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Emery-Dreifuss Muscular Dystrophy

, PhD, , MD, and , MD.

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Initial Posting: ; Last Update: November 25, 2015.

Estimated reading time: 40 minutes


Clinical characteristics.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the 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.


The three genes in which pathogenic variants are known to cause EDMD are EMD (encoding emerin) and FHL1 (encoding FHL1), which cause X-linked EDMD (XL-EDMD); and LMNA (encoding lamin A and C), which causes autosomal dominant EDMD (AD-EDMD) and autosomal recessive EDMD (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 of EMD or FHL1. The diagnosis of AD-EDMD and AR-EDMD also relies on molecular genetic testing of LMNA.


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 for sudden death.

Prevention of secondary complications: Antithromboembolic drugs to prevent cerebral thromboembolism of cardiac origin in those with decreased left ventricular function or atrial arrhythmias.

Surveillance: At a minimum, 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.

Evaluation 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, or autosomal recessive manner.

  • XL-EDMD. If the mother of a proband has a pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Female carriers are usually asymptomatic, but are at risk of developing a cardiac disease, progressive muscular dystrophy, and/or an EDMD phenotype.
  • AD-EDMD. 65% of probands with AD-EDMD have a de novo LMNA pathogenic variant. Each child of an individual with AD-EDMD has a 50% chance of inheriting the pathogenic variant.
  • 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 pathogenic variant(s) have been identified in a family member.


Suggestive Findings

Emery-Dreifuss muscular dystrophy (EDMD) should be suspected in individuals with 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
    • 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.
    • Dilated or hypertrophic cardiomyopathy may be detected by the performance of echocardiographic evaluation.

Other clinical findings are nonspecific:

Other nonspecific laboratory findings:

  • Serum CK concentration is normal or moderately elevated (2-20x 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 [Fidziańska et al 1998, Sabatelli et al 2001, Sewry et al 2001, Fidziańska & Hausmanowa-Petrusewicz 2003, Fidziańska & Glinka 2007]. Inflammatory changes may also be found in LMNA-related myopathies including EDMD [Komaki et al 2011]. 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 blot in various tissues: exfoliative buccal cells, lymphocytes, lymphoblastoid cell lines, skin biopsy, or muscle biopsy [Manilal et al 1997, Mora et al 1997].
    • In individuals with XL-EDMD, emerin is absent in 95% [Yates & Wehnert 1999].
    • 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 carrier detection because it may show either a normal or a reduced amount of emerin, depending on the proportion of nuclei expressing emerin.
    • 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/or western blot in fresh muscle biopsy or myoblasts, fibroblasts, and cardiomyocytes [Sheikh et al 2008, Gueneau et al 2009].
    • In individuals with FHL1-related XL-EDMD, FHL1 is absent or significantly decreased [Gueneau et al 2009].
    • In female carriers of FHL1-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 due to expression of the wild-type allele at the nuclear membrane and in the nuclear matrix. Western blot analysis for lamin A/C may contribute to the diagnosis, but yields normal results in many affected individuals [Menezes et al 2012].

Note: Diagnosis guidelines have been previously reported [Emery 1989, Yates 1991].

Establishing the Diagnosis

The diagnosis of EDMD is established in a proband with a clearly relevant clinical picture including limb muscle wasting and/or weakness and elbow or neck/spine joint contractures (cardiac disease may be missing in the first decades of life) and with identification of a hemizygous or heterozygous pathogenic variant in one of the genes listed in Table 1.

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

Serial single-gene testing can be devised according to emerin protein status and mode of inheritance:

  • If emerin is absent or reduced (muscle, skin, lymphoblastoid cell lines), EMD should be tested first.
  • If typical clinical presentation AND:
    • Clear X- linked inheritance, EMD should be analyzed first, followed by FHL1.
    • Clear autosomal dominant inheritance, LMNA should be analyzed first.
    • Absence of these clear inheritances, LMNA should be analyzied first, followed by EMD and then FHL1.
    • Affected female who represents a simplex case (i.e., a single occurrence in a family) LMNA should be analyzed before considering analysis of the X-linked genes. Carrier females rarely manifest X-linked EDMD; thus, affected females are much more likely to have AD-EDMD.

Sequence analysis of the gene of interest is performed first, followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found.

A multigene panel that includes EMD, FHL1, LMNA and other genes of interest (see Differential Diagnosis) may also be considered. (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

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

More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if serial single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of EDMD. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Emery-Dreifuss Muscular Dystrophy (EDMD)

Gene 1Proportion of EDMD Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 2 Detected by Test Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
EMD~61% of XL-EDMD 599% 6, 7Unknown 8
FHL1~10% of XL-EDMD 56/7 families 6, 91/7 families 9
LMNA~45% of AD-EDMD 10; unknown for AR-EDMD 1199% 10Unknown 12
Unknown 13NA

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


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


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


Estimates are based on the published experience in France [Gueneau et al 2009].


Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.


Sequencing of EMD (6 exons, 5 short introns, and promoter region) detects a pathogenic variant in EMD in more than 99% of individuals with established X-linked inheritance and/or with no emerin detected by immunodetection methods [Manilal et al 1998].


No systematic data on gene-targeted deletion/duplication analysis detection rate are available; however, large deletions have been reported in six patients [Manilal et al 1998, Small & Warren1998, Fujimoto et al 1999, Ankala et al 2012, Askree et al 2013].


Pathogenic variants in FHL1 were identified in seven families with an established X-linked inheritance or individuals with no or highly reduced FHL1 expression as determined by immunodetection studies of muscle tissue [Gueneau et al 2009].


Sequence analysis of the coding regions of LMNA (12 exons and their flanking intronic regions) detects pathogenic variants in nearly 100% of individuals with LMNA sequence variants (missense and nonsense variants, small deletions/insertions); however, this represents only about 45% of individuals with AD-EDMD because (a) large deletions and duplications involving one or several exons are not detected and (b) other as-yet undiscovered genes could be implicated in AD-EDMD [Bonne et al 2000, Brown et al 2001, Bonne et al 2003, Vytopil et al 2003].


AR-EDMD is very rare. Two homozygous LMNA pathogenic variants leading to AR-EDMD [Raffaele Di Barletta et al 2000, Jimenez-Escrig et al 2012] and four in a compound heterozygous state [Brown et al 2001, Mittelbronn et al 2006, Scharner et al 2011] have been reported. However, some of these pathogenic variants appear to act in a dominant fashion as well [Scharner et al 2011].


Four large deletions have been identified. One encompasses the promoter region and the beginning of exon 1 and is responsible for a neurogenic variant of EDMD [Walter et al 2005]. The three others – deletion of exon 1 [van Tintelen et al 2007], deletion of exons 3 to 12 [Gupta et al 2010], and a complex rearrangement involving a double deletion [Marsman et al 2011] – are responsible for isolated cardiac disease.


About 64% of individuals with a diagnosis of EDMD who have emerin detected on immunocytochemistry and/or immunoblotting have no pathogenic variant identified in EMD, FHL1, or LMNA, suggesting that these individuals are either misdiagnosed or that other, as-yet unidentified genes are involved in EDMD [Gueneau et al 2009]. Pathogenic variants in TMEM43 were reported by Liang et al [2011] in EDMD-like patients, but other genes remain to be identified.

Clinical Characteristics

Clinical Description

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, Bécane et al 2000, Bonne et al 2000, Felice et al 2000, Raffaele Di Barletta et al 2000, Brown et al 2001, Boriani et al 2003, Vytopil et al 2003, Gueneau et al 2009, Knoblauch et al 2010, Cowling et al 2011, Schessl et al 2011].

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 post-cervical 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 pacemaker implantation [Sanna et al 2003]. Cardiac conduction defects can include sinus 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 for ventricular tachyarrhythmia and dilated cardiomyopathy manifested by left ventricular dilation and dysfunction is higher than in XL-EDMD [Bécane 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.

Variability. 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.

Progression. Cardiac involvement usually arises after the second decade of life. Respiratory function can be impaired in some individuals [Emery 2000, Mercuri et al 2000, Talkop et al 2002, Mercuri et al 2004, Ben Yaou et al 2007, Gueneau et al 2009]. On occasion, sudden cardiac death is the first manifestation of the disorder [Bécane et al 2000, Kärkkäinen et al 2004, De Backer et al 2010].

AR-EDMD. Only five individuals with genetically proven isolated AR-EDMD (i.e., homozygous for a LMNA pathogenic variant) have been reported [Raffaele Di Barletta et al 2000, Jimenez-Escrig et al 2012]. From the authors’ non-published data, three additional individuals with EDMD who are homozygous for a LMNA pathogenic variant and eight individuals with compound heterozygous LMNA pathogenic variants were identified. Muscle involvement in these eleven unpublished individuals was generally more severe than in the heterozygous individuals. When evaluated, parents or direct heterozygous relatives were completely asymptomatic. The first reported individual, who had a homozygous c.664C>T LMNA pathogenic variant, initially experienced difficulties when he started walking at age 14 months as a result of severe muscular dystrophy and joint contractures. He was confined to a wheelchair by age 40 years but has had no known cardiac abnormalities [Raffaele Di Barletta et al 2000]. The four other individuals with a homozygous c.674G>A LMNA pathogenic variant belong to a Spanish family, in which one sib [Jimenez-Escrig et al 2012] was incidentally diagnosed with AR-EDMD through exome sequencing. These individuals have severe muscular dystrophy in a limb-girdle distribution with joint contractures leading to ambulation loss in two, at ages 25 and 35 years. Cardiac disease consists mainly of premature atrial and ventricular contractions and conduction defects.

Genotype-Phenotype Correlations

EMD. The majority of EMD pathogenic variants are null variants that result in complete absence of emerin expression in nuclei; however, intra- and interfamilial variability in the severity of the phenotype associated with null variants may be observed [Muntoni et al 1998, Hoeltzenbein et al 1999, Canki-Klain et al 2000, Ellis et al 2000].

The few missense variants that have been identified are associated with decreased or normal amounts of emerin and result in a milder phenotype [Yates et al 1999].

LMNA pathogenic variants do not show a clear genotype/phenotype correlation with regard to EDMD [Bonne et al 2000, Genschel & Schmidt 2000, Bonne et al 2003, Scharner et al 2010, Bertrand et al 2011]. Benedetti et al reported that individuals with early skeletal muscle involvement frequently have pathogenic missense variants, whereas those with later-onset muscle symptoms often have frameshifts, presumably leading to truncated protein or to nonsense-mediated decay [Benedetti et al 2007].

Marked intra- and interfamilial variability is observed for the same LMNA pathogenic variant [Bécane et al 2000, Bonne et al 2000, Mercuri et al 2005, Carboni et al 2010]. For example, within the same family the same pathogenic variant can lead to AD-EDMD, LGMD1B, or isolated DCM-CD (i.e., laminopathies involving striated muscle) [Bécane et al 2000, Brodsky et al 2000].

Homozygous and compound heterozygous LMNA pathogenic variants appear to lead to a more severe muscular phenotype, as three of the five reported individuals with homozygous LMNA pathogenic variants lost ambulation within the third to fifth decades of life [Raffaele Di Barletta et al 2000, Brown et al 2001, Mittelbronn et al 2006, Scharner et al 2011, Jimenez-Escrig et al 2012].

EMD and LMNA. Severe EDMD has been reported in individuals with pathogenic variants in both EMD and LMNA [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 pathogenic variants in EMD and LMNA cosegregate [Ben Yaou et al 2007, Meinke et al 2011].

Modifier gene. A study showed that a possible modifier gene could modulate the age of onset of myopathic symptoms [Granger et al 2011]. Meinke et al identified SUN1 and SUN2 variants in severely affected individuals with LMNA or EMD pathogenic variants [Meinke et al 2014].


Five LMNA pathogenic variants were reported with reduced penetrance in families with AD-EDMD or other LMNA-related disorders [Vytopil et al 2002, Rankin et al 2008].


The overall prevalence of EDMD is not known.

The prevalence of XL-EDMD is estimated at 1:100,000.

Heterozygous LMNA pathogenic variants causing AD-EDMD are more common than EMD pathogenic variants causing XL-EDMD.

Previous studies [Hopkins & Warren 1992] estimated EDMD to be the third most prevalent muscular dystrophy, with the dystrophinopathies Duchenne muscular dystrophy and Becker muscular dystrophy being the two most prevalent. More recently, the prevalence of EDMD was estimated at 0.13:100,000-0.2:100,000 [Norwood et al 2009].

Differential Diagnosis

Some neuromuscular disorders result in a similar pattern of muscle involvement, joint contractures, or cardiac disease, but most do not feature the complete triad observed in Emery-Dreifuss muscular dystrophy (EDMD).

Table 2.

Disorders to Consider in the Differential Diagnosis of Emery-Dreifuss Muscular Dystrophy

Disorder NameGene(s)OMIMMOI 1Clinical Findings
Muscle InvolvementJoint ContracturesCardiac DiseaseDistinguishing Feature(s)
Facioscapulohumeral muscular dystrophyDUX4
AD+++ (scapuloperoneal)Absence of joint contractures & cardiac disease
Other scapuloperoneal syndromes (neurogenic and myopathic types)DES
+++++ (MYH7, DES)Absence of joint contractures (MYH7, DES) & cardiac disease (TRPV4)
SYNE1-related disordersSYNE1612998
AD+++++Unavailable pending description of additional cases
TMEM43-related myopathiesTMEM43614302AD++++ / –+ / –Unavailable pending description of clear phenotype
SUN1-related disordersSUN1607723
AD++++Absence of cardiac disease
Rigid spine syndromeSELENON
602771AR+++++Absence of cardiac disease; early & severe respiratory failure
TTN-related myopathies (see Salih Myopathy, Hereditary Myopathy w/Early Respiratory Failure, Udd Distal Myopathy)TTNAD
+++++++ / –Variably present cardiac disease; severe respiratory involvement; specific muscle pathology
LAMA2-related muscular dystrophyLAMA2AR++++++ / –Leukodystrophy
FKRP-related muscle diseasesFKRPAR++++/ –+ / –Variably present cardiac disease; possible central nervous system involvement
Collagen type VI-related Bethlem myopathyCOL6A1
AD+++++Absence of cardiac disease; specific muscle imaging pattern
Myotonic dystrophy type 1DMPKAD+++++Absence of joint contractures; myotonia
DystrophinopathiesDMDXL+++++Absence of joint contractures & conduction defects / arrhythmias
Limb-girdle muscular dystrophies with cardiac involvement>50 genes 2AR AD+++++Absence of joint contractures
Desmin-related myopathiesDESAD+++++Absence of joint contractures
X-linked vacuolar myopathies with cardiomyopathyLAMP2300257XL+++++Absence of joint contractures
Myotonic dystrophy type 2CNBPAD+++++Absence of joint contractures
Myopathy with maltase acid deficiencyGAAAR+++++ (rare cases)Absence of joint contractures; peculiar muscle pathology
BAG3-related myofibrillar myopathyBAG3AD+++++++Peculiar muscle pathology; peripheral neuropathy
Ankylosing spondylitisAcquired disease++ (spine)+ / –Absence of overt muscle involvement & limb joint contractures

Typical MOI; exceptions occur



Evaluations Following Initial Diagnosis

To establish the extent of disease and needs 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
    Note: 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 joints by a physical therapist or orthopedist to determine need for therapies (physiotherapy, mechanical aids, orthopedic surgeries)
  • For LMNA-linked EDMD: evaluation of metabolic functions (glycemia, insulinemia, trigylceridemia). Rarely, an individual with LMNA-linked EDMD has had an overlapping LMNA phenotype and additional partial lipodystrophy features, thus requiring a careful metabolic assessment [Garg et al 2002, van der Kooi et al 2002].
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

The following are appropriate:

  • 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 [Bécane 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].


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 susceptibility has not been described in EDMD, it is appropriate to anticipate a possible malignant hyperthermia reaction and to avoid triggering agents such as depolarizing muscle relaxants (succinylcholine) and volatile anesthetic drugs (halothane, isoflurane). Other anesthetic precautions have to be considered [Aldwinckle & Carr 2002].

Body weight should be monitored, as affected individuals may be predisposed to obesity.

Evaluation of Relatives at Risk

It is appropriate to evaluate apparently asymptomatic at-risk sibs, parents, and relatives of individuals with EDMD because of the high risk for cardiac complications (including sudden death) associated with LMNA, EMD, and FLH1 pathogenic variants. Evaluation may allow early identification of family members who would benefit from initiation of treatment and preventive measures [Manilal et al 1998, Bécane et al 2000, Canki-Klain et al 2000, Vytopil et al 2002, Boriani et al 2003, Taylor et al 2003, Gueneau et al 2009, Knoblauch et al 2010, Jimenez-Escrig et al 2012]. Evaluations can include:

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

Pregnancy Management

In a woman with EDMD, pregnancy complications may include the development of cardiomyopathy or progression of preexisting cardiomyopathy, preterm delivery, respiratory involvement, cephalopelvic disproportion, and delivery of a low birth-weight infant. Pregnancy management is challenging, with very limited literature addressing the issue. Caesarean section delivery may be required. Referral of an affected pregnant woman to a specialized obstetric unit in close collaboration with a cardiologist is recommended for optimal pregnancy outcome.

Therapies Under Investigation

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

Genetic Counseling

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

Mode of Inheritance

Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked (XL-EDMD), an autosomal dominant (AD-EDMD), or, rarely, an autosomal recessive (AR-EDMD) manner.

Risk to Family Members – XL-EDMD

Parents of a proband

Sibs of a proband. The risk to sibs depends on the genetic status of the mother:

Offspring of a proband. Affected males transmit the EMD or FHL1 pathogenic variant to:

Other family members. The proband's maternal aunts may be at risk of being carriers and the aunt's offspring, depending on their gender, may be at risk of being carriers or of being affected.

Heterozygote (Carrier) Detection

Molecular genetic testing of at-risk female relatives to determine their genetic status is most informative if the EMD or FHL1 pathogenic variant has been identified in the proband.

Note: Females heterozygous for an EMD or FHL1 pathogenic variant are usually asymptomatic, but they are at risk of developing a cardiac disease, a progressive muscular dystrophy, or an EDMD phenotype [Gueneau et al 2009, Knoblauch et al 2010]. (See Evaluation of Relatives at Risk.)

Risk to Family Members – AD-EDMD

Parents of a proband

  • Some individuals diagnosed with AD-EDMD have an affected parent.
  • A proband with AD-EDMD often has the disorder as the result of a de novo LMNA pathogenic variant. Current unpublished data indicate that 65% of pathogenic variants are de novo [Author, personal observation].
  • Recommendations for the evaluation of parents of a proband with an apparent de novo pathogenic variant include molecular genetic testing and clinical evaluation – in particular, cardiac investigations.
  • The family history of some individuals diagnosed with AD-EDMD may appear to be negative because of failure to recognize the disorder in family members, reduced penetrance, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. Therefore, an apparently negative family history cannot be confirmed unless appropriate evaluations (e.g., molecular genetic testing and cardiac evaluation) have been performed on the parents of the proband. (See Evaluation of Relatives at Risk.)
  • If the parent is the individual in whom the pathogenic variant first occurred, s/he may have somatic mosaicism for the variant and may be mildly/minimally affected.

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the proband's parents.
  • If a parent of the proband is affected, the risk to the sibs is 50%.
  • When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.
  • If the LMNA pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism. Germline mosaicism has been reported; its incidence is not known [Bonne et al 1999, Makri et al 2009].

Offspring of a proband. Each child of an individual with AD-EDMD has a 50% chance of inheriting the LMNA pathogenic variant.

Other family members of a proband

  • The risk to other family members depends on the genetic status of the proband's parents.
  • If a parent is affected, his or her family members are at risk.

Risk to Family Members – AR-EDMD

Parents of a proband

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Heterozygotes (carriers) are usually asymptomatic and are not at risk of developing the disorder. In rare cases, late-onset cardiac disease may occur [Jimenez-Escrig et al 2012]. (See Evaluation of Relatives at Risk.)

Offspring of a proband. The offspring of an individual with AR-EDMD are obligate heterozygotes (carriers) for a pathogenic variant in LMNA.

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

Carrier (Heterozygote) Detection

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

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with AD-EDMD has an LMNA pathogenic variant or clinical evidence of the disorder, the LMNA pathogenic variant is likely de novo. However, possible non-medical explanations that could also be explored include alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption.

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.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

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

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the EMD, LMNA, or FHL1 pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for EDMD are possible.


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

  • National Library of Medicine Genetics Home Reference
  • Association Francaise contre les Myopathies (AFM)
    1 Rue de l'International
    Evry cedex 91002
    Phone: +33 01 69 47 28 28
  • European Neuromuscular Centre (ENMC)
    Lt Gen van Heutszlaan 6
    3743 JN Baarn
    Phone: 31 35 5480481
    Fax: 31 35 5480499
  • Muscular Dystrophy Association - USA (MDA)
    222 South Riverside Plaza
    Suite 1500
    Chicago IL 60606
    Phone: 800-572-1717
  • Muscular Dystrophy UK
    61A Great Suffolk Street
    London SE1 0BU
    United Kingdom
    Phone: 0800 652 6352 (toll-free); 020 7803 4800

Molecular Genetics

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

Table B.

OMIM Entries for Emery-Dreifuss Muscular Dystrophy (View All in OMIM)


Molecular Genetic Pathogenesis

Pathogenic variants in three genes are known to cause EDMD. These genes encode ubiquitous proteins localized either in the nuclear membrane or in the cytoplasm and nucleoplasm.

Elucidation of the pathophysiology of Emery-Dreifuss muscular dystrophy (EDMD), caused by pathogenic variants in EMD, LMNA, or FHL1, still requires deciphering of the role of the proteins that they encode in the functional organization of the nuclear envelope.

EMD and FHL1 pathogenic variants cause, in most cases, absence of emerin or FHL1 isoforms [Manilal et al 1998, Gueneau et al 2009]; a few EMD missense or in-frame deletions or insertions lead to aberrant targeting at the inner nuclear membrane and binding of emerin to lamins [Fairley et al 1999]. Missense LMNA pathogenic variants lead to expression of abnormal lamins A/C [Muchir et al 2004], whereas nonsense variants in LMNA result in haploinsufficiency with a decreased amount of normal lamins A/C [Bonne et al 1999, Bécane et al 2000]. Analysis of cells or tissues from affected individuals have demonstrated an abnormal nuclear envelope with increased fragility [Manilal et al 1999, Muchir et al 2004, Reichart et al 2004] as well as chromatin alterations [Ognibene et al 1999, Sabatelli et al 2001, Sewry et al 2001, Fidziańska & Hausmanowa-Petrusewicz 2003, Fidziańska & Glinka 2007].

While hypotheses such as an increased susceptibility to apoptosis [Morris 2000] of muscle cell nuclei cannot be completely ruled out, two mechanisms (not necessarily mutually exclusive) could be involved in EDMD pathogenesis [Broers et al 2006, Worman & Bonne 2007, Worman et al 2009]:

  • Structural mechanisms caused by mechanical stress present in skeletal muscle and cardiac muscle
  • Modification of gene expression relative to abnormal chromatin organization associated with alteration of proliferation/differentiation and/or signaling pathways of muscle cells

Interactions of these nuclear envelope proteins with chromatin- and nuclear matrix-associated proteins are of particular interest. Both emerin and lamin A/C interact with nuclear actin, a component of the chromatin remodeling complex associated with the nuclear matrix, suggesting that either chromatin arrangement or gene transcription or both could be impaired in the disease [Maraldi et al 2002]. Numerous other interactions have been analyzed resulting in identification of transcription factors such as c-fos, pRb, and Lco1 as binding partners of Lamin A/C. These point toward possible deregulation of signaling pathways and alteration of proliferation/differentiation of muscle cells [Broers et al 2006, Vlcek & Foisner 2007, Worman & Bonne 2007, Azibani et al 2014].


Gene structure. The gene has six exons. For a detailed summary of gene and protein information, see Table A, Gene.

Benign variants. Benign variants have been identified.

Pathogenic variants. More than 130 different pathogenic variants have been reported to date. See the UMD-EMD Database. The majority of pathogenic variants (95%) are null variants: nonsense variants, deletions/insertions, and splice site variants that lead to exon skipping, frameshift, and premature arrest of translation and, thus to absence of emerin. A few missense variants and in-frame deletions also exist, leading to decreased expression of emerin or to normal expression of a nonfunctional protein [Ellis et al 1998, Yates et al 1999, Yates & Wehnert 1999, Ellis et al 2000]. Most pathogenic variants are unique to a single family. On occasion, two or three families have the same pathogenic variant. No "hot spot" for pathogenic variants is observed in EMD; pathogenic variants are nearly randomly spread out along the gene. (For more information, see Table A.)

Normal gene product. Emerin is a 254-amino acid serine-rich protein expressed in most tissue. It belongs to a family of type II integral membrane proteins, including lamina-associated protein 2 (LP2; β-thymopoietin) and lamin B receptor. The hydrophobic tail anchors the protein to the inner nuclear membrane and the hydrophilic remainder of the molecule projects into the nucleoplasm, where it interacts with the nuclear lamina [Manilal et al 1996, Yorifuji et al 1997]. Emerin binds directly to lamins A/C and to BAF (BANF1; OMIM 603811), a DNA-bridging protein. This binding requires conserved residues in a central lamin A-binding domain and the N-terminal LEM domain of emerin, respectively [Clements et al 2000, Lee et al 2001]. BAF is required for the assembly of emerin and A-type lamins at the reforming nuclear envelope during telophase of mitosis and may mediate their stability in the subsequent interphase [Haraguchi et al 2001].

Abnormal gene product. In most cases, null variants lead to lack of protein product. In the rare cases in which protein is expressed, either the gene product is lacking the transmembrane domain (in-frame distal deletions) and is not able to target the nuclear membrane and thus is delocalized in the nucleoplasm or cytoplasm, or the abnormal protein is present at the nuclear rim (missense variants) but has weakened interactions with the lamina components [Ellis et al 1999, Fairley et al 1999, Ellis et al 2000].


Gene structure. The gene has eight exons. For a detailed summary of gene and protein information, see Table A, Gene.

Benign variants. Benign variants have been identified.

Pathogenic variants. Of the more than 40 disease-associated variants reported in FHL1, seven have been associated with EDMS [Gueneau et al 2009, Knoblauch et al 2010]. They are localized in the distal exons (5-8) of FHL1: two missense variants affecting highly conserved cysteines, one abolishing the termination codon, and four out-of-frame insertions or deletions [Gueneau et al 2009]. (For more information, see Table A.)

Normal gene product. Three FHL1 isoforms are produced by alternative splicing of FHL1.

FHL1 proteins belong to a protein family containing four and a half LIM domains (Lin-11, Isl-1, Mec3), which are highly conserved sequences comprising two zinc fingers in tandem, implicated in numerous interactions. Each of the two zinc fingers contains four highly conserved cysteines linking together one zinc ion [Kadrmas & Beckerle 2004]. The main isoform FHL1A is predominantly expressed in striated muscles [Lee et al 1998, Taniguchi et al 1998]. The two other (less abundant) isoforms, FHL1B and FHL1C, are expressed in striated muscles [Brown et al 1999, Ng et al 2001]. FHL1A, FHL1B, and FHL1C are, respectively, composed of 4.5, 3.5, and 2.5 LIM domains. Alternative splicing leads to different domains in the C-terminal part of FHL1B and FHL1C, which correspond to nuclear import and export signals in FHL1B and to the RBP-J binding domain in FHL1B and FHL1C [Brown et al 1999, Ng et al 2001]. FHL1A can be localized to the sarcolemma, sarcomere, and nucleus of muscle cells [Brown et al 1999, Ng et al 2001]. It has been implicated in sarcomere assembly by interacting with myosin binding protein-C [McGrath et al 2006].

Abnormal gene product. The pathogenic variants in FHL1 affect the three FHL1 protein isoforms differently since they are located in alternatively spliced exons. The missense variants affect highly conserved cysteine residues important for the zinc finger conformation and lead to variable expression level of mutated protein in muscles of affected individuals. The out-of-frame insertions or deletions give rise to truncated proteins that are expressed in tissues of affected individuals at a very low level. In two individuals for whom myoblasts were available, functional studies demonstrated severe delay in myotube formation [Gueneau et al 2009]. In X-linked myopathy with postural muscle atrophy (XMPMA), pathogenic variants in FHL1 are located in the distal regions of the protein isoforms and were reported to be associated with variable level of FHL1 protein [Windpassinger et al 2008, Schoser et al 2009].


Gene structure. LMNA encodes four transcripts via alternative splicing: two major transcripts: the full-length lamin A (exon 1-12), a shorter transcript lamin C (exon 1-10), and two minor transcripts: lamin A-delta-10 that lacks exon 10 and lamin C2 which has a different N-terminal start (alternative exon 1) from lamin C. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. More than 450 LMNA pathogenic variants are reported to date. See the UMD-LMNA Database [Bonne et al 2003] and Leiden Muscular Dystrophy pages©. The majority (85%) of pathogenic variants are missense variants. Nonsense variants, small deletions/insertions in-frame or with frameshift, and splice-site variants also occur. Pathogenic variants are distributed along the length of the gene [Bonne et al 2000, Brown et al 2001]. A few recurrent pathogenic variants exist [Broers et al 2006]. (For more information, see Table A.)

Table 3.

Selected LMNA Pathogenic Variants

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.664C>Tp.His222Tyr 1NM_005572​.3

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

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.


Normal gene product. Four A-type lamins (A, AΔ10, C, and C2) exist and are products of LMNA by alternative splicing. Lamin A and lamin C are the two main isoforms. They are initially expressed in muscle of the trunk, head, and appendages. Later, they are ubiquitously expressed. However, a few myeloid and lymphoid cell lines have no lamins. Lamin C2 was described in murine and human germ cells [Alsheimer & Benavente 1996]. The promoter 1C2 located in the first intron of LMNA allows transcription of lamin C2. The fourth lamin is lamin AΔ10 (missing exon 10) described in cancer cells [Machiels et al 1996]. Lamins are type-V intermediate filaments that form the nuclear lamina, a fibrous network underlying the inner face of the internal nuclear membrane.

Abnormal gene product. Missense variants (majority of cases) lead to a protein of normal size carrying one modified amino acid. Western blot analysis of fibroblasts of affected individuals demonstrates a normal level of protein expression, strongly suggesting that abnormal proteins are expressed [Muchir et al 2004]. Nonsense variants lead to haploinsufficiency with expression of only the normal allele (~50% of normal protein levels); the mutated allele is either not translated (because of degradation of abnormal mRNA) or is translated and degraded [Bécane et al 2000, Muchir et al 2003]. Pathogenic variants leading to AR disease generally involve different residue changes than those responsible for AD disease. As yet, no clear correlation between the residue change and transmission mode can be drawn, in part due to the rarity of AR disease.


Literature Cited

  • Aldwinckle RJ, Carr AS. The anesthetic management of a patient with Emery-Dreifuss muscular dystrophy for orthopedic surgery. Can J Anaesth. 2002;49:467–70. [PubMed: 11983660]
  • Alsheimer M, Benavente R. Change of karyoskeleton during mammalian spermatogenesis: expression pattern of nuclear lamin C2 and its regulation. Exp Cell Res. 1996;228:181–8. [PubMed: 8912709]
  • Ankala A, Kohn JN, Hegde A, Meka A, Ephrem CL, Askree SH, Bhide S, Hegde MR. Aberrant firing of replication origins potentially explains intragenic nonrecurrent rearrangements within genes, including the human DMD gene. Genome Res. 2012;22:25–34. [PMC free article: PMC3246204] [PubMed: 22090376]
  • Askree SH, Chin EL, Bean LH, Coffee B, Tanner A, Hegde M. Detection limit of intragenic deletions with targeted array comparative genomic hybridization. BMC Genet. 2013;14:116. [PMC free article: PMC4235222] [PubMed: 24304607]
  • Azibani F, Muchir A, Vignier N, Bonne G, Bertrand AT. Striated muscle laminopathies. Semin Cell Dev Biol. 2014;29:107–15. [PubMed: 24440603]
  • Bécane HM, Bonne G, Varnous S, Muchir A, Ortega V, Hammouda EH, Urtizberea JA, Lavergne T, Fardeau M, Eymard B, Weber S, Schwartz K, Duboc D. High incidence of sudden death with conduction system and myocardial disease due to lamins A and C gene mutation. Pacing Clin Electrophysiol. 2000;23:1661–6. [PubMed: 11138304]
  • Ben Yaou R, Toutain A, Arimura T, Demay L, Massart C, Peccate C, Muchir A, Llense S, Deburgrave N, Leturcq F, Litim KE, Rahmoun-Chiali N, Richard P, Babuty D, Recan-Budiartha D, Bonne G. Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism? Neurology. 2007;68:1883–94. [PubMed: 17536044]
  • Benedetti S, Bertini E, Iannaccone S, Angelini C, Trisciani M, Toniolo D, Sferrazza B, Carrera P, Comi G, Ferrari M, Quattrini A, Previtali SC. Dominant LMNA mutations can cause combined muscular dystrophy and peripheral neuropathy. J Neurol Neurosurg Psychiatry. 2005;76:1019–21. [PMC free article: PMC1739728] [PubMed: 15965218]
  • Benedetti S, Menditto I, Degano M, Rodolico C, Merlini L, D'Amico A, Palmucci L, Berardinelli A, Pegoraro E, Trevisan CP, Morandi L, Moroni I, Galluzzi G, Bertini E, Toscano A, Olivè M, Bonne G, Mari F, Caldara R, Fazio R, Mammì I, Carrera P, Toniolo D, Comi G, Quattrini A, Ferrari M, Previtali SC. Phenotypic clustering of lamin A/C mutations in neuromuscular patients. Neurology. 2007;69:1285–92. [PubMed: 17377071]
  • Bertrand AT, Chikhaoui K, Yaou RB, Bonne G. Clinical and genetic heterogeneity in laminopathies. Biochem Soc Trans. 2011;39:1687–92. [PubMed: 22103508]
  • Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994;8:323–7. [PubMed: 7894480]
  • Bonne G, Ben Yaou R, Demay L, Richard P, Eymard B, Urtizberea JA, Duboc D. Clinical analysis of 32 patients carrying R453W LMNA mutation. Neuromuscul Disord. 2002;12:721.
  • Bonne G, Di Barletta MR, Varnous S, Becane HM, Hammouda EH, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea JA, Duboc D, Fardeau M, Toniolo D, Schwartz K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999;21:285–8. [PubMed: 10080180]
  • Bonne G, Mercuri E, Muchir A, Urtizberea A, Becane HM, Recan D, Merlini L, Wehnert M, Boor R, Reuner U, Vorgerd M, Wicklein EM, Eymard B, Duboc D, Penisson-Besnier I, Cuisset JM, Ferrer X, Desguerre I, Lacombe D, Bushby K, Pollitt C, Toniolo D, Fardeau M, Schwartz K, Muntoni F. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol. 2000;48:170–80. [PubMed: 10939567]
  • Bonne G, Yaou RB, Beroud C, Boriani G, Brown S, de Visser M, Duboc D, Ellis J, Hausmanowa-Petrusewicz I, Lattanzi G, Merlini L, Morris G, Muntoni F, Opolski G, Pinto YM, Sangiuolo F, Toniolo D, Trembath R, van Berlo JH, van der Kooi AJ, Wehnert M. 108th ENMC International Workshop, 3rd Workshop of the MYO-CLUSTER project: EUROMEN, 7th International Emery-Dreifuss Muscular Dystrophy (EDMD) Workshop, 13-15 September 2002, Naarden, The Netherlands. Neuromuscul Disord. 2003;13:508–15. [PubMed: 12899879]
  • Boriani G, Gallina M, Merlini L, Bonne G, Toniolo D, Amati S, Biffi M, Martignani C, Frabetti L, Bonvicini M, Rapezzi C, Branzi A. Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study. Stroke. 2003;34:901–8. [PubMed: 12649505]
  • Brodsky GL, Muntoni F, Miocic S, Sinagra G, Sewry C, Mestroni L. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation. 2000;101:473–6. [PubMed: 10662742]
  • Broers JL, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ. Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev. 2006;86:967–1008. [PubMed: 16816143]
  • Brown CA, Lanning RW, McKinney KQ, Salvino AR, Cherniske E, Crowe CA, Darras BT, Gominak S, Greenberg CR, Grosmann C, Heydemann P, Mendell JR, Pober BR, Sasaki T, Shapiro F, Simpson DA, Suchowersky O, Spence JE. Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy. Am J Med Genet. 2001;102:359–67. [PubMed: 11503164]
  • Brown S, McGrath MJ, Ooms LM, Gurung R, Maimone MM, Mitchell CA. Characterization of two isoforms.of the skeletal muscle LIM protein 1, SLIM1. Localization.of SLIM1 at focal adhesions and the isoform slimmer in.the nucleus of myoblasts and cytoplasmof myotubes suggests.distinct roles in the cytoskeleton and in nuclear-cytoplasmic.communication. J. Biol. Chem. 1999;274:27083–91. [PubMed: 10480922]
  • Canki-Klain N, Recan D, Milicic D, Llense S, Leturcq F, Deburgrave N, Kaplan JC, Debevec M, Zurak N. Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy. Croat Med J. 2000;41:389–95. [PubMed: 11063761]
  • Carboni N, Mura M, Mercuri E, Marrosu G, Manzi RC, Cocco E, Nissardi V, Isola F, Mateddu A, Solla E, Maioli MA, Oppo V, Piras R, Marini S, Lai C, Politano L, Marrosu MG. Cardiac and muscle imaging findings in a family with X-linked Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2012;22:152–8. [PubMed: 21993399]
  • Carboni N, Porcu M, Mura M, Cocco E, Marrosu G, Maioli MA, Solla E, Tranquilli S, Orrù P, Marrosu MG. Evolution of the phenotype in a family with an LMNA gene mutation presenting with isolated cardiac involvement. Muscle Nerve. 2010;41:85–91. [PubMed: 19768759]
  • Caux F, Dubosclard E, Lascols O, Buendia B, Chazouilleres O, Cohen A, Courvalin JC, Laroche L, Capeau J, Vigouroux C, Christin-Maitre S. A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab. 2003;88:1006–13. [PubMed: 12629077]
  • Charniot JC, Pascal C, Bouchier C, Sébillon P, Salama J, Duboscq-Bidot L, Peuchmaurd M, Desnos M, Artigou JY, Komajda M. Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype. Hum Mutat. 2003;21:473–81. [PubMed: 12673789]
  • Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J. LMNA mutations in atypical Werner's syndrome. Lancet. 2003;362:440–5. [PubMed: 12927431]
  • Clements L, Manilal S, Love DR, Morris GE. Direct interaction between emerin and lamin A. Biochem Biophys Res Commun. 2000;267:709–14. [PubMed: 10673356]
  • Cowling BS, Cottle DL, Wilding BR, D'Arcy CE, Mitchell CA, McGrath MJ. Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features. Neuromuscul Disord. 2011;21:237–51. [PubMed: 21310615]
  • De Backer J, Van Beeumen K, Loeys B, Duytschaever M. Expanding the phenotype of sudden cardiac death-An unusual presentation of a family with a Lamin A/C mutation. Int J Cardiol. 2010;138:97–9. [PubMed: 18691775]
  • De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Lévy N. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055. [PubMed: 12702809]
  • De Sandre-Giovannoli A, Chaouch M, Kozlov S, Vallat JM, Tazir M, Kassouri N, Szepetowski P, Hammadouche T, Vandenberghe A, Stewart CL, Grid D, Levy N. Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am J Hum Genet. 2002;70:726–36. [PMC free article: PMC384949] [PubMed: 11799477]
  • Decaudain A, Vantyghem MC, Guerci B, Hécart AC, Auclair M, Reznik Y, Narbonne H, Ducluzeau PH, Donadille B, Lebbé C, Béréziat V, Capeau J, Lascols O, Vigouroux C. New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome. J Clin Endocrinol Metab. 2007;92:4835–44. [PubMed: 17711925]
  • Deconinck N, Dion E, Ben Yaou R, Ferreiro A, Eymard B, Briñas L, Payan C, Voit T, Guicheney P, Richard P, Allamand V, Bonne G, Stojkovic T. Differentiating Emery-Dreifuss muscular dystrophy and collagen VI-related myopathies using a specific CT scanner pattern. Neuromuscul Disord. 2010;20:517–23. [PubMed: 20576434]
  • Draminska A, Kuch-Wocial A, Szulc M, Zwolinska A, Styczynski G, Kostrubiec M, Hausmanowa-Petrusewicz I, Pruszczyk P. Echocardiographic assessment of left ventricular morphology and function in patients with Emery-Dreifuss muscular dystrophy. Int J Cardiol. 2005;102:207–10. [PubMed: 15982486]
  • Ellis JA, Brown CA, Tilley LD, Kendrick-Jones J, Spence JE, Yates JR. Two distal mutations in the gene encoding emerin have profoundly different effects on emerin protein expression. Neuromuscul Disord. 2000;10:24–30. [PubMed: 10677860]
  • Ellis JA, Craxton M, Yates JR, Kendrick-Jones J. Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the Emery-Dreifuss muscular dystrophy phenotype. J Cell Sci. 1998;111:781–92. [PubMed: 9472006]
  • Ellis JA, Yates JR, Kendrick-Jones J, Brown CA. Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery-Dreifuss muscular dystrophy. Hum Genet. 1999;104:262–8. [PubMed: 10323252]
  • Emery AE. Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2000;10:228–32. [PubMed: 10838246]
  • Emery AE. Emery-Dreifuss muscular dystrophy and other related disorders. Br Med Bull. 1989;45:772–87. [PubMed: 2688828]
  • Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423:293–8. [PubMed: 12714972]
  • Fairley EA, Kendrick-Jones J, Ellis JA. The Emery-Dreifuss muscular dystrophy phenotype arises from aberrant targeting and binding of emerin at the inner nuclear membrane. J Cell Sci. 1999;112:2571–82. [PubMed: 10393813]
  • Fanin M, Nascimbeni AC, Aurino S, Tasca E, Pegoraro E, Nigro V, Angelini C. Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes. Neurology. 2009;72:1432–5. [PubMed: 19380703]
  • Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J, Vidaillet HJ Jr, Spudich S, De Girolami U, Seidman JG, Seidman C, Muntoni F, Muehle G, Johnson W, McDonough B. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999;341:1715–24. [PubMed: 10580070]
  • Felice KJ, Schwartz RC, Brown CA, Leicher CR, Grunnet ML. Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene. Neurology. 2000;55:275–80. [PubMed: 10908904]
  • Fidziańska A, Glinka Z. Nuclear architecture remodelling in envelopathies. Folia Neuropathol. 2007;45:47–55. [PubMed: 17594594]
  • Fidziańska A, Hausmanowa-Petrusewicz I. Architectural abnormalities in muscle nuclei. Ultrastructural differences between X-linked and autosomal dominant forms of EDMD. J Neurol Sci. 2003;210:47–51. [PubMed: 12736087]
  • Fidziańska A, Toniolo D, Hausmanowa-Petrusewicz I. Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD). J Neurol Sci. 1998;159:88–93. [PubMed: 9700709]
  • Forissier JF, Bonne G, Bouchier C, Duboscq-Bidot L, Richard P, Wisnewski C, Briault S, Moraine C, Dubourg O, Schwartz K, Komajda M. Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation. Eur J Heart Fail. 2003;5:821–5. [PubMed: 14675861]
  • Friedrich FW, Wilding BR, Reischmann S, Crocini C, Lang P, Charron P, Müller OJ, McGrath MJ, Vollert I, Hansen A, Linke WA, Hengstenberg C, Bonne G, Morner S, Wichter T, Madeira H, Arbustini E, Eschenhagen T, Mitchell CA, Isnard R, Carrier L. Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. Hum Mol Genet. 2012;21:3237–54. [PubMed: 22523091]
  • Fujimoto S, Ishikawa T, Saito M, Wada Y, Wada I, Arahata K, Nonaka I. Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion. Neuropediatrics. 1999;30:161–3. [PubMed: 10480214]
  • Garg A, Speckman RA, Bowcock AM. Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene. Am J Med. 2002;112:549–55. [PubMed: 12015247]
  • Genschel J, Schmidt HH. Mutations in the LMNA gene encoding lamin A/C. Hum Mutat. 2000;16:451–9. [PubMed: 11102973]
  • Goizet C, Ben Yaou R, Demay L, Richard P, Bouillot S, Rouanet M, Hermosilla E, Le Masson G, Lagueny A, Bonne G, Ferrer X. A new mutation of lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease and leukonychia. J Med Genet. 2004;41:e29. [PMC free article: PMC1735710] [PubMed: 14985400]
  • Granger B, Gueneau L, Drouin-Garraud V, Pedergnana V, Gagnon F, Ben Yaou R, Tezenas du Montcel S, Bonne G. Modifier locus of the skeletal muscle involvement in Emery-Dreifuss muscular dystrophy. Hum Genet. 2011;129:149–59. [PubMed: 21063730]
  • Graux P, Carlioz R, Krivosic I, Mekerke W, Camilleri G, Dutoit A, Croccel L. Ann Cardiol Angeiol (Paris). 1993;42:554–60. [Emery-Dreifuss muscular dystrophy with major conduction disorders and cardiac excitability] [PubMed: 8117051]
  • Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, Hoeltzenbein M, Spuler S, Saitoh S, Verschueren A, Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T, Eymard B, Ben Yaou R, Bonne G. Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2009;85:338–53. [PMC free article: PMC2771595] [PubMed: 19716112]
  • Gupta P, Bilinska ZT, Sylvius N, Boudreau E, Veinot JP, Labib S, Bolongo PM, Hamza A, Jackson T, Ploski R, Walski M, Grzybowski J, Walczak E, Religa G, Fidzianska A, Tesson F. Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption. Basic Res Cardiol. 2010;105:365–77. [PMC free article: PMC3934843] [PubMed: 20127487]
  • Haraguchi T, Koujin T, Segura-Totten M, Lee KK, Matsuoka Y, Yoneda Y, Wilson KL, Hiraoka Y. BAF is required for emerin assembly into the reforming nuclear envelope. J Cell Sci. 2001;114:4575–85. [PubMed: 11792822]
  • Hermida-Prieto M, Monserrat L, Castro-Beiras A, Laredo R, Soler R, Peteiro J, Rodriguez E, Bouzas B, Alvarez N, Muniz J, Crespo-Leiro M. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol. 2004;94:50–4. [PubMed: 15219508]
  • Hoeltzenbein M, Karow T, Zeller JA, Warzok R, Wulff K, Zschiesche M, Herrmann FH, Grosse-Heitmeyer W, Wehnert MS. Severe clinical expression in X-linked Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 1999;9:166–70. [PubMed: 10382910]
  • Hopkins LC, Jackson JA, Elsas LJ. Emery-dreifuss humeroperoneal muscular dystrophy: an x-linked myopathy with unusual contractures and bradycardia. Ann Neurol. 1981;10:230–7. [PubMed: 7294729]
  • Hopkins LC, Warren S. Emery-Dreifuss muscular dystrophy. In: Rowland LP, DiMauro D, eds. Handbook of Clinical Neurology: Myopathies. Amsterdam, Netherlands: Elsevier Science; 1992:145-60.
  • Jimenez-Escrig A, Gobernado I, Garcia-Villanueva M, Sanchez-Herranz A. Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing. Muscle Nerve. 2012;45:605–10. [PubMed: 22431096]
  • Kadrmas JL, Beckerle MC. The LIM domain: from the cytoskeleton to the nucleus. Nat Rev Mol Cell Biol. 2004;5:920–31. [PubMed: 15520811]
  • Kärkkäinen S, Helio T, Miettinen R, Tuomainen P, Peltola P, Rummukainen J, Ylitalo K, Kaartinen M, Kuusisto J, Toivonen L, Nieminen MS, Laakso M, Peuhkurinen K. A novel mutation, Ser143Pro, in the lamin A/C gene is common in finnish patients with familial dilated cardiomyopathy. Eur Heart J. 2004;25:885–93. [PubMed: 15140538]
  • Karst ML, Herron KJ, Olson TM. X-linked non-syndromic sinus node dysfunction and atrial fibrillation caused by emerin mutation. J Cardiovasc Electrophysiol. 2008;19:510–5. [PMC free article: PMC2367157] [PubMed: 18266676]
  • Knoblauch H, Geier C, Adams S, Budde B, Rudolph A, Zacharias U, Schulz-Menger J, Spuler A, Yaou RB, Nürnberg P, Voit T, Bonne G, Spuler S. Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation. Ann Neurol. 2010;67:136–40. [PubMed: 20186852]
  • Komaki H, Hayashi YK, Tsuburaya R, Sugie K, Kato M, Nagai T, Imataka G, Suzuki S, Saitoh S, Asahina N, Honke K, Higuchi Y, Sakuma H, Saito Y, Nakagawa E, Sugai K, Sasaki M, Nonaka I, Nishino I. Inflammatory changes in infantile-onset LMNA-associated myopathy. Neuromuscul Disord. 2011;21:563–8. [PubMed: 21632249]
  • Lee KK, Haraguchi T, Lee RS, Koujin T, Hiraoka Y, Wilson KL. Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF. J Cell Sci. 2001;114:4567–73. [PubMed: 11792821]
  • Lee SM, Tsui SK, Chan KK, Garcia-Barcelo M, Wayne MM, Fung KP, Liew CC, Lee CY. Chromosomal.mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1). Gene. 1998;216:163–70. [PubMed: 9714789]
  • Liang WC, Mitsuhashi H, Keduka E, Nonaka I, Noguchi S, Nishino I, Hayashi YK. TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy. Ann Neurol. 2011;69:1005–13. [PubMed: 21391237]
  • Machiels BM, Zorenc AH, Endert JM, Kuijpers HJ, van Eys GJ, Ramaekers FC, Broers JL. An alternative splicing product of the lamin A/C gene lacks exon 10. J Biol Chem. 1996;271:9249–53. [PubMed: 8621584]
  • Makri S, Clarke NF, Richard P, Maugenre S, Demay L, Bonne G, Guicheney P. Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy. Neuromuscul Disord. 2009;19:26–8. [PubMed: 19084400]
  • Manilal S, Nguyen TM, Sewry CA, Morris GE. The Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane protein. Hum Mol Genet. 1996;5:801–8. [PubMed: 8776595]
  • Manilal S, Recan D, Sewry CA, Hoeltzenbein M, Llense S, Leturcq F, Deburgrave N, Barbot J, Man N, Muntoni F, Wehnert M, Kaplan J, Morris GE. Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression. Hum Mol Genet. 1998;7:855–64. [PubMed: 9536090]
  • Manilal S, Sewry CA, Man N, Muntoni F, Morris GE. Diagnosis of X-linked Emery-Dreifuss muscular dystrophy by protein analysis of leucocytes and skin with monoclonal antibodies. Neuromuscul Disord. 1997;7:63–6. [PubMed: 9132142]
  • Manilal S, Sewry CA, Pereboev A, Man N, Gobbi P, Hawkes S, Love DR, Morris GE. Distribution of emerin and lamins in the heart and implications for Emery-Dreifuss muscular dystrophy. Hum Mol Genet. 1999;8:353–9. [PubMed: 9949197]
  • Maraldi NM, Lattanzi G, Sabatelli P, Ognibene A, Squarzoni S. Functional domains of the nucleus: implications for Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:815–23. [PubMed: 12398831]
  • Marsman RF, Bardai A, Postma AV, Res JC, Koopmann TT, Beekman L, van der Wal AC, Pinto YM, Lekanne Deprez RH, Wilde AA, Jordaens LJ, Bezzina CR. A complex double deletion in LMNA underlies progressive cardiac conduction disease, atrial arrhythmias, and sudden death. Circ Cardiovasc Genet. 2011;4:280–7. [PubMed: 21406687]
  • McGrath MJ, Cottle DL, Nguyen MA, Dyson JM, Coghill ID, Robinson PA, Holdsworth M, Cowling BS, Hardeman EC, Mitchell CA, Brown S. Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin filament formation and sarcomere assembly. J Biol Chem. 2006;281:7666–83. [PubMed: 16407297]
  • Meinke P, Mattioli E, Haque F, Antoku S, Columbaro M, Straatman KR, Worman HJ, Gundersen GG, Lattanzi G, Wehnert M, Shackleton S. Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization. PLoS Genet. 2014;10:e1004605. [PMC free article: PMC4161305] [PubMed: 25210889]
  • Meinke P, Nguyen TD, Wehnert MS. The LINC complex and human disease. Biochem Soc Trans. 2011;39:1693–7. [PubMed: 22103509]
  • Menezes MP, Waddell LB, Evesson FJ, Cooper S, Webster R, Jones K, Mowat D, Kiernan MC, Johnston HM, Corbett A, Harbord M, North KN, Clarke NF. Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy. Neurology. 2012;78:1258–63. [PubMed: 22491857]
  • Mercuri E, Brown SC, Nihoyannopoulos P, Poulton J, Kinali M, Richard P, Piercy RJ, Messina S, Sewry C, Burke MM, McKenna W, Bonne G, Muntoni F. Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene. Muscle Nerve. 2005;31:602–9. [PubMed: 15770669]
  • Mercuri E, Counsell S, Allsop J, Jungbluth H, Kinali M, Bonne G, Schwartz K, Bydder G, Dubowitz V, Muntoni F. Selective muscle involvement on magnetic resonance imaging in autosomal dominant Emery-Dreifuss muscular dystrophy. Neuropediatrics. 2002;33:10–4. [PubMed: 11930270]
  • Mercuri E, Manzur AY, Jungbluth H, Bonne G, Muchir A, Sewry C, Schwartz K, Muntoni F. Early and severe presentation of autosomal dominant Emery-Dreifuss muscular dystrophy (EMD2). Neurology. 2000;54:1704–5. [PubMed: 10762524]
  • Mercuri E, Poppe M, Quinlivan R, Messina S, Kinali M, Demay L, Bourke J, Richard P, Sewry C, Pike M, Bonne G, Muntoni F, Bushby K. Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant. Arch Neurol. 2004;61:690–4. [PubMed: 15148145]
  • Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM, Duboc D. Primary prevention of sudden death in patients with lamin A/C gene mutations. N Engl J Med. 2006;354:209–10. [PubMed: 16407522]
  • Mittelbronn M, Hanisch F, Gleichmann M, Stötter M, Korinthenberg R, Wehnert M, Bonne G, Rudnik-Schöneborn S, Bornemann A. Myofiber degeneration in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B). Brain Pathol. 2006;2006;16:266–72. [PubMed: 17107595]
  • Mora M, Cartegni L, Di Blasi C, Barresi R, Bione S, Raffaele di Barletta M, Morandi L, Merlini L, Nigro V, Politano L, Donati MA, Cornelio F, Cobianchi F, Toniolo D. X-linked Emery-Dreifuss muscular dystrophy can be diagnosed from skin biopsy or blood sample. Ann Neurol. 1997;42:249–53. [PubMed: 9266737]
  • Morris GE. Nuclear proteins and cell death in inherited neuromuscular disease. Neuromuscul Disord. 2000;10:217–27. [PubMed: 10838245]
  • Muchir A, Bonne G, van der Kooi AJ, van Meegen M, Baas F, Bolhuis PA, de Visser M, Schwartz K. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet. 2000;9:1453–9. [PubMed: 10814726]
  • Muchir A, Medioni J, Laluc M, Massart C, Arimura T, Kooi AJ, Desguerre I, Mayer M, Ferrer X, Briault S, Hirano M, Worman HJ, Mallet A, Wehnert M, Schwartz K, Bonne G. Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations. Muscle Nerve. 2004;30:444. [PubMed: 15372542]
  • Muchir A, van Engelen BG, Lammens M, Mislow JM, McNally E, Schwartz K, Bonne G. Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp Cell Res. 2003;291:352–62. [PubMed: 14644157]
  • Muntoni F, Bonne G, Goldfarb LG, Mercuri E, Piercy RJ, Burke M, Yaou RB, Richard P, Recan D, Shatunov A, Sewry CA, Brown SC. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain. 2006;129:1260–8. [PubMed: 16585054]
  • Muntoni F, Lichtarowicz-Krynska EJ, Sewry CA, Manilal S, Recan D, Llense S, Taylor J, Morris GE, Dubowitz V. Early presentation of X-linked Emery-Dreifuss muscular dystrophy resembling limb-girdle muscular dystrophy. Neuromuscul Disord. 1998;8:72–6. [PubMed: 9608559]
  • Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Geneviève D, Hadj-Rabia S, Gaudy-Marqueste C, Smitt HS, Vabres P, Faivre L, Verloes A, Van Essen T, Flori E, Hennekam R, Beemer FA, Laurent N, Le Merrer M, Cau P, Lévy N. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet. 2004;13:2493–503. [PubMed: 15317753]
  • Ng EK, Lee SM, Li HY, Ngai SM, Tsui SK, Waye MM, Lee CY, Fung KP. Characterization of tissuespecific.LIM domain protein (FHL1C) which is an alternatively.spliced isoform of a human LIM-only protein (FHL1). J Cell Biochem. 2001;82:1–10. [PubMed: 11400158]
  • Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. 2009;132:3175–86. [PMC free article: PMC4038491] [PubMed: 19767415]
  • Novelli G, Muchir A, Sangiuolo F, Helbling-Leclerc A, D'Apice MR, Massart C, Capon F, Sbraccia P, Federici M, Lauro R, Tudisco C, Pallotta R, Scarano G, Dallapiccola B, Merlini L, Bonne G. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet. 2002;71:426–31. [PMC free article: PMC379176] [PubMed: 12075506]
  • Ognibene A, Sabatelli P, Petrini S, Squarzoni S, Riccio M, Santi S, Villanova M, Palmeri S, Merlini L, Maraldi NM. Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. Muscle Nerve. 1999;22:864–9. [PubMed: 10398203]
  • Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A, Mannarino S, Gambarin F, Favalli V, Grasso M, Agozzino M, Campana C, Gavazzi A, Febo O, Marini M, Landolina M, Mortara A, Piccolo G, Viganò M, Tavazzi L, Arbustini E. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008;52:1250–60. [PubMed: 18926329]
  • Quarta G, Syrris P, Ashworth M, Jenkins S, Zuborne Alapi K, Morgan J, Muir A, Pantazis A, McKenna WJ, Elliott PM. Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2012;33:1128–36. [PubMed: 22199124]
  • Quijano-Roy S, Mbieleu B, Bönnemann CG, Jeannet PY, Colomer J, Clarke NF, Cuisset JM, Roper H, De Meirleir L, D'Amico A, Ben Yaou R, Nascimento A, Barois A, Demay L, Bertini E, Ferreiro A, Sewry CA, Romero NB, Ryan M, Muntoni F, Guicheney P, Richard P, Bonne G, Estournet B. De novo LMNA mutations cause a new form of Congenital Muscular Dystrophy (L-CMD). Ann Neurol. 2008;64:177–86. [PubMed: 18551513]
  • Quinzii CM, Vu TH, Min KC, Tanji K, Barral S, Grewal RP, Kattah A, Camaño P, Otaegui D, Kunimatsu T, Blake DM, Wilhelmsen KC, Rowland LP, Hays AP, Bonilla E, Hirano M. X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet. 2008;82:208–13. [PMC free article: PMC2253963] [PubMed: 18179901]
  • Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, Romorini A, Voit T, Orstavik KH, Merlini L, Trevisan C, Biancalana V, Housmanowa-Petrusewicz I, Bione S, Ricotti R, Schwartz K, Bonne G, Toniolo D. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2000;66:1407–12. [PMC free article: PMC1288205] [PubMed: 10739764]
  • Rankin J, Auer-Grumbach M, Bagg W, Colclough K, Nguyen TD, Fenton-May J, Hattersley A, Hudson J, Jardine P, Josifova D, Longman C, McWilliam R, Owen K, Walker M, Wehnert M, Ellard S. Extreme phenotypic diversity and onpenetrance in families with the LMNA gene mutation R644C. Am J Med Genet A. 2008;146A:1530–42. [PubMed: 18478590]
  • Reichart B, Klafke RS, Dreger C, Kruger E, Motsch I, Ewald A, Schafer J, Reichmann H, Muller CR, Dabauvalle MC. Expression and localization of nuclear proteins in autosomal-dominant Emery-Dreifuss muscular dystrophy with LMNA R377H mutation. BMC Cell Biol. 2004;5:12. [PMC free article: PMC407848] [PubMed: 15053843]
  • Renou L, Stora S, Yaou RB, Volk M, Sinkovec M, Demay L, Richard P, Peterlin B, Bonne G. Heart-hand syndrome of Slovenian type: a new kind of laminopathy. J Med Genet. 2008;45:666–71. [PubMed: 18611980]
  • Sabatelli P, Lattanzi G, Ognibene A, Columbaro M, Capanni C, Merlini L, Maraldi NM, Squarzoni S. Nuclear alterations in autosomal-dominant Emery-Dreifuss muscular dystrophy. Muscle Nerve. 2001;24:826–9. [PubMed: 11360268]
  • Sanna T, Dello Russo A, Toniolo D, Vytopil M, Pelargonio G, De Martino G, Ricci E, Silvestri G, Giglio V, Messano L, Zachara E, Bellocci F. Cardiac features of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene mutations. Eur Heart J. 2003;24:2227–36. [PubMed: 14659775]
  • Scharner J, Brown CA, Bower M, Iannaccone ST, Khatri IA, Escolar D, Gordon E, Felice K, Crowe CA, Grosmann C, Meriggioli MN, Asamoah A, Gordon O, Gnocchi VF, Ellis JA, Mendell JR, Zammit PS. Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations. Hum Mutat. 2011;32:152–67. [PubMed: 20848652]
  • Scharner J, Gnocchi VF, Ellis JA, Zammit PS. Genotype-phenotype correlations in laminopathies: how does fate translate? Biochem Soc Trans. 2010;38:257–62. [PubMed: 20074070]
  • Schessl J, Feldkirchner S, Kubny C, Schoser B. Reducing body myopathy and other FHL1-related muscular disorders. Semin Pediatr Neurol. 2011;18:257–63. [PubMed: 22172421]
  • Schessl J, Zou Y, McGrath MJ, Cowling BS, Maiti B, Chin SS, Sewry C, Battini R, Hu Y, Cottle DL, Rosenblatt M, Spruce L, Ganguly A, Kirschner J, Judkins AR, Golden JA, Goebel HH, Muntoni F, Flanigan KM, Mitchell CA, Bönnemann CG. Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy. J Clin Invest. 2008;118:904–12. [PMC free article: PMC2242623] [PubMed: 18274675]
  • Schoser B, Goebel HH, Janisch I, Quasthoff S, Rother J, Bergmann M, Müller-Felber W, Windpassinger C. Consequences of mutations within the C terminus of the FHL1 gene. Neurology. 2009;73:543–51. [PubMed: 19687455]
  • Sébillon P, Bouchier C, Bidot LD, Bonne G, Ahamed K, Charron P, Drouin-Garraud V, Millaire A, Desrumeaux G, Benaiche A, Charniot JC, Schwartz K, Villard E, Komajda M. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations. J Med Genet. 2003;40:560–7. [PMC free article: PMC1735561] [PubMed: 12920062]
  • Sewry CA, Brown SC, Mercuri E, Bonne G, Feng L, Camici G, Morris GE, Muntoni F. Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations. Neuropathol Appl Neurobiol. 2001;27:281–90. [PubMed: 11532159]
  • Shackleton S, Lloyd DJ, Jackson SN, Evans R, Niermeijer MF, Singh BM, Schmidt H, Brabant G, Kumar S, Durrington PN, Gregory S, O'Rahilly S, Trembath RC. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000;24:153–6. [PubMed: 10655060]
  • Shalaby S, Hayashi YK, Goto K, Ogawa M, Nonaka I, Noguchi S, Nishino I. Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1). Neuromuscul. Disord. 2008;18:959–61. [PubMed: 18952429]
  • Sheikh F, Raskin A, Chu PH, Lange S, Domenighetti AA, Zheng M, Liang X, Zhang T, Yajima T, Gu Y, Dalton ND, Mahata SK, Dorn GW 2nd, Heller-Brown J, Peterson KL, Omens JH, McCulloch AD, Chen J. An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. J. Clin. Invest. 2008;118:3870–80. [PMC free article: PMC2575833] [PubMed: 19033658]
  • Small K, Warren ST. Emerin deletions occurring on both Xq28 inversion backgrounds. Hum Mol Genet. 1998;7:135–9. [PubMed: 9384614]
  • Talkop UA, Talvik I, Sonajalg M, Sibul H, Kolk A, Piirsoo A, Warzok R, Wulff K, Wehnert MS, Talvik T. Early onset of cardiomyopathy in two brothers with X-linked Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:878–81. [PubMed: 12398842]
  • Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T. LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Mol Cell Biol. 1998;18:644–54. [PMC free article: PMC121531] [PubMed: 9418910]
  • Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek MM, Lascor J, Moss AC, Li WL, Stetler GL, Muntoni F, Bristow MR, Mestroni L. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J Am Coll Cardiol. 2003;41:771–80. [PubMed: 12628721]
  • Ura S, Hayashi YK, Goto K, Astejada MN, Murakami T, Nagato M, Ohta S, Daimon Y, Takekawa H, Hirata K, Nonaka I, Noguchi S, Nishino I. Limb-girdle muscular dystrophy due to emerin gene mutations. Arch Neurol. 2007;64:1038–41. [PubMed: 17620497]
  • van Berlo JH, de Voogt WG, van der Kooi AJ, van Tintelen JP, Bonne G, Yaou RB, Duboc D, Rossenbacker T, Heidbuchel H, de Visser M, Crijns HJ, Pinto YM. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med. 2005;83:79–83. [PubMed: 15551023]
  • van der Kooi AJ, Bonne G, Eymard B, Duboc D, Talim B, Van der Valk M, Reiss P, Richard P, Demay L, Merlini L, Schwartz K, Busch HF, de Visser M. Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Neurology. 2002;59:620–3. [PubMed: 12196663]
  • van der Kooi AJ, Ledderhof TM, de Voogt WG, Res CJ, Bouwsma G, Troost D, Busch HF, Becker AE, de Visser M. A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement. Ann Neurol. 1996;39:636–42. [PubMed: 8619549]
  • Van Esch H, Agarwal AK, Debeer P, Fryns JP, Garg A. A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features. J Clin Endocrinol Metab. 2006;91:517–21. [PubMed: 16278265]
  • van Tintelen JP, Tio RA, Kerstjens-Frederikse WS, van Berlo JH, Boven LG, Suurmeijer AJ, White SJ, den Dunnen JT, te Meerman GJ, Vos YJ, van der Hout AH, Osinga J, van den Berg MP, van Veldhuisen DJ, Buys CH, Hofstra RM, Pinto YM. Severe myocardial fibrosis caused by a deletion of the 5' end of the lamin A/C gene. J Am Coll Cardiol. 2007;49:2430–9. [PubMed: 17599607]
  • Vlcek S, Foisner R. A-type lamin networks in light of laminopathic diseases. Biochim Biophys Acta. 2007;1773:661–74. [PubMed: 16934891]
  • Vytopil M, Benedetti S, Ricci E, Galluzzi G, Dello Russo A, Merlini L, Boriani G, Gallina M, Morandi L, Politano L, Moggio M, Chiveri L, Hausmanova-Petrusewicz I, Ricotti R, Vohanka S, Toman J, Toniolo D. Mutation analysis of the lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes. J Med Genet. 2003;40:e132. [PMC free article: PMC1735334] [PubMed: 14684700]
  • Vytopil M, Ricci E, Dello Russo A, Hanisch F, Neudecker S, Zierz S, Ricotti R, Demay L, Richard P, Wehnert M, Bonne G, Merlini L, Toniolo D. Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:958–63. [PubMed: 12467752]
  • Walter MC, Witt TN, Weigel BS, Reilich P, Richard P, Pongratz D, Bonne G, Wehnert MS, Lochmuller H. Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2005;15:40–4. [PubMed: 15639119]
  • Windpassinger C, Schoser B, Straub V, Hochmeister S, Noor A, Lohberger B, Farra N, Petek E, Schwarzbraun T, Ofner L. An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1. Am J Hum Genet. 2008;82:88–99. [PMC free article: PMC2253986] [PubMed: 18179888]
  • Witt TN, Garner CG, Pongratz D, Baur X. Autosomal dominant Emery-Dreifuss syndrome: evidence of a neurogenic variant of the disease. Eur Arch Psychiatry Neurol Sci. 1988;237:230–6. [PubMed: 3203701]
  • Worman HJ, Bonne G. "Laminopathies": a wide spectrum of human diseases. Exp Cell Res. 2007;313:2121–33. [PMC free article: PMC2964355] [PubMed: 17467691]
  • Worman HJ, Fong LG, Muchir A, Young SG. Laminopathies and the long strange trip from basic cell biology to therapy. J Clin Invest. 2009;119:1825–36. [PMC free article: PMC2701866] [PubMed: 19587457]
  • Wulff K, Parrish JE, Herrmann FH, Wehnert M. Six novel mutations in the emerin gene causing X-linked Emery-Dreifuss muscular dystrophy. Hum Mutat. 1997;9:526–30. [PubMed: 9195226]
  • Yates JR, Bagshaw J, Aksmanovic VM, Coomber E, McMahon R, Whittaker JL, Morrison PJ, Kendrick-Jones J, Ellis JA. Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype. Neuromuscul Disord. 1999;9:159–65. [PubMed: 10382909]
  • Yates JR, Wehnert M. The Emery-Dreifuss Muscular Dystrophy Mutation Database. Neuromuscul Disord. 1999;9:199. [PubMed: 10382916]
  • Yates JR. European workshop on Emery-Dreifuss muscular dystrophy 1991. Neuromuscul Disord. 1991;1:393–6. [PubMed: 1822351]
  • Yorifuji H, Tadano Y, Tsuchiya Y, Ogawa M, Goto K, Umetani A, Asaka Y, Arahata K. Emerin, deficiency of which causes Emery-Dreifuss muscular dystrophy, is localized at the inner nuclear membrane. Neurogenetics. 1997;1:135–40. [PubMed: 10732816]
  • Young J, Morbois-Trabut L, Couzinet B, Lascols O, Dion E, Béréziat V, Fève B, Richard I, Capeau J, Chanson P, Vigouroux C. Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes. 2005;54:1873–8. [PubMed: 15919811]

Suggested Reading

  • Ben Yaou R, Gueneau L, Demay L, Stora S, Chikhaoui K, Richard P, Bonne G. Heart involvement in lamin A/C related diseases. Arch Mal Coeur Vaiss. 2006;99:848–55. [PubMed: 17067107]
  • Ben Yaou R, Muchir A, Arimura T, Massart C, Demay L, Richard P, Bonne G. Genetics of laminopathies. Novartis Found Symp. 2005;264:81–90. [PubMed: 15773749]
  • Bonne G, Lampe AK. Muscle diseases with prominent muscle contractures. In: Karpati G, Hilton-Jones D, Griggs RC, Bushby K, eds. Disorders of Voluntary Muscle. 8 ed. Cambridge, UK: Cambridge University Press; 2010:299-313.
  • Decostre V, Ben Yaou R, Bonne G. Laminopathies affecting skeletal and cardiac muscles: clinical and pathophysiological aspects. Acta Myol. 2005;24:104–9. [PubMed: 16550926]
  • Gruenbaum Y, Margalit A, Goldman RD, Shumaker DK, Wilson KL. The nuclear lamina comes of age. Nat Rev Mol Cell Biol. 2005;6:21–31. [PubMed: 15688064]
  • Worman HJ, Ostlund C, Wang Y. Diseases of the nuclear envelope. Cold Spring Harb Perspect Biol. 2010;2:a000760. [PMC free article: PMC2828284] [PubMed: 20182615]

Chapter Notes


The authors are coordinators (GB, FL) or members (RBY) of the French networks for rare diseases on "EDMD and other nuclear envelope pathologies," network supported by AFM (Association Française contre les Myopathies, grant #10722 and #12325). GB and RBY are members of the European consortium "Euro-Laminopathies" supported by an EU-FP7 grant (#018690). GB, FL, RBY are supported by the Institut National de la Santé et de la Recherche Médicale, the Assistance Publique des Hôpitaux de Paris, the Centre National de la Recherche Scientifique and the Universités Paris V and Paris VI.

Author History

Rabah Ben Yaou, MD (2004-present)
Gisèle Bonne, PhD (2004-present)
France Leturcq, MD (2004-present)
Dominique Récan-Budiartha, MD; Hôpital Cochin (2004-2010)

Revision History

  • 25 November 2015 (me) Comprehensive update posted live
  • 17 January 2013 (me) Comprehensive update posted live
  • 24 August 2010 (cd) Revision: sequence analysis and prenatal testing for FHL1 mutations available clinically
  • 15 June 2010 (me) Comprehensive update posted live
  • 21 November 2007 (cd) Revision: LMNA deletion/duplication testing available clinically
  • 26 April 2007 (me) Comprehensive update posted live
  • 29 September 2004 (me) Review posted live
  • 27 January 2004 (gb) Original submission
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