomenon, third-
degree atrioventricular block, and bundle-branch block. Atrial arrhythmias
(extrasystoles, atrial fibrillation, flutter) and ventricular arrhythmias (extrasystoles,
ventricular tachycardia) are frequent. In AD-EDMD, the risk of ventricular
tachyarrhythmia and dilated cardiomyopathy manifested by left ventricular dilation
and dysfunction is higher than in XL-EDMD [Bcane et al 2000,Bonne et al 2003,Boriani et al 2003,Draminska et al 2005,Pasotti et al 2008]. Individuals are at risk
for cerebral emboli and sudden death [Boriani et al 2003]. A generalized dilated or
hypertrophic cardiomyopathy often occurs.
Age of onset, severity, and progression of the muscle and cardiac involvement demonstrate
both inter- and intrafamilial variability[Mercuri et al 2000,Mercuri et al 2004,Carboni et al
2010]. Clinical variability ranges from early and severe presentation in childhood to late
onset and a slowly progressive course. In general, joint contractures appear during the first
two decades, followed by muscle weakness and wasting.
Cardiac involvement usually arises after the second decade of life. Respiratory function canbe impaired in some individuals [Emery 2000, Mercuri et al 2000, Ben Yaou et al 2002,
Talkop et al 2002,Mercuri et al 2004,Gueneau et al 2009]. On occasion, sudden cardiac
death is the first manifestation of the disorder [Bcane et al 2000, Karkkainen et al 2004,De
Backer et al 2010].
AR-EDMD. Only one individual with genetically proven AR-EDMD (i.e., homozygous for a
LMNAmutation) has been reported [Raffaele Di Barletta et al 2000]. He had severe muscular
dystrophy. He experienced difficulties when he started walking at age 14 months; at age five
years, contractures prevented him from standing. By age 40 years, he had severe and diffuse
muscle wasting and was confined to a wheelchair. Cardiac evaluation revealed no
abnormalities [Raffaele Di Barletta et al 2000].
Genotype-Phenotype Correlations
EMD. The majority ofEMD mutations are null mutations that result in complete absence of
emerin expression in nuclei; however, intra- and interfamilial variability in the severity of the
phenotype associated with null mutations may be observed [Muntoni et al 1998,
Hoeltzenbein et al 1999,Canki-Klain et al 2000, Ellis et al 2000].
The few missense mutations that have been identified are associated with decreased or
normal amounts of emerin and result in a milderphenotype [Yates et al 1999].
LMNA mutations do not show a clear correlation between genotypeandphenotype [Bonne et
al 2000, Genschel & Schmidt 2000, Bonne et al 2003].
Marked intra- and interfamilial variabilityis observed for the sameLMNAmutation [Bcane
et al 2000,Bonne et al 2000, Mercuri et al 2005, Carboni et al 2010]. For example, within the
same family the same mutation can lead to AD-EDMD, LGMD1B, orisolatedDCM-CD, i.e.,
laminopathies involving striated muscle [Bcane et al 2000,Brodsky et al 2000].
Because only one individual with AR-EDMD and a homozygousp.His222Tyr
mutation ofLMNA has been reported [Raffaele Di Barletta et al 2000], no genotype-phenotype correlations can be made.
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.draminska.2005.207http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.draminska.2005.207http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.pasotti.2008.1250http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/intrafamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/intrafamilial-variability/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2000.1704http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2000.1704http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.emery.2000.228http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2000.1704http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2002.721http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.talkop.2002.878http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.talkop.2002.878http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.karkkainen.2004.885http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.karkkainen.2004.885http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.debacker.2010.97http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.debacker.2010.97http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/interfamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.1998.72http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hoeltzenbein.1999.166http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hoeltzenbein.1999.166http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.cankiklain.2000.389http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ellis.2000.24http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.genschel.2000.451http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/interfamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/interfamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2005.602http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brodsky.2000.473http://www.ncbi.nlm.nih.gov/books/NBK1436/table/edmd.T.selected_lmna_pathologic_allelic_/?report=objectonlyhttp://www.ncbi.nlm.nih.gov/books/NBK1436/table/edmd.T.selected_lmna_pathologic_allelic_/?report=objectonlyhttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.draminska.2005.207http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.pasotti.2008.1250http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.boriani.2003.901http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/intrafamilial-variability/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2000.1704http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.emery.2000.228http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2000.1704http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2002.721http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.talkop.2002.878http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2004.690http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.gueneau.2009.338http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.karkkainen.2004.885http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.debacker.2010.97http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.debacker.2010.97http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/interfamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.1998.72http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hoeltzenbein.1999.166http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.cankiklain.2000.389http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ellis.2000.24http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.yates.1999.159http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.genschel.2000.451http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2003.508http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/interfamilial-variability/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bonne.2000.170http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.mercuri.2005.602http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.carboni.2010.85http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.becane.2000.1661http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.brodsky.2000.473http://www.ncbi.nlm.nih.gov/books/NBK1436/table/edmd.T.selected_lmna_pathologic_allelic_/?report=objectonlyhttp://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/mutation/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.raffaeledibarletta.2000.1407http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/genotype/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/7/30/2019 Emery Dreifuse
11/32
EMD and LMNA. Severe EDMD has been reported in individuals with mutations in both
EMD andLMNA [Muntoni et al 2006]. A range of clinical presentations (i.e. CMT2, CMT2-
EDMD, and isolated cardiomyopathy) were found in a large family in which mutations in
EMD andLMNA genes cosegregate [Ben Yaou et al 2007].
Penetrance
FiveLMNA mutations were reported with incompletepenetrance in families with AD-EDMD
or otherLMNA-related disorders [Vytopil et al 2002,Rankin et al 2008].
Anticipation
Anticipation has not been observed to date.
Prevalence
The overall prevalence of EDMD is not known.
The prevalence of XL-EDMD is estimated at 1:100,000.
HeterozygousLMNA mutations causing AD-EDMD are more common thanEMD mutations
causing XL-EDMD.
Hopkins & Warren [1992] estimated EDMD to be the third most prevalent muscular
dystrophy, with the two dystrophinopathies, Duchenne muscular dystrophy and Becker
muscular dystrophy, being the two most prevalent.
Go to:
Differential Diagnosis
For current information on availability of genetic testing for disorders included in this
section, see GeneTests Laboratory Directory. ED.
Some neuromuscular disorders result in a similar pattern of muscle involvement, joint
contractures, or cardiac disease, but none associates the triad observed in Emery-Dreifuss
muscular dystrophy (EDMD).
Scapulo-peroneal syndromes without contractures or cardiac disease
Facioscapulohumeral muscular dystrophy (FSHD)
Adult-onset scapulo-peroneal myopathy
X-linked scapulo-peroneal muscular dystrophy linked to chromosome 12
[Wilhelmsen et al 1996,Quinzii et al 2008]
Scapulo-peroneal spinal muscle atrophy linked tochromosome 12 [Isozumi et al
1996]
Spinal muscle atrophy of Stark-Kaeser type [Kaeser 1965]
Some forms of hyaline body myopathy [Masuzugawa et al 1997,Onengut et al 2004]
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.2006.1260http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2007.1883http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/penetrance/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/penetrance/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2002.958http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2002.958http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.rankin.2008.1530http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hopkins.1992.1http://www.ncbi.nlm.nih.gov/books/n/gene/dbmd/http://www.ncbi.nlm.nih.gov/books/n/gene/dbmd/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/n/gene/fsh/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.wilhelmsen.1996.507http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.wilhelmsen.1996.507http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quinzii.2008.208http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.isozumi.1996.1377http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.isozumi.1996.1377http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.kaeser.1965.407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.masuzugawa.1997.253http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.masuzugawa.1997.253http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.onengut.2004.4http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.2006.1260http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/isolated/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.benyaou.2007.1883http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/penetrance/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.vytopil.2002.958http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.rankin.2008.1530http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.hopkins.1992.1http://www.ncbi.nlm.nih.gov/books/n/gene/dbmd/http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab?db=GeneTestshttp://www.ncbi.nlm.nih.gov/books/n/gene/fsh/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.wilhelmsen.1996.507http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.quinzii.2008.208http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/chromosome/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.isozumi.1996.1377http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.isozumi.1996.1377http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.kaeser.1965.407http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.masuzugawa.1997.253http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.onengut.2004.47/30/2019 Emery Dreifuse
12/32
Other myopathies with or without contractures and/or cardiac disease that can
resemble AD-EDMD but have distinguishing features
SYNE1 and SYNE2 related EDMD-like [Zhang et al 2007]. The cardiomuscular
features associated with SYNE1 and SYNE2 variants reported in four families were
reminiscent of those observed in EDMD (i.e., mainly cardiac disease) but do not fullyfit with the typical EDMDphenotype [Zhang et al 2007: Supplementary Material].
Rigid spine syndrome [Moghadaszadeh et al 1999], especially selenopathies
[Moghadaszadeh et al 2001,Ferreiro et al 2002]
FKRPgene-related disorders [Poppe et al 2003] (see Congenital Muscular Dystrophy
Overviewand Limb-Girdle Muscular Dystrophy Overview)
Bethlem myopathy caused by collagen VIgenemutations [Bertini & Pepe 2002] (see
Collagen Type VI-Related Disorders)
Myotonic dystrophy type 1
Dystrophinopathies
Limb-girdle muscular dystrophies with cardiac involvement [Muntoni 2003] (see
Limb-Girdle Muscular Dystrophy Overview) Desmin-related myopathies [Goldfarb et al 2004] (see Myofibrillar Myopathy)
X-linked vacuolar myopathies with cardiomyopathy or Danon disease [Danon et al
1981]
Myotonic dystrophy type 2 (proximal myotonic myopathy [PROMM]) [Udd et al
2003]
Myopathy with maltase acid deficiency [Lafort et al 2010]
Other disorders with distinguishing features
Ankylosing spondylitis [Goncu et al 2003]
Go to:
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with Emery-Dreifuss muscular
dystrophy (EDMD), the following evaluations are recommended:
ECG, Holter-ECG monitoring, echocardiography, radionucleotide angiography, and
cardiac MRI. Electrophysiologic study is often advisable in EDMD; however, it is
performed in selected individuals on the basis of the clinical presentation and the
results of noninvasive studies and not as an "evaluation at initial diagnosis" in all
individuals.
Evaluation of respiratory function (vital capacity measurement and other pulmonary
volume measurements)
Evaluation of metabolic functions (glycemia, insulinemia, trigylceridemia)
Treatment of Manifestations
The following are appropriate:
http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.zhang.2007.901http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.zhang.2007.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.moghadaszadeh.1999.376http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.moghadaszadeh.2001.17http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.moghadaszadeh.2001.17http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ferreiro.2002.739http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.poppe.2003.1246http://www.ncbi.nlm.nih.gov/books/n/gene/cmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/cmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/cmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bertini.2002.193http://www.ncbi.nlm.nih.gov/books/n/gene/bethlem/http://www.ncbi.nlm.nih.gov/books/n/gene/myotonic-d/http://www.ncbi.nlm.nih.gov/books/n/gene/dbmd/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.2003.577http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goldfarb.2004.723http://www.ncbi.nlm.nih.gov/books/n/gene/mfm/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.danon.1981.51http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.danon.1981.51http://www.ncbi.nlm.nih.gov/books/n/gene/myotonic-d2/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.udd.2003.589http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.udd.2003.589http://www.ncbi.nlm.nih.gov/books/n/gene/gsd2/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.laforet.2010.128http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goncu.2003.456http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-2http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.zhang.2007.901http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/phenotype/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.zhang.2007.901http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.moghadaszadeh.1999.376http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.moghadaszadeh.2001.17http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.ferreiro.2002.739http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.poppe.2003.1246http://www.ncbi.nlm.nih.gov/books/n/gene/cmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/cmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/n/gene/glossary/def-item/gene/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.bertini.2002.193http://www.ncbi.nlm.nih.gov/books/n/gene/bethlem/http://www.ncbi.nlm.nih.gov/books/n/gene/myotonic-d/http://www.ncbi.nlm.nih.gov/books/n/gene/dbmd/http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.muntoni.2003.577http://www.ncbi.nlm.nih.gov/books/n/gene/lgmd-overview/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goldfarb.2004.723http://www.ncbi.nlm.nih.gov/books/n/gene/mfm/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.danon.1981.51http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.danon.1981.51http://www.ncbi.nlm.nih.gov/books/n/gene/myotonic-d2/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.udd.2003.589http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.udd.2003.589http://www.ncbi.nlm.nih.gov/books/n/gene/gsd2/http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.laforet.2010.128http://www.ncbi.nlm.nih.gov/books/NBK1436/#edmd.REF.goncu.2003.456http://www.ncbi.nlm.nih.gov/books/NBK1436/#ui-ncbiinpagenav-27/30/2019 Emery Dreifuse
13/32
Orthopedic surgeries to release Achilles tendons and other contractures or scoliosis as
needed
Use of mechanical aids (canes, walkers, orthoses, wheelchairs) as needed to help
ambulation
Specific treatments for cardiac features (arrhythmias, AV conduction disorders, and
congestive heart failure), including antiarrhythmic drugs, cardiac pacemaker,implantable cardioverter defibrillator (ICD), and both pharmacologic and non-
pharmacologic therapy for heart failure [Bcane et al 2000,Bonne et al 2003, Boriani
et al 2003]. Heart transplantation may be necessary in the end stages of heart failure;
some individuals may not be candidates for heart transplantation because of
associated severe skeletal muscle and respiratory involvement.
Use of respiratory aids (respiratory muscle training and assisted coughing techniques,
mechanical ventilation) if indicated in late stages
Prevention of Secondary Complications
Physical therapy and stretching exercises promote mobility and help prevent contractures.
When indicated, implantation of cardiac defibrillators can considerably reduce the risk of
sudden death [Meune et al 2006].
Antithromboembolic drugs (vitamin K antagonists, warfarin, heparin) are probably required
to prevent cerebral thromboembolism of cardiac origin in those individuals with either
decreased left ventricular function or atrial arrhythmias [Boriani et al 2003].
Surveillance
The following are appropriate:
Annual cardiac assessment consisting of ECG, Holter monitoring, and
echocardiography in order to detect asymptomatic cardiac disease. More advanced
and invasive cardiac assessment may be required.
Monitoring of respiratory function
Agents/Circumstances to Avoid
Although malignant hyperthermia susceptibilityhas not been described in EDMD, it is
appropriate to anticipate a possible malignant hyperthermia reaction and t