HOME

TheInfoList



OR:

Emery–Dreifuss muscular dystrophy (EDMD) is a type of
muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...
, a group of heritable diseases that cause progressive impairment of muscles. EDMD affects muscles used for movement (
skeletal muscles Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
), causing atrophy, weakness, and contractures. It almost always affects the heart, causing abnormal rhythms, heart failure, or sudden cardiac death. It is rare, affecting 0.39 per 100,000 (1 per 250,000) people. It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.


Classification

Emery–Dreifuss muscular dystrophy can be sub-classified by pattern of inheritance:
X-linked Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...
,
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
, and
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
.update 2015 * Autosomal dominant: heart problems with weakness (and wasting) of skeletal muscles and
Achilles tendon The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcane ...
contractures. * X-linked: result of the ''EMD'' gene mutation, characterized by cardiac involvement. * Autosomal recessive: characterized by cardiac issues, such as
arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
.


Signs and symptoms

The classic triad of EDMD consists of early contractures, muscle weakness, and heart involvement, typically manifesting in adolescence. Contractures often manifest before weakness, and they can be more disabling. They tend to fix the elbow into flexion and ankle into plantarflexion via
Achilles tendon The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcane ...
shortening. The
spine Spine or spinal may refer to: Science Biology * Spinal column, also known as the backbone * Dendritic spine, a small membranous protrusion from a neuron's dendrite * Thorns, spines, and prickles, needle-like structures in plants * Spine (zoology), ...
is also affected, with limited neck
flexion Motion, the process of movement, is described using specific anatomical terminology, anatomical terms. Motion includes movement of Organ (anatomy), organs, joints, Limb (anatomy), limbs, and specific sections of the body. The terminology used de ...
initially, and eventually the entire spine can become fixed into extension, referred to as a rigid spine. Elbow and neck contractures seldom occur in other diseases. Eventually, orthopedics (walker, cane) may be needed. The weakness is slowly progressive and preferentially involves the muscles that overlie the
humerus The humerus (; : humeri) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius (bone), radius and ulna, and consists of three sections. The humeral upper extrem ...
bone (
biceps The biceps or biceps brachii (, "two-headed muscle of the arm") is a large muscle that lies on the front of the upper arm between the shoulder and the elbow. Both heads of the muscle arise on the scapula and join to form a single muscle bel ...
and
triceps The triceps, or triceps brachii (Latin for "three-headed muscle of the arm"), is a large muscle on the ventral, back of the upper limb of many vertebrates. It consists of three parts: the medial, lateral, and long head. All three heads cross the ...
muscles) and those situated on the outside of the lower leg ( peroneal). Later, the muscles that position the
scapula The scapula (: scapulae or scapulas), also known as the shoulder blade, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, the scapulae are paired, with each scapula on either side ...
can be weakened, completing a pattern that is termed 'scapulohumeroperoneal'. Weakness of the scapular fixators can cause a
winged scapula A winged scapula (scapula alata) is a skeletal medical condition in which the shoulder blade protrudes from a person's back in an abnormal position. In rare conditions it has the potential to lead to limited functional activity in the upper ex ...
, which can impair the ability to lift the arms over the head and can be painful. Weakness of the peroneal muscles can result in toe walking, which can present in the first decade of life. Facial, hand, and thigh muscles can be affected, although less often. Calf
hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Although hypertro ...
can occur. Involvement of the heart occurs in almost all cases, presenting as syncope in the second or third decades, or as
sudden cardiac death Cardiac arrest (also known as sudden cardiac arrest ''SCA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly circulate around the body and the blood flow to the brain and other org ...
. A multitude of cardiac arrhythmias can result, requiring a pacemaker often by age 30 years. Reported arrhythmias include
bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...
,
atrial fibrillation Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...
/ flutter, atrioventricular conduction defect, and atrial paralysis. Later in the disease,
cardiomyopathy Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
can occur. Sometimes, cardiac involvement is the predominant manifestation of EDMD, with minimal involvement of the
skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
s.


EDMD1

Skeletal muscle involvement usually occurs before cardiac involvement. Of female carriers, 10-20% have abnormal heart rhythm or conduction, with increased risk of
sudden cardiac death Cardiac arrest (also known as sudden cardiac arrest ''SCA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly circulate around the body and the blood flow to the brain and other org ...
.


EDMD2

The disease course of EDMD 2 is more severe than EDMD1. Compared to EDMD1, cardiac symptoms are more likely to be the initial manifestation. EDMD2 can result in a much broader spectrum of disease, and the severity of muscle weakness is less predictable. However, muscle weakness typically is slowly progressive in first three decades, with an increased rate of progression thereafter.


Genetics

Mutations in one of several genes cause the various types of Emery–Dreifuss muscular dystrophy. Mutation of the '' EMD'' or ''
LMNA Prelamin-A/C, or lamin A/C is a protein that in humans is encoded by the ''LMNA'' gene. Lamin A/C belongs to the lamin family of proteins. Function In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, r ...
'' gene is the cause in 40% of cases. Each gene implicated in EDMD provides instructions for making a protein that is associated with the
nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membran ...
, which surrounds the nucleus of a cell. The
nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membran ...
regulates the movement of molecules into and out of the nucleus, and researchers believe it may play a role in regulating the activity of certain genes. Mutations of the genes '' SUN1'' and '' SUN2'' have each been shown to cause EDMD in single cases. '' TTN'' has also been associated with EDMD phenotype. File:Protein LMNA PDB 1ifr.png, Protein LMNA File:Protein EMD PDB 1jei.png, Protein EMD File:Protein FHL1 PDB 1x63.png, Protein FHL1


Pathophysiology

Genetic mutations causing EDMD affect proteins comprising the
nuclear membrane The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer polar membrane, membranes that in eukaryotic cells surround the Cell nucleus, nucleus, which encloses the genome, genetic material. The nuclear envelope con ...
. Possibly, in all EDMD subtypes, there is impaired protein importation into the nucleus. Another possibility is that in all subtypes, there is a loss of nuclear structural integrity.


Diagnosis

A positive genetic test in a person with the signs and symptoms of EDMD provides a definitive diagnosis.
Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
can involve single- gene testing or genomic testing. Auxiliary testing can include the following:


Differential diagnosis

Contractures manifest early in the disease course. Other diseases that have early or congenital contractures are diseases involving
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
mutations, including Ullrich congenital muscular dystrophy and Bethlem myopathy. SELENON-related
myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...
and arthrogryposis multiplex congenita also cause congenital contractures. Weakness initially affects the humeral and peroneal muscles, progressing to involve the
scapula The scapula (: scapulae or scapulas), also known as the shoulder blade, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, the scapulae are paired, with each scapula on either side ...
r and pelvic muscles. Facioscapulohumeral muscular dystrophy has a similar muscle involvement pattern.


Management

Following diagnosis, the extent of the disease should be established regarding the heart, the lungs, and the muscles/bones (
musculoskeletal The human musculoskeletal system (also known as the human locomotor system, and previously the activity system) is an organ system that gives humans the ability to move using their muscular and skeletal systems. The musculoskeletal system provid ...
). Metabolic functions should also be assessed, as
lipodystrophy Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissu ...
can co-occur with EDMD, by measuring levels of sugar,
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
, and
triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...
s in the blood. Tests useful for heart evaluation include
electrocardiography Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity through repeated cardiac cycles. It is an electrogram of the heart which is a graph of voltage versus time of t ...
(EKG),
echocardiography Echocardiography, also known as cardiac ultrasound, is the use of ultrasound to examine the heart. It is a type of medical imaging, using standard ultrasound or Doppler ultrasound. The visual image formed using this technique is called an ec ...
(echo), cardiac MRI, and electrophysiology studies. Musculoskeletal function can be assessed by a
physical therapist Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease prevention ...
or orthopedist. Regardless of the extent of the disease, cardiac and respiratory complications should be monitored. EKG, holter, and echo are recommended yearly, and additional tests can be indicated depending on heart involvement. Pulmonary function tests (PFTs) are recommended every 2–3 years, or yearly in those with respiratory involvement. Although the root cause of EDMD is not currently treatable, its manifestations and complications can be treated. Heart involvement can be addressed with medications ( antiarrhythmics, beta-blockers, and
ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as ...
), pacemakers, defibrillators, and sometimes heart transplantation. Affecting breathing can be addressed with physical therapy and, later in the disease, mechanical ventilation.
Contracture In pathology, a contracture is a shortening of muscles, tendons, skin, and nearby soft tissues that causes the joints to shorten and become very stiff, preventing normal movement. A contracture is usually permanent, but less commonly can be temp ...
s and
scoliosis Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...
can be addressed with
orthopedic surgery Orthopedic surgery or orthopedics ( alternative spelling orthopaedics) is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...
. Mobility can be improved with physical therapy, occupational therapy, and mechanical aids (canes, orthoses, wheelchairs).


Epidemiology

It is rare, affecting 0.39 per 100,000 (1 per 250,000) people.


See also

*
Laminopathies Laminopathies ('' lamino-'' + '' -pathy'') are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. Since the first reports of laminopathies in the late 1990s, increased research efforts have sta ...
* Noncompaction cardiomyopathy


References


Further reading

* *


External links

{{DEFAULTSORT:Emery-Dreifuss muscular dystrophy Muscular dystrophy