Nemaline myopathy
Encyclopedia
Nemaline myopathy is a congenital, hereditary neuromuscular disorder that causes muscle weakness, generally nonprogressive, of varying severity.
"Myopathy" means "muscle disease," and a biopsy
of muscle from a person with nemaline myopathy shows abnormal thread-like rods, called nemaline bodies, in the muscle cells. People with nemaline myopathy (or NM) usually experience delayed motor development and weakness in the arm, leg, trunk, throat, and face muscles.
The disorder is often clinically categorized into several groups, including mild (typical), intermediate, severe, and adult-onset; however, these distinctions are somewhat ambiguous, as the categories frequently overlap. Respiratory problems are a primary concern for people with all forms of NM, and though in some severe cases they may threaten life expectancy, aggressive and proactive care allows most individuals to survive and lead active lives.
Nemaline myopathy is one of forty neuromuscular diseases covered by the Muscular Dystrophy Association
.
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.
"Nemaline myopathy" was first named in a published paper in 1963 by North American researchers Cohen and Shy. Today, laboratories performing research on NM are located in the United States (Boston), Finland, and Australia.
. 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.
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.
can begin insidiously, and it may cause serious health problems if not remedied by the use of noninvasive mechanical devices to assist breathing, particularly at night.
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 communication
devices. Individuals with NM are usually highly sociable and intelligent, with a great desire to communicate.
"Myopathy" means "muscle disease," and a biopsy
Biopsy
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...
of muscle from a person with nemaline myopathy shows abnormal thread-like rods, called nemaline bodies, in the muscle cells. People with nemaline myopathy (or NM) usually experience delayed motor development and weakness in the arm, leg, trunk, throat, and face muscles.
The disorder is often clinically categorized into several groups, including mild (typical), intermediate, severe, and adult-onset; however, these distinctions are somewhat ambiguous, as the categories frequently overlap. Respiratory problems are a primary concern for people with all forms of NM, and though in some severe cases they may threaten life expectancy, aggressive and proactive care allows most individuals to survive and lead active lives.
Nemaline myopathy is one of forty neuromuscular diseases covered by 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...
.
Genetic qualities
Nemaline myopathy is a clinically and genetically heterogeneous disorder. Both autosomal dominant and autosomal recessive forms occur. Genetic mutations found to be responsible for the disorder include| Gene | Type | OMIM | Locus | Notes |
|---|---|---|---|---|
| TPM3 | NEM1 | |||
| NEB Nebulin Nebulin is an actin-binding protein which is localized to the I-band of the sarcomeres in skeletal muscle. It is a very large protein and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler"... |
NEM2 | 2q22 | ||
| ACTA1 ACTA1 Actin, alpha skeletal muscle is a protein that in humans is encoded by the ACTA1 gene.-Skeletal actin gene expression:Skeletal alpha actin expression is induced by stimuli and conditions known to cause muscle formation. Such conditions result in fusion of committed cells into myotubes, to form... |
NEM3 | 1q22-q23, 9p13.2-p13.1, 1q42.1 | ||
| TPM2 TPM2 Tropomyosin beta chain is a protein that in humans is encoded by the TPM2 gene.-Interactions:TPM2 has been shown to interact with RRAD, PDLIM7 and TPM1.-External links:* -Further reading:... |
NEM4 | |||
| TNNT1 TNNT1 Troponin T, slow skeletal muscle is a protein that in humans is encoded by the TNNT1 gene.-External links:* -Further reading:... |
NEM5 | 19q13.4 | Also known as Amish nemaline myopathy |
The physical capabilities of a given person with NM do not correlate well either with genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
or with muscle pathology as observed in the biopsy.
History and early identification
"Rod myopathy" was first identified by Dr. Douglas Reye, an Australian physician, in 1958. 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."Nemaline myopathy" was first named in a published paper in 1963 by North American researchers Cohen and Shy. Today, laboratories performing research on NM are located in the United States (Boston), Finland, and Australia.
Physical characteristics and effects
Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles. People with severe NM are usually obviously affected at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and hypotonicHypotonia
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...
. 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.
Mobility and orthopedics
Most children with mild NM eventually walk independently, although often at a later age than their peers. Some use wheelchairs or other devices to enhance their mobility. Individuals with severe NM generally have limited limb movement and use wheelchairs fulltime.Because of weakness in the trunk muscles, people with NM are prone to 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...
, which usually develops in childhood and worsens during puberty. Many individuals with NM undergo spinal fusion
Spinal fusion
Spinal fusion, also known as spondylodesis or spondylosyndesis, is a surgical technique used to join two or more vertebrae. Supplementary bone tissue, either from the patient or a donor , is used in conjunction with the body's natural bone growth processes to fuse the vertebrae.Fusing of the...
surgery to straighten and stabilize their backs. Osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
is also common in NM.
Respiratory involvement
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 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, hypoventilationHypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
can begin insidiously, and it may cause serious health problems if not remedied by the use of noninvasive mechanical devices to assist breathing, particularly at night.
Communication and eating
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 tubeFeeding tube
A feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by swallowing. The state of being fed by a feeding tube is called gavage, enteral feeding or tube feeding...
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
Hypernasal speech
Rhinolalia , aperta = open, is the medical term for hypernasal speech. The other terms are hyperrhinolalia and open nasality. Hypernasality is a disorder of nasal speech when the sound of the voice is different, an abnormal resonance...
as a result of poor closure of the velopharyngeal port (between the soft palate
Soft palate
The soft palate is the soft tissue constituting the back of the roof of the mouth. The soft palate is distinguished from the hard palate at the front of the mouth in that it does not contain bone....
and the back of the throat). Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and augmentative communication
Augmentative and alternative communication
Augmentative and alternative communication is an umbrella term that encompasses the communication methods used to supplement or replace speech or writing for those with impairments in the production or comprehension of spoken or written language...
devices. Individuals with NM are usually highly sociable and intelligent, with a great desire to communicate.
Nemaline community
In 1999, the first non-medical webpage on nemaline myopathy was launched, and in October 2004, the first Nemaline Myopathy Convention was held in Toronto, Canada. A second convention took place in the summer of 2007 in Edinburgh, Scotland. In March 2006, Niki Shisler released a book, Fragile, in which she recounted her experiences surrounding the birth of twin sons with severe NM.External links
- Nemaline Myopathy Support Group
- Nemaline Myopathy Foundation
- Muscular Dystrophy Association's (MDA) Information Page on Nemaline Myopathy
- A Washington University site delineating the various forms of NM
- GeneReview/NCBI/NIH/UW entry on Nemaline Myopathy
- http://www.buildingstrength.org A Foundation Building Strength Site contains numerous scientific references on the different types of NM, as well as information regarding diagnosis and management and the potential role of tyrosine in patients with Nemaline Myopathy
- Nemaline myopathy Genetic variations described/checked in SNPedia