Centronuclear myopathy
Encyclopedia
Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.
Symptoms of CNM include severe hypotonia
, hypoxia
-requiring breathing assistance, and scaphocephaly
. Among centronuclear myopathies, the X-linked myotubular myopathy form typically presents at birth, and is thus considered a congenital myopathy. However, some centronuclear myopathies may present later in life.
Literally, a myopathy is a disease
of the muscle tissue itself. Myo derives from the word muscle and pathos means disease. There are literally dozens of different myopathies, and myopathies are not the only conditions that can cause muscle weakness. Other diseases can cause weakness such as medical conditions affecting sites outside of the muscle itself, including problems in the brain (such as stroke
, cerebral palsy
, multiple sclerosis
), or problems in the spinal cord and/or nerve (such as polio and spinal muscular atrophy
).
, which upon muscle biopsy
, showed that the nuclei of the muscle cells were located in the center of the muscle cells, instead of their normal location of the periphery.
The nuclear appearance reminded him of the nucleus-in-the-center appearance during the “myotubular” stage of embryo
nic development. Thus, he coined the term "myotubular myopathy". Spiro speculated that the embryonic muscle development he had seen in the boy was due to growth arrest during the myotubular phase, causing the myopathy.
More than three decades later, it is not fully understood whether this theory regarding halted (or delayed) embryonic muscle development is correct. Some research suggests that this theory may be acceptable for infant-onset myotubular myopathy (mutations at the MTM1 gene on the X chromosome
), but may not be acceptable for the autosomal forms of centronuclear myopathy. While, other research suggests that the growth arrest mechanism may be responsible for all forms of MTM and CNM.
Regardless of whether the myopathy is caused by arrest at the "myotubular" stage, for historical reasons the name myotubular myopathy persists and is widely accepted.
As a reference to the term myotubular myopathy (MTM), when a genetic
abnormality on the X chromosome was determined to be involved in a substantial percentage of individuals with the myotubular/centronuclear appearance on muscle biopsy
, researchers named the gene segment MTM1. Similarly, the protein typically produced by that gene, is called "myotubularin
".
will have a mutation in MTM1 identifiable by genetic sequence analysis.
Many patients with myotubular myopathy die in infancy prior to receiving a formal diagnosis
. When possible, muscle biopsy and genetic testing may still be helpful even after a neonatal death, since the diagnostic information can assist with family planning
and genetic counseling
, as well as aiding in the accurate diagnosis of any relatives who might also have the same genetic abnormality.
at site Xq28. MTM1 codes for the myotubularin
protein, a highly conserved lipid phosphatase
involved in cellular transport, trafficking and signalling. Approximately 80% of males with myotubular myopathy diagnosed by muscle biopsy have mutations in MTM1, and about 7% of these mutations are genetic deletion
s.
Centronuclear myopathies where the genetic abnormality is NOT sex-linked (e.g., not located on the X chromosome) are considered autosomal. Autosomal abnormalities can either be dominant or recessive, and are often referred to as AD for "autosomal dominant" or AR for "autosomal recessive").
Many researchers use the term "myotubular myopathy" (MTM) only for cases when the genetic test has come back positive for abnormalities (genetic mutations) at the MTM1 gene on the X chromosome. Cases with a centronuclear (nucleus in the center) appearance on muscle biopsy but a normal genetic test for MTM1 would be referred to as centronuclear myopathy until such time as a specific genetic site is identified to give a more detailed sub-classification.
The possible combinations of inheritance of myotubular myopathy are as follows:
Sporadic cases have also been reported where there is no previous family history (these cases are presumably due to a new mutation that was not present in either parent).
, severe weakness, delayed developmental milestones (particularly gross motor milestones such as head control, crawling, and walking) and pulmonary complications (presumably due to weakness of the muscles responsible for respiration). While some patients with centronuclear myopathies remain ambulatory
throughout their adult life, others may never crawl or walk and may require wheelchair use for mobility. There is substantial variability in the degree of functional impairment among the various centronuclear myopathies.
Other observed features have been high arched palate, long digits, bell shaped chest and long face, it has to be added that myotubular myopathy only affects muscles and does not impact intelligence in any shape or form.
Although this condition only affects the voluntary muscles, several children have suffered from cardiac arrest, possibly due to the additional stress placed on the heart.
X-linked myotubular myopathy was traditionally a fatal condition of infancy, with life expectancy of usually less than two years. There appears to be substantial variability in the clinical severity for different genetic abnormalities at that same MTM1 gene. Further, published cases show significant differences in clinical severity among relatives with the same genetic abnormality at the MTM1 gene. Most truncating mutation
s of MTM1 cause a severe and early lethal phenotype
, while some missense mutation
s are associated with milder forms and prolonged survival (up to 54 years).
Centronuclear myopathies typically have a milder presentation and a better prognosis. Recently, researchers discovered mutations at the gene dynamin
2 (DNM2 on chromosome 19, at site 19p13.2), responsible for the autosomal dominant form of centronuclear myopathy. This condition is now known as dynamin 2 centronuclear myopathy (abbreviated DNM2-CNM). Research has indicated that patients with DNM2-CNM have a slowly progressive muscular weakness usually beginning in adolescence
or early adulthood, with an age range of 12 to 74 years.
material, the nuclear material is located predominantly in the center of the muscle cells, and is described as having any "myotubular" or "centronuclear" appearance. In terms of describing the muscle biopsy itself, "myotubular" or "centronuclear” are almost synonymous, and both terms point to the similar cellular-appearance among MTM and CNM. Thus, pathologists and treating physician
s use those terms almost interchangeably, although researcher
s and clinicians are increasingly distinguishing between those phrases.
In general, a clinical myopathy and a muscle biopsy showing a centronuclear (nucleus in the center of the muscle cell) appearance would indicate a centronuclear myopathy (CNM). The most commonly diagnosed CNM is myotubular myopathy (MTM). However, muscle biopsy analysis alone cannot reliably distinguish myotubular myopathy from other forms of centronuclear myopathies, and thus genetic testing
is required.
Diagnostic workup is often coordinated by a treating neurologist
. In the United States, care is often coordinated through clinics affiliated with the Muscular Dystrophy Association
.
and recording the response, and needle electromyography
, where a thin needle or pin-like electrode
is inserted into the muscle tissue to look for abnormal electrical activity.
Electrodiagnostic testing can help distinguish myopathies from neuropathies, which can help determine the course of further work-up. Most of the electrodiagnostic abnormalities seen in myopathies are also seen in neuropathies (nerve disorders). Electrodiagnostic abnormalities common to myopathies and neuropathies include; abnormal spontaneous activity (e.g., fibrillations, positive sharp waves, etc.) on needle EMG and, small amplitudes of the motor responses compound muscle action potential, or CMAP during nerve conduction studies. Many neuropathies, however, cause abnormalities of sensory nerve studies, whereas myopathies involve only the muscle, with normal sensory nerves. The most important factor distinguishing a myopathy from a neuropathy on needle EMG is the careful analysis of the motor unit action potential
(MUAP) size, shape, and recruitment pattern.
There is substantial overlap between the electrodiagnostic findings the various types of myopathy. Thus, electrodiagnostic testing can help distinguish neuropathy from myopathy, but is not effective at distinguishing which specific myopathy is present, here muscle biopsy
and perhaps subsequent genetic testing
are required.
Medical management generally involves efforts to prevent pulmonary complications, since lung infection
s can be fatal in patients lacking the muscle strength necessary to clear secretions via coughing. Medical devices to assist with coughing help patients maintain clear airways, avoiding mucous
plugs and avoiding the need for tracheostomy tubes.
Monitoring for scoliosis
is also important, since weakness of the trunk muscles can lead to deviations in spinal alignment, with resultant compromise of respiratory function. Many patients with congenital myopathies may eventually require surgical treatment of scoliosis.
, children with congenital myopathies often receive therapy services through Early Intervention Programs (EIP, providing services from birth to 3 years old) administered by the state of residence. After the child is 3 years old, Special Education
services are provided under the federal Individuals with Disabilities Education Act
(IDEA, with myopathies being eligible when classified under conditions causing muscular weakness). IDEA is meant to protect the rights of every disabled student to receive a free and appropriate public education (FAPE) in the least restrictive environment
(ideally meaning integrated with able-bodied classmates).
Centronuclear myopathies involve pathology at the skeletal muscles, generally without brain involvement or cognitive deficits. Even so, the motor deficits (weakness and associated impairments) may impede in individual’s ability to access the education
al curriculum
(e.g., difficulties lifting or carrying books, difficulties grasping a writing instrument, endurance difficulties throughout the school day, etc.). Further, recurrent respiratory infections may result in missed school days.
Symptoms of CNM include severe hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
-requiring breathing assistance, and scaphocephaly
Scaphocephaly
Scaphocephaly , derived from the Greek skaphe , describes a specific variety of a long narrow head that resembles an inverted boat....
. Among centronuclear myopathies, the X-linked myotubular myopathy form typically presents at birth, and is thus considered a congenital myopathy. However, some centronuclear myopathies may present later in life.
Terminology
Although all forms of centronuclear myopathy are considered rare, the most commonly known form of CNM is Myotubular Myopathy (MTM). (The terms "centronuclear myopathy" and "myotubular myopathy" are sometimes equated.)Literally, a myopathy is a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of the muscle tissue itself. Myo derives from the word muscle and pathos means disease. There are literally dozens of different myopathies, and myopathies are not the only conditions that can cause muscle weakness. Other diseases can cause weakness such as medical conditions affecting sites outside of the muscle itself, including problems in the brain (such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
, multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
), or problems in the spinal cord and/or nerve (such as polio and spinal muscular atrophy
Spinal muscular atrophy
Spinal Muscular Atrophy is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscular atrophy and weakness. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness...
).
History
In 1966, Dr. Spiro (a New York City neurologist) published a medical report of a boy with myopathyMyopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
, which upon muscle biopsy
Muscle biopsy
In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A biopsy needle is usually inserted into a muscle, wherein a small amount of tissue remains. Alternatively, an "open biopsy" can be performed by obtaining the...
, showed that the nuclei of the muscle cells were located in the center of the muscle cells, instead of their normal location of the periphery.
The nuclear appearance reminded him of the nucleus-in-the-center appearance during the “myotubular” stage of embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic development. Thus, he coined the term "myotubular myopathy". Spiro speculated that the embryonic muscle development he had seen in the boy was due to growth arrest during the myotubular phase, causing the myopathy.
More than three decades later, it is not fully understood whether this theory regarding halted (or delayed) embryonic muscle development is correct. Some research suggests that this theory may be acceptable for infant-onset myotubular myopathy (mutations at the MTM1 gene on the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
), but may not be acceptable for the autosomal forms of centronuclear myopathy. While, other research suggests that the growth arrest mechanism may be responsible for all forms of MTM and CNM.
Regardless of whether the myopathy is caused by arrest at the "myotubular" stage, for historical reasons the name myotubular myopathy persists and is widely accepted.
As a reference to the term myotubular myopathy (MTM), when a genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
abnormality on the X chromosome was determined to be involved in a substantial percentage of individuals with the myotubular/centronuclear appearance on muscle biopsy
Muscle biopsy
In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A biopsy needle is usually inserted into a muscle, wherein a small amount of tissue remains. Alternatively, an "open biopsy" can be performed by obtaining the...
, researchers named the gene segment MTM1. Similarly, the protein typically produced by that gene, is called "myotubularin
Myotubularin
Myotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with . Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol -bi-phosphate...
".
Incidence
The overall incidence of myotubular myopathy is 1 in 50,000 male live births. The incidence of other centronuclear myopathies is unknown, but they are far less common than more well-known muscle disorders like Duchenne's muscular dystrophy. Approximately 80% of males with a diagnosis of myotubular myopathy by muscle biopsyMuscle biopsy
In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A biopsy needle is usually inserted into a muscle, wherein a small amount of tissue remains. Alternatively, an "open biopsy" can be performed by obtaining the...
will have a mutation in MTM1 identifiable by genetic sequence analysis.
Many patients with myotubular myopathy die in infancy prior to receiving a formal diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
. When possible, muscle biopsy and genetic testing may still be helpful even after a neonatal death, since the diagnostic information can assist with family planning
Family planning
Family planning is the planning of when to have children, and the use of birth control and other techniques to implement such plans. Other techniques commonly used include sexuality education, prevention and management of sexually transmitted infections, pre-conception counseling and...
and genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
, as well as aiding in the accurate diagnosis of any relatives who might also have the same genetic abnormality.
Genetic causes
The genetic abnormality associated with the X-linked form of myotubular myopathy (XLMTM) was first localized in 1990 to the X chromosomeX chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
at site Xq28. MTM1 codes for the myotubularin
Myotubularin
Myotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with . Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol -bi-phosphate...
protein, a highly conserved lipid phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
involved in cellular transport, trafficking and signalling. Approximately 80% of males with myotubular myopathy diagnosed by muscle biopsy have mutations in MTM1, and about 7% of these mutations are genetic deletion
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
s.
Centronuclear myopathies where the genetic abnormality is NOT sex-linked (e.g., not located on the X chromosome) are considered autosomal. Autosomal abnormalities can either be dominant or recessive, and are often referred to as AD for "autosomal dominant" or AR for "autosomal recessive").
Many researchers use the term "myotubular myopathy" (MTM) only for cases when the genetic test has come back positive for abnormalities (genetic mutations) at the MTM1 gene on the X chromosome. Cases with a centronuclear (nucleus in the center) appearance on muscle biopsy but a normal genetic test for MTM1 would be referred to as centronuclear myopathy until such time as a specific genetic site is identified to give a more detailed sub-classification.
The possible combinations of inheritance of myotubular myopathy are as follows:
| Inheritance | OMIM | Gene(s) | Description |
|---|---|---|---|
| X-linked recessive | MTM1 (X-linked myotubular myopathy X-linked myotubular myopathy X-linked myotubular myopathy is a myopathy associated with myotubularin 1.Genetically inherited traits and conditions are often referred to based upon whether they are located on the "sex chromosomes" versus whether they are located on "autosomal" chromosomes... ) |
The X-linked form of MTM/CNM is the most commonly diagnosed type. Almost all cases of X-linked MTM occurs in males. | |
| Autosomal recessive | BIN1 BIN1 Myc box-dependent-interacting protein 1 is a protein that in humans is encoded by the BIN1 gene.-Interactions:BIN1 has been shown to interact with Phospholipase D1, SNX4 and PLD2.-Further reading:... |
A "recessive" abnormality will only cause disease if both copies of the gene are abnormal. | |
| Autosomal dominant | DNM2 DNM2 Dynamin-2 is a protein that in humans is encoded by the DNM2 gene.-Interactions:DNM2 has been shown to interact with SNX9, SHANK1 and SHANK2.-External Links:* -Further reading:... (MYF6 Myf6 Myf6, myogenic factor 6 , is a myogenic regulatory factor .- Function :... and MTMR14 MTMR14 Myotubularin related protein 14 also known as MTMR14 is a protein which in humans is encoded by the MTMR14 gene.- Function :Expression of Mtmr14 increased with myotubule formation and differentiation... less common) |
A "dominant" abnormality will exert its abnormal influence (e.g., causing a disease or medical condition) regardless of whether the other copy of the gene is normal or not. Within centronuclear myopathies, researchers have identified an autosomal dominant form at a gene called dynamin Dynamin Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface as well as at the... 2 (DNM2) on chromosome 19, and this particular condition is now referred to as dynamin 2 centronuclear myopathy (DNM2-CNM). |
Sporadic cases have also been reported where there is no previous family history (these cases are presumably due to a new mutation that was not present in either parent).
Clinical presentation
As with other myopathies, the clinical manifestations of MTM/CNM are most notably muscle weakness and associated disabilities. Congenital forms often present with neonatal low muscle toneMuscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
, severe weakness, delayed developmental milestones (particularly gross motor milestones such as head control, crawling, and walking) and pulmonary complications (presumably due to weakness of the muscles responsible for respiration). While some patients with centronuclear myopathies remain ambulatory
Ambulatory
The ambulatory is the covered passage around a cloister. The term is sometimes applied to the procession way around the east end of a cathedral or large church and behind the high altar....
throughout their adult life, others may never crawl or walk and may require wheelchair use for mobility. There is substantial variability in the degree of functional impairment among the various centronuclear myopathies.
Other observed features have been high arched palate, long digits, bell shaped chest and long face, it has to be added that myotubular myopathy only affects muscles and does not impact intelligence in any shape or form.
Although this condition only affects the voluntary muscles, several children have suffered from cardiac arrest, possibly due to the additional stress placed on the heart.
X-linked myotubular myopathy was traditionally a fatal condition of infancy, with life expectancy of usually less than two years. There appears to be substantial variability in the clinical severity for different genetic abnormalities at that same MTM1 gene. Further, published cases show significant differences in clinical severity among relatives with the same genetic abnormality at the MTM1 gene. Most truncating mutation
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
s of MTM1 cause a severe and early lethal phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
, while some missense mutation
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
s are associated with milder forms and prolonged survival (up to 54 years).
Centronuclear myopathies typically have a milder presentation and a better prognosis. Recently, researchers discovered mutations at the gene dynamin
Dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface as well as at the...
2 (DNM2 on chromosome 19, at site 19p13.2), responsible for the autosomal dominant form of centronuclear myopathy. This condition is now known as dynamin 2 centronuclear myopathy (abbreviated DNM2-CNM). Research has indicated that patients with DNM2-CNM have a slowly progressive muscular weakness usually beginning in adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
or early adulthood, with an age range of 12 to 74 years.
Pathology
On examination of muscle biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
material, the nuclear material is located predominantly in the center of the muscle cells, and is described as having any "myotubular" or "centronuclear" appearance. In terms of describing the muscle biopsy itself, "myotubular" or "centronuclear” are almost synonymous, and both terms point to the similar cellular-appearance among MTM and CNM. Thus, pathologists and treating physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s use those terms almost interchangeably, although researcher
Researcher
A researcher is somebody who performs research, the search for knowledge or in general any systematic investigation to establish facts. Researchers can work in academic, industrial, government, or private institutions.-Examples of research institutions:...
s and clinicians are increasingly distinguishing between those phrases.
In general, a clinical myopathy and a muscle biopsy showing a centronuclear (nucleus in the center of the muscle cell) appearance would indicate a centronuclear myopathy (CNM). The most commonly diagnosed CNM is myotubular myopathy (MTM). However, muscle biopsy analysis alone cannot reliably distinguish myotubular myopathy from other forms of centronuclear myopathies, and thus genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
is required.
Diagnostic workup is often coordinated by a treating neurologist
Neurologist
A neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
. In the United States, care is often coordinated through clinics affiliated with the Muscular Dystrophy Association
Muscular Dystrophy Association
The Muscular Dystrophy Association is an American organization which combats muscular dystrophy and diseases of the nervous system and muscular system in general by funding research, providing medical and community services, and educating health professionals and the general public...
.
Electrodiagnostic Testing
Electrodiagnostic testing (also called electrophysiologic) includes nerve conduction studies which involves stimulating a peripheral motor or sensory nerveSensory nerve
Sensory nerves are nerves that receive sensory stimuli, such as how something feels and if it is painful, smooth, rough, etc.They are made up of nerve fibers, called sensory fibers .Sensory neurons are neurons that are activated by sensory input Sensory nerves are nerves that receive sensory...
and recording the response, and needle electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
, where a thin needle or pin-like electrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...
is inserted into the muscle tissue to look for abnormal electrical activity.
Electrodiagnostic testing can help distinguish myopathies from neuropathies, which can help determine the course of further work-up. Most of the electrodiagnostic abnormalities seen in myopathies are also seen in neuropathies (nerve disorders). Electrodiagnostic abnormalities common to myopathies and neuropathies include; abnormal spontaneous activity (e.g., fibrillations, positive sharp waves, etc.) on needle EMG and, small amplitudes of the motor responses compound muscle action potential, or CMAP during nerve conduction studies. Many neuropathies, however, cause abnormalities of sensory nerve studies, whereas myopathies involve only the muscle, with normal sensory nerves. The most important factor distinguishing a myopathy from a neuropathy on needle EMG is the careful analysis of the motor unit action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
(MUAP) size, shape, and recruitment pattern.
There is substantial overlap between the electrodiagnostic findings the various types of myopathy. Thus, electrodiagnostic testing can help distinguish neuropathy from myopathy, but is not effective at distinguishing which specific myopathy is present, here muscle biopsy
Muscle biopsy
In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A biopsy needle is usually inserted into a muscle, wherein a small amount of tissue remains. Alternatively, an "open biopsy" can be performed by obtaining the...
and perhaps subsequent genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
are required.
Treatment
Currently there is no cure for myotubular or centronuclear myopathies. Treatment often focuses on trying to maximize functional abilities and minimize medical complications, and involvement by physicians specializing in Physical Medicine and Rehabilitation, and by physical therapists and occupational therapists.Medical management generally involves efforts to prevent pulmonary complications, since lung infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s can be fatal in patients lacking the muscle strength necessary to clear secretions via coughing. Medical devices to assist with coughing help patients maintain clear airways, avoiding mucous
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
plugs and avoiding the need for tracheostomy tubes.
Monitoring for scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
is also important, since weakness of the trunk muscles can lead to deviations in spinal alignment, with resultant compromise of respiratory function. Many patients with congenital myopathies may eventually require surgical treatment of scoliosis.
Advocacy
In the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, children with congenital myopathies often receive therapy services through Early Intervention Programs (EIP, providing services from birth to 3 years old) administered by the state of residence. After the child is 3 years old, Special Education
Special education
Special education is the education of students with special needs in a way that addresses the students' individual differences and needs. Ideally, this process involves the individually planned and systematically monitored arrangement of teaching procedures, adapted equipment and materials,...
services are provided under the federal Individuals with Disabilities Education Act
Individuals with Disabilities Education Act
The Individuals with Disabilities Education Act is a United States federal law that governs how states and public agencies provide early intervention, special education, and related services to children with disabilities...
(IDEA, with myopathies being eligible when classified under conditions causing muscular weakness). IDEA is meant to protect the rights of every disabled student to receive a free and appropriate public education (FAPE) in the least restrictive environment
Least Restrictive Environment
As part of the U.S. Individuals with Disabilities Education Act, the least restrictive environment is identified as one of the six principles that govern the education of students with disabilities and other special needs...
(ideally meaning integrated with able-bodied classmates).
Centronuclear myopathies involve pathology at the skeletal muscles, generally without brain involvement or cognitive deficits. Even so, the motor deficits (weakness and associated impairments) may impede in individual’s ability to access the education
Education
Education in its broadest, general sense is the means through which the aims and habits of a group of people lives on from one generation to the next. Generally, it occurs through any experience that has a formative effect on the way one thinks, feels, or acts...
al curriculum
Curriculum
See also Syllabus.In formal education, a curriculum is the set of courses, and their content, offered at a school or university. As an idea, curriculum stems from the Latin word for race course, referring to the course of deeds and experiences through which children grow to become mature adults...
(e.g., difficulties lifting or carrying books, difficulties grasping a writing instrument, endurance difficulties throughout the school day, etc.). Further, recurrent respiratory infections may result in missed school days.
External links
- GeneReviews/NCBI/NIH/UW entry on X-Linked Myotubular Myopathy or Centronuclear Myopathy
- MDA Hellas (Muscular Dystrophy Association's website)
- Myotubular Myopathy from the Muscular Dystrophy Association
- Myotubular Myopathy Resource Group
- The Information Point for Centronuclear and Myotubular Myopathy
- Myotubular Trust http://www.myotubulartrust.com