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| {{Infobox medical condition (new) | | {{Short description|A congenital neuromuscular disorder}} |
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| '''Nemaline myopathy''' (also called '''rod myopathy''' or '''nemaline rod myopathy''') is a [[congenital]], [[hereditary]] neuromuscular disorder with many symptoms that can occur such as muscle weakness, [[hypoventilation]], swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births.<ref>{{Cite journal|last=Yuen|first=Michaela|last2=Sandaradura|first2=Sarah A.|last3=Dowling|first3=James J.|last4=Kostyukova|first4=Alla S.|last5=Moroz|first5=Natalia|last6=Quinlan|first6=Kate G.|last7=Lehtokari|first7=Vilma-Lotta|last8=Ravenscroft|first8=Gianina|last9=Todd|first9=Emily J.|date=2014-11-03|title=Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy|journal=The Journal of Clinical Investigation|volume=124|issue=11|pages=4693–4708|doi=10.1172/JCI75199|issn=0021-9738|pmc=4347224|pmid=25250574}}</ref> It is the most common non-dystrophic myopathy.<ref name="de Winter 383–392">{{Cite journal|last=de Winter|first=Josine Marieke|last2=Buck|first2=Danielle|last3=Hidalgo|first3=Carlos|last4=Jasper|first4=Jeffrey R.|last5=Malik|first5=Fady I.|last6=Clarke|first6=Nigel F.|last7=Stienen|first7=Ger J. M.|last8=Lawlor|first8=Michael W.|last9=Beggs|first9=Alan H.|date=2013-06-01|title=Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations|journal=Journal of Medical Genetics|volume=50|issue=6|pages=383–392|doi=10.1136/jmedgenet-2012-101470|issn=1468-6244|pmc=3865762|pmid=23572184}}</ref><ref>{{Cite journal|last=Ottenheijm|first=Coen A. C.|last2=Lawlor|first2=Michael W.|last3=Stienen|first3=Ger J. M.|last4=Granzier|first4=Henk|last5=Beggs|first5=Alan H.|date=2011-05-15|title=Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy|journal=Human Molecular Genetics|volume=20|issue=10|pages=2015–2025|doi=10.1093/hmg/ddr084|issn=1460-2083|pmc=3080611|pmid=21357678}}</ref>
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| "Myopathy" means muscle disease. Muscle fibers from a person with nemaline myopathy contains thread-like<ref>[http://ghr.nlm.nih.gov/condition/nemaline-myopathy nemaline myopathy]</ref> rods, sometimes called nemaline bodies.<ref>{{Cite web|url=http://rarediseases.org/rare-diseases/nemaline-myopathy/|title=Nemaline Myopathy - NORD (National Organization for Rare Disorders)|website=NORD (National Organization for Rare Disorders)|language=en-US|access-date=2016-04-25}}</ref> While the rods are diagnostic of the disorder, they are more likely a byproduct of the disease process rather than causing any dysfunction on their own. People with nemaline myopathy (NM) usually experience delayed motor development, or no motor development in severe cases, and weakness may occur in all of the skeletal muscles, such as muscles in the arms, legs, torso, neck flexors, throat, and face. The weakness tends to be more severe in the [[Anatomical terms of location|proximal muscles]] rather than the distal muscles. The ocular muscles are normally spared.
| | '''Nemaline myopathy''' is a [[congenital myopathy]] characterized by muscle weakness of varying severity, typically presenting at birth or in early childhood. It is one of the most common forms of congenital myopathy and is named for the thread-like or rod-like structures, called nemaline bodies, that are found in muscle fibers when viewed under a microscope. |
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| The disorder is often clinically categorized into groups with wide ranges of overlapping severity, from the most severe neonatal form which is incompatible with life, to a form so mild that it may not be diagnosed since the person appears to function at the lowest end of normal strength and breathing adequacy. [[Sporadic late onset nemaline myopathy]] (SLONM) is not a congenital disorder and is considered a different muscle disease from NM, which has its onset at birth or early childhood.<ref>{{Cite journal|last=Chahin|first=Nizar|last2=Selcen|first2=Duygu|last3=Engel|first3=Andrew G.|date=2005-10-25|title=Sporadic late onset nemaline myopathy|journal=Neurology|volume=65|issue=8|pages=1158–1164|doi=10.1212/01.wnl.0000180362.90078.dc|issn=1526-632X|pmid=16148261}}</ref> Respiratory problems are usually a primary concern for people with all forms of NM, and respiratory infections are quite common. NM shortens life expectancy, particularly in the more severe forms, but aggressive and proactive care allows most individuals to survive and even lead active lives.
| | ==Presentation== |
| | Nemaline myopathy presents with a range of symptoms that can vary significantly in severity. Common features include: |
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| Nemaline myopathy is one of the neuromuscular diseases covered by the [[Muscular Dystrophy Association]] in the United States.
| | * Generalized muscle weakness |
| | * Hypotonia (reduced muscle tone) |
| | * Delayed motor development |
| | * Facial muscle weakness, leading to a characteristic facial appearance |
| | * Respiratory difficulties due to weakness of the respiratory muscles |
| | * Feeding difficulties in infants |
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| == Signs and symptoms ==
| | The severity of symptoms can range from mild, where individuals lead relatively normal lives, to severe, where significant medical intervention is required. |
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| Signs vary from person to person. Young children and babies lack movement and have a difficult time eating and breathing. For young children not diagnosed immediately at birth, these are usually the first visible symptoms. One sign is a swollen face in disproportional areas. Other examples in newborns include swaying and a difficulty in moving. Other symptoms include feeble muscles in the neck and upper rib cage area. In adults, the most common symptom is respiratory problems.<ref name=":2" /> Other symptoms in adults could range from mild to severe speech impediments. It is common to be diagnosed with scoliosis in relations to nemaline myopathy.<ref name=":1">{{Cite web|url=https://www.mda.org/disease/inherited-and-endocrine-myopathies/types/nemaline-myopathy|title=Diseases - Inherited / Endocrine Myopathies - Type Of (Nemaline myopathy)|website=Muscular Dystrophy Association|access-date=2016-04-10|date=2015-12-18}}</ref>
| | ==Pathophysiology== |
| As babies that have NM develop and become of age when they should start walking, many take longer than average due to the lack of muscle, or just muscle fatigue.<ref name="Cap-Like" />
| | Nemaline myopathy is caused by mutations in several genes that are important for muscle function. These genes include: |
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| Since facial muscles are involved in NM takeover, elongated faces and a lower mandible are often observed in people with NM. People affected by NM usually will begin to feel muscle exhaustion between ages 20–50. Because NM only becomes worse, even with treatment, people who show early signs of NM only become weaker faster as opposed to a teenager who is just now showing symptoms, for example. [[Gastroesophageal reflux]], although not common, is associated with NM. Heart abnormalities can occur as a result of NM, but the likelihood of that happening are not high.<ref name=":2">{{Cite web|url=https://www.nlm.nih.gov/medlineplus/muscledisorders.html|title=Muscle Disorders: MedlinePlus|website=www.nlm.nih.gov|access-date=2016-04-10}}</ref>
| | * '''ACTA1''' - encoding skeletal muscle alpha-actin |
| | * '''NEB''' - encoding nebulin |
| | * '''TPM3''' - encoding alpha-tropomyosin |
| | * '''TPM2''' - encoding beta-tropomyosin |
| | * '''TNNT1''' - encoding slow skeletal muscle troponin T |
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| ===Mobility and orthopedics===
| | These genetic mutations lead to the formation of nemaline bodies within muscle fibers, which disrupt normal muscle function and lead to the clinical symptoms observed. |
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| Most children with mild NM eventually walk independently, although often at a later age than their peers. Some use [[wheelchairs]] or other devices, such as walkers or braces, to enhance their mobility. Individuals with severe NM generally have limited limb movement and use wheelchairs full-time.
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| Because of weakness in the trunk muscles, people with NM are prone to [[scoliosis]], which usually develops in childhood and worsens during puberty. Many individuals with NM undergo [[spinal fusion]] surgery to straighten and stabilize their backs. [[Osteoporosis]] is also common in NM.
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| Although patients early on often have mobility in their joints that is past the normal range, as they age, joint deformities and [[scoliosis]] usually occur.<ref name="Socialstyrelsen">{{cite web|last1=Ohlsson|first1=Monica|title=Nemaline Myopathy|url=http://www.socialstyrelsen.se/rarediseases/nemalinemyopathy#anchor_7m|website=Socialstyrelsen|publisher=The Swedish Information Centre for Rare Diseases}}</ref> If the person with nemaline myopathy keeps an eye on his or her joints early on, the problems with them can be detected when they begin and their progression can be delayed. Treatment of joint problems ranges from stretching exercises with physical therapy to surgical introduction of braces. The benefits of exercise in people with nemaline myopathy are still being studied, however, researchers have seen improvements in muscle function from low-intensity exercise. Vigorous exercise and the use of heavy weights should be avoided.
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| ===Respiratory involvement===
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| Attention to respiratory issues is critical to the health of all people with NM. Infants with severe NM frequently experience respiratory distress at or soon after birth. Many are [[ventilator|ventilated]] via [[tracheostomy]], and with proper breathing assistance they may attain good health. Though respiratory compromise may not be immediately apparent in people with intermediate or mild NM, it nearly always exists to some extent. As in many neuromuscular disorders, [[hypoventilation]] can begin insidiously, and it may cause serious health problems if not remedied by the use of [[Variable positive airway pressure|noninvasive mechanical devices]] to assist breathing, particularly at night.
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| ===Communication and eating===
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| Bulbar (throat) muscle weakness is a main feature of nemaline myopathy. Most individuals with severe NM are unable to swallow and receive their nutrition through [[feeding tube]]s. Most people with intermediate and mild NM take some or all of their nutrition orally. Bulbar muscle impairment may also lead to difficulty with communication. People with NM often have [[hypernasal speech]] as a result of poor closure of the velopharyngeal port (between the [[soft palate]] and the back of the throat). Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and [[Augmentative and alternative communication|augmentative communication]] devices. Individuals with NM are usually highly sociable and intelligent, with a great desire to communicate.
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| ===Physical characteristics and effects===
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| Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles.<ref name="Nemaline Myopathies" /> People with severe NM show obvious symptoms at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and [[hypotonia|hypotonic]]. Children born with NM often gain strength as they grow, though the effect of muscle weakness on body features may become more evident with time. Adults with NM typically have a very slender physique.<ref name="Nemaline Myopathies" />
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| ==Causes==
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| Nemaline Myopathy is caused by mutations in one of at least 11 different genes.<ref name="de Winter 383–392"/><ref>{{Cite journal|last=Sandaradura|first=Sarah A.|last2=North|first2=Kathryn N.|date=2015-08-26|title=LMOD3: the "missing link" in nemaline myopathy?|journal=Oncotarget|volume=6|issue=29|pages=26548–26549|issn=1949-2553|pmc=4694930|pmid=26337340|doi=10.18632/oncotarget.5267}}</ref> Nemaline myopathy is a clinically and genetically [[heterogeneous]] disorder and both [[autosomal dominant]] and [[autosomal recessive]] forms can occur. Diagnosis is made based upon clinical signs such as muscle weakness, absent or low deep tendon reflexes (hyporeflexia), and a high-arched palate, along with electron-dense aggregates, called nemaline rods, being observed at the microscopic level within muscle fibers. Genetic confirmation through identification of a known genetic mutation in the patient is also an important component of diagnosis.<ref>{{Cite journal|last=North|first=Kathryn N.|last2=Wang|first2=Ching H.|last3=Clarke|first3=Nigel|last4=Jungbluth|first4=Heinz|last5=Vainzof|first5=Mariz|last6=Dowling|first6=James J.|last7=Amburgey|first7=Kimberly|last8=Quijano-Roy|first8=Susana|last9=Beggs|first9=Alan H.|date=2014-02-01|title=Approach to the diagnosis of congenital myopathies|journal=Neuromuscular Disorders|volume=24|issue=2|pages=97–116|doi=10.1016/j.nmd.2013.11.003|issn=1873-2364|pmid=24456932|pmc=5257342}}</ref><ref>{{Cite journal|last=Romero|first=Norma B.|last2=Sandaradura|first2=Sarah A.|last3=Clarke|first3=Nigel F.|date=2013-10-01|title=Recent advances in nemaline myopathy|journal=Current Opinion in Neurology|volume=26|issue=5|pages=519–526|doi=10.1097/WCO.0b013e328364d681|issn=1473-6551|pmid=23995272}}</ref>
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| The two most common gene mutations causing nemaline myopathy are found on ''[[Nebulin|NEB]]'' or ''[[ACTA1]]''.<ref>{{Cite journal|last=Wallgren-Pettersson|first=Carina|last2=Sewry|first2=Caroline A.|last3=Nowak|first3=Kristen J.|last4=Laing|first4=Nigel G.|date=2011-12-01|title=Nemaline myopathies|journal=Seminars in Pediatric Neurology|volume=18|issue=4|pages=230–238|doi=10.1016/j.spen.2011.10.004|issn=1558-0776|pmid=22172418}}</ref> Mutations of the NEB gene usually result in symptoms present at birth or beginning in early childhood. This mutation results in about 50% of affected nemaline myopathy patients. The most common inheritance pathway for those with mutations in ''NEB'' is autosomal recessive in which each parent carries one mutated copy along with one normal functioning copy of the gene, and they pass the mutated copy to their offspring. In some cases, occasionally with ''ACTA1'' mutations, NM can be caused by an inheritance pattern of autosomal dominance. This mutation results in about 15 to 25 percent of the NM cases.<ref name="Laing 1267–1277">{{Cite journal|last=Laing|first=Nigel G.|last2=Dye|first2=Danielle E.|last3=Wallgren-Pettersson|first3=Carina|last4=Richard|first4=Gabriele|last5=Monnier|first5=Nicole|last6=Lillis|first6=Suzanne|last7=Winder|first7=Thomas L.|last8=Lochmüller|first8=Hanns|last9=Graziano|first9=Claudio|date=2009-09-01|title=Mutations and Polymorphisms of the Skeletal Muscle α-Actin Gene (ACTA1)|journal=Human Mutation|volume=30|issue=9|pages=1267–1277|doi=10.1002/humu.21059|issn=1059-7794|pmc=2784950|pmid=19562689}}</ref> One reason why this is lower is because mutations resulting in the "ACTA1" gene would usually not be passed down from parents, and thus this type of mutation must happen spontaneously in the egg or sperm.<ref name="Cap-Like" /> When the condition is heritable, each pregnancy with the same partners has the same risk of passing the mutated genes to offspring. New mutations (de novo) can also occur causing NM and de novo mutations have been most often found to occur in the ''ACTA1'' gene.<ref name="Laing 1267–1277"/>
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| MYPN is the last found gene related to NM The risk of all cases of nemaline myopathy is the same in males and females.<ref name="Cap-Like">{{cite journal|last1=Piteau|first1=SJ|last2=Rossiter|first2=JP|last3=Smith|first3=RG|last4=MacKenzie|first4=JJ|title=Congenital Myopathy With Cap-Like Structures and Nemaline Rods: Case Report and Literature Review|journal=Pediatric Neurology|volume=51|issue=2|pages=192–197|publisher=Elsevier|doi=10.1016/j.pediatrneurol.2014.04.002|pmid=25079567|year=2014}}</ref>
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| [[File:Biopsy nemaline myopathy gomori.jpg|300px|thumb|An example of muscle cells with rods. The rods have been stained red and are located on the inside of the plasma membrane.]]
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| {| class="wikitable sortable"
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| |+Summary of Molecular Genetic Testing Used in Nemaline Myopathy<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK1288/table/nem.T.summary_of_molecular_genetic_testi/?report=objectonly|title=Table 1. [Summary of Molecular Genetic Testing Used in Nemaline Myopathy]. - GeneReviews® - NCBI Bookshelf|last=North|first=Kathryn N.|last2=Ryan|first2=Monique M.|date=2015-06-11|language=en|access-date=2016-04-25}}</ref>
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| ! colspan="1" rowspan="1" |Gene 1
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| ! colspan="1" rowspan="1" |Proportion of Nemaline Myopathy Attributed to Mutation of This Gene
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| ! colspan="1" rowspan="1" |Test Method
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| |-
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| | colspan="1" rowspan="2" |''[[Nebulin|NEB]]''
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| | rowspan="2" |Up to 50%
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| |Sequence analysis
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| |-
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| |Deletion/duplication analysis & targeted analysis for pathogenic variants
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| | colspan="1" rowspan="2" |''[[ACTA1]]''
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| | colspan="1" rowspan="2" |15%-25%
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |Deletion/duplication analysis
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| |-
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| | colspan="1" rowspan="2" |''[[TPM3]]''
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| | colspan="1" rowspan="2" |2%-3%
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |Deletion/duplication analysis
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| |-
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| | colspan="1" rowspan="2" |''[[TPM2]]''
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| | colspan="1" rowspan="2" |<1%
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |Deletion/duplication analysis
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| | colspan="1" rowspan="2" |''[[TNNT1]]''
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| | colspan="1" rowspan="2" |Almost exclusively in Old Amish
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |Deletion/duplication analysis
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| | colspan="1" rowspan="1" |''[[Cofilin-2|CFL2]]''
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| | colspan="1" rowspan="1" |Rare
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |''KBTBD13''
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| | colspan="1" rowspan="1" |Unknown
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |''KLHL40''
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| | colspan="1" rowspan="1" |20%
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |''[[KBTBD10|KLHL41]]''
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| | colspan="1" rowspan="1" |Unknown
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| | colspan="1" rowspan="1" |Sequence analysis
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| | colspan="1" rowspan="1" |''[[LMOD3]]''
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| | colspan="1" rowspan="1" |Unknown
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| | colspan="1" rowspan="1" |Sequence analysis
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| |-
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| | colspan="1" rowspan="1" |Unknown
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| | colspan="1" rowspan="1" |NA
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| | colspan="1" rowspan="1" |NA
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| |}
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| The physical capabilities of a given person with NM do not correlate well either with [[genotype]] or with muscle pathology as observed in the biopsy.<ref>{{cite journal |vauthors=Ryan MM, Ilkovski B, Strickland CD, etal |title=Clinical course correlates poorly with muscle pathology in nemaline myopathy |journal=Neurology |volume=60 |issue=4 |pages=665–73 |date=February 2003 |pmid=12601110 |doi=10.1212/01.WNL.0000046585.81304.BC }}</ref><!-- Deleted image removed: [[Image:nemaline.jpg|frame|none|A stained view of the nemaline bodies (rods) that can be found in the muscle of an individual with nemaline myopathy. While these rods are diagnostic of nemaline myopathy, they are most likely a byproduct, rather than a cause, of the disorder.]] -->
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| == Mechanism ==
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| Muscle cells contract in complex mechanical and chemical processes. If any part of the process or structure is disrupted, dysfunction will likely result, as in the case of those with genetic variations. In those with nemaline myopathy, muscle contraction is adversely affected. At the electron microscopic level, rod-shaped components can often be seen in some of the muscle cells, and when seen, are diagnostic for the condition called nemaline rod myopathy. The presence of these rods is not itself causing muscle weakness; rather they appear as a result of something going wrong within the muscle fiber. There is no connection between the number of rods found in the muscle cells and the amount of weakness a person has. All of the different gene mutations leading to the condition called nemaline myopathy that have been found so far are in genes that encode different components of the sarcomere.<ref name="Nemaline Myopathies">{{cite journal|last1=Wallgren|first1=Petterson|last2=Sewry|first2=CA|last3=Nowak|first3=KJ|last4=Laing|first4=NG|title=Nemaline Myopathies|pmid=22172418|doi=10.1016/j.spen.2011.10.004|volume=18|issue=4|year=2011|journal=Semin Pediatr Neurol|pages=230–8}}</ref> In normal muscle cells, the various parts of the muscle fibers that make up the sarcomere are distributed evenly in a pattern for effective muscle contraction. Evidence suggests that some kinds of NM affect the arrangement of these muscle fibers, causing the muscles to be unable to contract as efficiently or effectively.
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| [[File:Normal Sarcomere.svg|thumb|This is a simple example of a healthy sarcomere.]]
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| [[File:Nemaline myopathy sarcomere.svg|thumb|Example of a sarcomere with nemaline rods.]]
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| Nemaline myopathy is usually genetic and shows traits in the affected individual from birth or an early age. However, there are some cases of symptoms of nemaline myopathy not showing up until adulthood. These cases are usually not genetic. Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the muscle cells.<ref name="Nemaline Myopathies"/> Respiratory muscles are often more affected than other skeletal muscle groups. Cardiac muscle is usually not affected in nemaline myopathy patients and the ocular muscles are usually spared.
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| The different genes whose mutations lead to the different kinds of nemaline myopathies affect the cells and the person’s body differently. The first kind of nemaline myopathy identified is due to the Slow α-Tropomyosin Gene [[TPM3]] and varies from case to case with its severity. In this kind of nemaline myopathy, affected people are weaker and more affected in their lower limbs than their upper limbs.<ref name="Nemaline Myopathies"/>
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| As stated above, the most common genetic form of NM is caused by a mutation in the nebulin gene, called Nebulin,<ref>{{Cite web|url=https://www.wikigenes.org/e/gene/e/4703.html|title=WikiGenes - Collaborative Publishing|website=WikiGenes - Collaborative Publishing|access-date=2016-04-10}}</ref><ref>{{Cite journal|last=Li|first=Frank|last2=Buck|first2=Danielle|last3=De Winter|first3=Josine|last4=Kolb|first4=Justin|last5=Meng|first5=Hui|last6=Birch|first6=Camille|last7=Slater|first7=Rebecca|last8=Escobar|first8=Yael Natelie|last9=Smith|first9=John E.|date=2015-09-15|title=Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy|journal=Human Molecular Genetics|volume=24|issue=18|pages=5219–5233|doi=10.1093/hmg/ddv243|issn=1460-2083|pmc=4550825|pmid=26123491}}</ref> and has a range of severity levels. All published cases up to this point where NM is thought to be caused by a mutation in the ''NEB'' gene have been autosomal recessive and are the most common cause of nemaline myopathy.<ref>Ottenheijm, Lawlor, Steiner, Granzier, Beggs. "Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy"</ref> Patients with this kind of NM are more affected in the muscles in their head, rather than their proximal muscles at the core of their body. Consequently, patients with this genetic mutation often cannot lift their heads and speak with a nasal voice. There have been cases that suggest this kind of NM may lead to patients having higher intellect.<ref name="Nemaline Myopathies"/>
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| A third kind of nemaline myopathy in the Skeletal Muscle [[ACTA1|α-Actin Gene]] ACTA1 is due to a recessive null mutation.<ref name="Nemaline Myopathies"/> These patients do not always show the typical nemaline bodies in their muscle cells. The only abnormality they show is an abnormal distribution of muscle fibers.
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| There are several other identified kinds of mutations that lead to Nemaline Myopathies. One affects slow skeletal muscles, one leads to the formation of both nemaline bodies and other abnormal, core-like, structures forming in the patient’s muscles.
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| ==Diagnosis== | | ==Diagnosis== |
| * [[Electromyography]] or (EMG). This procedure determines if nerve or muscle cells are damaged. Since a common symptom of Nemaline Myopathy is muscle weakness this allows doctors to determine where and why the weakness is occurring.<ref name=":2" />
| | Diagnosis of nemaline myopathy is based on clinical evaluation, family history, and a combination of the following tests: |
| * [[MRI]] of the Musculoskeletal System. MRI uses a magnetic field to take pictures of body structures and allows physicians to determine if a patient has a certain disease.<ref name=":2" />
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| * [[Needle biopsy]] A needle biopsy allows a physician to test specific cells in the body. These cells are sent to a laboratory to undergo testing and can further determine why muscle weakness throughout the body could be occurring. This testing can confirm that muscle cells contain rod like structures.<ref name=":2" />
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| == Treatment ==
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| At present, Nemaline myopathy does not have a cure. Nemaline myopathy is a very rare disease that only affects 1 out of 50,000 on average, although recent studies show that this number is even smaller. There are a number of treatments to minimize the symptoms of the disease. The treatments and procedures to help patients with nemaline myopathy vary depending on the severity of the disease. A possible accommodation could be the use of a stabilizer, such as a brace. Other means include moderate stretching and moderate exercise to help target muscles maintain maximum health.<ref name=":3">{{Cite web|url=http://rarediseases.org/rare-diseases/nemaline-myopathy/|title=Nemaline Myopathy - NORD (National Organization for Rare Disorders)|website=NORD (National Organization for Rare Disorders)|language=en-US|access-date=2016-04-10}}</ref>
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| As people with NM grow and develop throughout their lives, it is important for them to see a variety of health professionals regularly, including a [[neurologist]], [[physical therapist]], and others, such as [[speech therapist]]s and [[psychologists]], to help both the patient and family adjust to everyday life.<ref name="Socialstyrelsen" />
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| == Outcome ==
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| Although there is no cure for NM, it is possible, and common for many people live healthy active lives even with moderate to severe cases.<ref name="Diseases-Inherited/Endocrine Myopathies">{{cite web|title=Diseases-Inherited/Endocrine Myopathies|url=https://www.mda.org/disease/inherited-and-endocrine-myopathies/types/nemaline-myopathy|publisher=Muscular Dystrophy Association|accessdate=27 April 2016|date=2015-12-18}}</ref> Research continues to seek ways to ameliorate debilitating symptoms and lengthen the life-span in quality ways for those affected. Some people have seen mild improvements in secretion handling, energy level, and physical functioning with supplemental L-tyrosine, an amino acid that is available through health centers.<ref>{{Cite journal|last=Ryan|first=Monique M.|last2=Sy|first2=Catherine|last3=Rudge|first3=Sian|last4=Ellaway|first4=Carolyn|last5=Ketteridge|first5=David|last6=Roddick|first6=Laurence G.|last7=Iannaccone|first7=Susan T.|last8=Kornberg|first8=Andrew J.|last9=North|first9=Kathryn N.|date=2008-06-01|title=Dietary L-tyrosine supplementation in nemaline myopathy|journal=Journal of Child Neurology|volume=23|issue=6|pages=609–613|doi=10.1177/0883073807309794|issn=0883-0738|pmid=18079309}}</ref> Some symptoms may worsen as the patient ages. Muscle loss increases with age naturally, but it is even more significant with nemaline myopathy.<ref>{{Cite web|url=http://www.socialstyrelsen.se/rarediseases/nemalinemyopathy#anchor_7m|title=Nemaline myopathy|website=www.socialstyrelsen.se|access-date=2016-04-10}}</ref>
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| == Current research ==
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| New research resources have become available for the NM community, such as the CMDIR (registry) and the CMD-TR (biorepository). These two resources connect families and individuals interested in participating in research with the scientists that aim to treat or cure NM. Some research on NM seeks to better understand the molecular effects the gene mutations have on muscle cells and the rest of the body<ref name="Genetics Home Reference">{{cite web|title=Nemaline Myopathy|url=https://ghr.nlm.nih.gov/condition/nemaline-myopathy|website=Genetics Home Reference|publisher=U.S. National Library of Medicine}}</ref> and to observe any connections NM may have to other diseases and health complications.
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| ==History ==
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| "Rod myopathy" was first identified by [[Douglas Reye]], an Australian physician, in 1958.<ref name="Westmead Children's Hospital - 09Aug2005 - Congenital myopathies and muscular dystrophies team">{{cite web|url=http://www.chw.edu.au/research/groups/neurogenetics/01_congenital.htm|title=Congenital myopathies and muscular dystrophies team|date=9 August 2005|publisher=[[Royal Alexandra Hospital for Children|Westmead Children's Hospital]]|accessdate=13 February 2012}}</ref> However, Reye's results were never published because another doctor dismissed his finding of rods in the muscle tissue as an artifact of the biopsy. Forty years later, Reye's "rod myopathy" patient was confirmed to have nemaline myopathy. Another group of Australian researchers has since published an article recognizing Reye for his work.<ref name="pmid10838259">{{cite journal |vauthors=Schnell C, Kan A, North KN |title='An artefact gone awry': identification of the first case of nemaline myopathy by Dr R.D.K. Reye |journal=Neuromuscul. Disord. |volume=10 |issue=4–5 |pages=307–12 |date=June 2000 |pmid=10838259 |doi= 10.1016/S0960-8966(99)00123-6}}</ref>
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| "Nemaline myopathy" was first named in a published paper in 1963 by North American researchers [[P.E. Cohen]] and G. M. Shy. Shy and his team discovered rod- like structures in [[muscle fibers]] of patients with [[muscle weakness]] by performing muscle biopsies on multiple patients.<ref name=":3" /> Laboratories performing research on NM are located around the world, notably in the United States, Canada, England, Finland, and Australia.
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| ==Society==
| | * [[Muscle biopsy]] - revealing the presence of nemaline bodies |
| | * [[Genetic testing]] - identifying mutations in the associated genes |
| | * [[Electromyography]] (EMG) - assessing muscle electrical activity |
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| The NM community has a number of resources to welcome affected individuals and their families, such as the [https://www.scribd.com/document/318353570/Nemaline-Myopathy-Welcome-Flyer-Spring2018 Nemaline Myopathy Welcome Flyer]. In 1999, the first website on nemaline myopathy was launched, and in October 2004, the first Nemaline Myopathy Convention was held in Toronto, Canada. Many more conferences and social events have been held since, and all events organized since 2008 have been co-sponsored by A Foundation Building Strength for Nemaline Myopathy (AFBS),<ref>{{Cite web|url=http://buildingstrength.org/research/|title=A Foundation Building Strength for Nemaline Myopathy Research|date=|website=|publisher=|access-date=}}</ref> the only foundation focused on supporting treatment development and social events for the NM community. In March 2006, Niki Shisler released a book, ''Fragile'', in which she recounted her experiences surrounding the birth of twin sons with severe NM. In 2014, a team of experts collaborated with affected individuals and families caring for someone with a congenital myopathy to develop the first guidebook on managing life with a congenital myopathy, like NM, found here [https://www.mcw.edu/Congenital-Muscle-Disease-CMD-Tissue-Repository/For-Patients-Families.htm The Care of Congenital Myopathy: A Guide for Families].
| | ==Management== |
| | There is currently no cure for nemaline myopathy, and treatment is primarily supportive. Management strategies include: |
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| ==References==
| | * Physical therapy to improve muscle strength and function |
| {{Reflist}}
| | * Respiratory support for individuals with breathing difficulties |
| | * Nutritional support for those with feeding difficulties |
| | * Orthopedic interventions for skeletal deformities |
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| == External links == | | ==Prognosis== |
| {{Medical resources
| | The prognosis for individuals with nemaline myopathy varies widely depending on the severity of the condition. Some individuals experience only mild symptoms and have a normal lifespan, while others with severe forms may have significant disability and reduced life expectancy. |
| | DiseasesDB = 31991
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| | ICD10 = {{ICD10|G|71|2|g|70}}
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| | ICD9 = {{ICD9|359.0}}
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| | OMIM = 161800
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| | OMIM_mult = {{OMIM2|256030}} {{OMIM2|605355}} {{OMIM2|609284}}
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| | eMedicineSubj = neuro
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| | eMedicineTopic = 76
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| | eMedicine_mult = {{eMedicine2|neuro|230}}
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| | GeneReviewsNBK = NBK1288
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| | GeneReviewsName = Nemaline myopathy
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| | Orphanet = 607
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| }}
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| *[https://www.ncbi.nlm.nih.gov/books/NBK1288/ GeneReview/NCBI/NIH/UW entry on Nemaline Myo\] | | ==Related pages== |
| {{Muscular Dystrophy}}
| | * [[Congenital myopathy]] |
| {{Diseases of myoneural junction and muscle}}
| | * [[Muscle biopsy]] |
| {{Cytoskeletal defects}}
| | * [[Genetic testing]] |
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| [[Category:Myoneural junction and neuromuscular diseases]] | | [[Category:Congenital disorders]] |
| [[Category:Autosomal recessive disorders]] | | [[Category:Neuromuscular disorders]] |
| [[Category:Rare diseases]] | | [[Category:Rare diseases]] |
A congenital neuromuscular disorder
Nemaline myopathy is a congenital myopathy characterized by muscle weakness of varying severity, typically presenting at birth or in early childhood. It is one of the most common forms of congenital myopathy and is named for the thread-like or rod-like structures, called nemaline bodies, that are found in muscle fibers when viewed under a microscope.
Presentation
Nemaline myopathy presents with a range of symptoms that can vary significantly in severity. Common features include:
- Generalized muscle weakness
- Hypotonia (reduced muscle tone)
- Delayed motor development
- Facial muscle weakness, leading to a characteristic facial appearance
- Respiratory difficulties due to weakness of the respiratory muscles
- Feeding difficulties in infants
The severity of symptoms can range from mild, where individuals lead relatively normal lives, to severe, where significant medical intervention is required.
Pathophysiology
Nemaline myopathy is caused by mutations in several genes that are important for muscle function. These genes include:
- ACTA1 - encoding skeletal muscle alpha-actin
- NEB - encoding nebulin
- TPM3 - encoding alpha-tropomyosin
- TPM2 - encoding beta-tropomyosin
- TNNT1 - encoding slow skeletal muscle troponin T
These genetic mutations lead to the formation of nemaline bodies within muscle fibers, which disrupt normal muscle function and lead to the clinical symptoms observed.
Diagnosis
Diagnosis of nemaline myopathy is based on clinical evaluation, family history, and a combination of the following tests:
Management
There is currently no cure for nemaline myopathy, and treatment is primarily supportive. Management strategies include:
- Physical therapy to improve muscle strength and function
- Respiratory support for individuals with breathing difficulties
- Nutritional support for those with feeding difficulties
- Orthopedic interventions for skeletal deformities
Prognosis
The prognosis for individuals with nemaline myopathy varies widely depending on the severity of the condition. Some individuals experience only mild symptoms and have a normal lifespan, while others with severe forms may have significant disability and reduced life expectancy.
Related pages
