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Emery-Dreifuss Muscular Dystrophy

, PhD, , MD, and , MD.

Author Information
, PhD
Sorbonne Universités
UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617
Centre de Recherche en Myologie
Paris, France
, MD
AP-HP, Laboratoire de Biochimie & Génétique Moléculaire
Hôpital Cochin
Sorbonne Universités
UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617
Centre de Recherche en Myologie
Paris, France
, MD
Sorbonne Universités
UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617
Centre de Recherche en Myologie
Service des Bases de Données
Institut de Myologie
AP-HP, Groupe Hospitalier-Universitaire La Pitié-Salpêtrière
Centre de Référence de Maladies Neuromusculaires Paris-Est
Paris, France

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

Summary

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.

Diagnosis/testing.

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.

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 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 mutation. 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.

Diagnosis

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 multi-gene panel, and 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:
    • If clear X- linked inheritance, EMD should be analyzed first, followed by FHL1.
    • If clear autosomal dominant inheritance, LMNA should be analyzed first.
    • In absence of these clear inheritances, LMNA should be analyzied first, followed by EMD and then FHL1.
    • In affected females who are simplex cases (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 multi-gene panel that includes EMD, FHL1, LMNA and other genes of interest (see Differential Diagnosis) may also be considered. Note: The genes included and the sensitivity of multi-gene panels vary by laboratory and over time.

Genomic testing may be considered if serial single-gene testing (and/or use of a multi-gene panel) has not confirmed a diagnosis in an individual with features of EDMD. Such testing may include whole-exome sequencing (WES), whole-genome sequencing (WGS), and whole mitochondrial sequencing (WMitoSeq).

For issues to consider in interpretation of genomic test results, click 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 11
99% 10Unknown 12
Unknown 13NA
1.
2.

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

3.

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.

4.

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.

5.

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

6.

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.

7.

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].

8.

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].

9.

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].

10.

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].

11.

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].

12.

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.

13.

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, 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 [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].

Penetrance

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].

Prevalence

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
SMCHD1
FAT1
AD+++ (scapuloperoneal)Absence of joint contractures & cardiac disease
Other scapuloperoneal syndromes (neurogenic and myopathic types)DES
MYH7
TRPV4
181400
181405
181430
608358
255160
AD
AR
+++++ (MYH7, DES)Absence of joint contractures (MYH7, DES) & cardiac disease (TRPV4)
SYNE1-related disordersSYNE1612998
612999
AD+++++Unavailable pending description of additional cases
TMEM43-related myopathiesTMEM43614302AD++++ / –+ / –Unavailable pending description of clear phenotype
SUN1-related disordersSUN1607723
613569
AD++++Absence of cardiac disease
Rigid spine syndromeSEPN1602771AR+++++Absence of cardiac disease; early & severe respiratory failure
TTN-related myopathies
(see Salih Myopathy, Hereditary Myopathy w/Early Respiratory Failure, Udd Distal Myopathy)
TTNAD
AR
+++++++ / –Variably present cardiac disease; severe respiratory involvement; specific muscle pathology
LAMA2-related muscular dystrophyLAMA2AR++++++ / –Leukodystrophy
FKRP-related muscle diseases (see Limb-Girdle Muscular Dystrophy, Congenital Muscular Dystrophy)FKRPAR++++/ –+ / –Variably present cardiac disease; possible central nervous system involvement
Collagen type VI-related Bethlem myopathyCOL6A1
COL6A2
COL6A3
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
1.

Typical MOI; exceptions occur

2.

Management

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 medical 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].

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 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:

  • Molecular genetic testing if the LMNA, EMD, or FHL1 pathogenic variant(s) in the family are known;
  • Cardiac evaluation if the pathogenic variant(s) in the family are not known.

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 ClinicalTrials.gov 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

  • The father of an affected male will not have the disease nor will he be hemizygous for the EMD or FHL1 pathogenic variant; therefore, he does not require further evaluation/testing.
  • In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote (carrier). Note: If a woman has more than one affected son and no other affected relatives and if the EMD or FHL1 pathogenic variant cannot be detected in her leukocyte DNA, she has germline mosaicism. Germline mosaicism has been reported in XL-EDMD [Manilal et al 1998].
  • If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote or the affected male may have a de novo EMD or FHL1 pathogenic variant, in which case the mother is not a heterozygote. The frequency of de novo pathogenic variants is thought to be less than 1/3, as expected in lethal diseases, although no published data from large series are available [Wulff et al 1997, Yates & Wehnert 1999].
  • Female heterozygotes 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 Management, Evaluation of Relatives at Risk.)

Sibs of a proband

  • The risk to sibs depends on the genetic status of the mother.
  • If the mother of the proband has an EMD or FHL1 pathogenic variant, the chance of transmitting it in each pregnancy is 50%.
  • If the proband represents a simplex case (i.e., a single occurrence in a family) and if the EMD or FHL1 pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is low but greater than that of the general population because of the possibility of maternal germline mosaicism. Germline mosaicism has been reported in XL-EDMD [Manilal et al 1998].

Offspring of a proband

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

  • The parents of an affected individual are typically obligate heterozygotes (i.e., carriers of one LMNA pathogenic variant).
  • 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.)

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 or preimplantation genetic diagnosis for a pregnancy at increased risk for Emery-Dreifuss muscular dystrophy may be an option that a couple may wish to consider

Resources

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

  • National Library of Medicine Genetics Home Reference
  • Association Francaise contre les Myopathies (AFM)
    1 Rue de l'International
    BP59
    Evry cedex 91002
    France
    Phone: +33 01 69 47 28 28
    Email: dmc@afm.genethon.fr
  • European Neuromuscular Centre (ENMC)
    Lt Gen van Heutszlaan 6
    3743 JN Baarn
    Netherlands
    Phone: 31 35 5480481
    Fax: 31 35 5480499
    Email: enmc@enmc.org
  • Muscular Dystrophy Association - USA (MDA)
    222 South Riverside Plaza
    Suite 1500
    Chicago IL 60606
    Phone: 800-572-1717
    Email: mda@mdausa.org
  • Muscular Dystrophy Campaign
    61A Great Suffolk Street
    London SE1 0BU
    United Kingdom
    Phone: 0800 652 6352 (toll-free); 020 7803 4800
    Email: info@muscular-dystrophy.org

Molecular Genetics

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

Table A.

Emery-Dreifuss Muscular Dystrophy: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

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

150330LAMIN A/C; LMNA
181350EMERY-DREIFUSS MUSCULAR DYSTROPHY 2, AUTOSOMAL DOMINANT; EDMD2
300163FOUR-AND-A-HALF LIM DOMAINS 1; FHL1
300384EMERIN; EMD
300696MYOPATHY, X-LINKED, WITH POSTURAL MUSCLE ATROPHY; XMPMA
310300EMERY-DREIFUSS MUSCULAR DYSTROPHY 1, X-LINKED; EDMD1

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].

EMD

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

Benign allelic variants. Benign allelic variants have been identified.

Pathogenic allelic 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].

FHL1

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

Benign allelic variants. Benign allelic variants have been identified.

Pathogenic allelic 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 mutant protein in muscles of affected individuals. The out-of-frame insertions or deletions give rise to truncated mutant 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].

LMNA

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 allelic 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 Allelic Variants

DNA Nucleotide ChangeProtein Amino Acid ChangeReference Sequences
c.664C>Tp.His222Tyr 1NM_005572​.3
c.674G>Ap.Arg225Gln

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 (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

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 haploinsufficency with expression of only the normal allele (~50% of normal protein levels); the mutant 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.

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Suggested Reading

  1. 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]
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  3. 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.
  4. 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]
  5. 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]
  6. 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

Acknowledgments

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 to live Web site
  • 29 September 2004 (me) Review posted to live Web site
  • 27 January 2004 (gb) Original submission
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