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Genetics Home Reference: your guide to understanding genetic conditions
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Nemaline myopathy

Reviewed May 2010

What is nemaline myopathy?

Nemaline myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs. This weakness can worsen over time. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). Most people with nemaline myopathy are able to walk, although some affected children may begin walking later than usual. As the condition progresses, some people may require wheelchair assistance. In severe cases, the muscles used for breathing are affected and life-threatening breathing difficulties can occur.

Nemaline myopathy is divided into six types. In order of decreasing severity, the types are: severe congenital, Amish, intermediate congenital, typical congenital, childhood-onset, and adult-onset. The types are distinguished by the age when symptoms first appear and the severity of symptoms; however, there is overlap among the various types. The severe congenital type is the most life-threatening. Most individuals with this type do not survive past early childhood due to respiratory failure. The Amish type solely affects the Old Order Amish population of Pennsylvania and is typically fatal in early childhood. The most common type of nemaline myopathy is the typical congenital type, which is characterized by muscle weakness and feeding problems beginning in infancy. Most of these individuals do not have severe breathing problems and can walk unassisted. People with the childhood-onset type usually develop muscle weakness in adolescence. The adult-onset type is the mildest of all the various types. People with this type usually develop muscle weakness between ages 20 and 50.

How common is nemaline myopathy?

Nemaline myopathy has an estimated incidence of 1 in 50,000 individuals.

What genes are related to nemaline myopathy?

Mutations in at least six genes can cause nemaline myopathy. These genes provide instructions for producing proteins that play important roles in skeletal muscles. Within skeletal muscle cells, these proteins are found in structures called sarcomeres. Sarcomeres are necessary for muscles to tense (contract). Many of the proteins associated with nemaline myopathy interact within the sarcomere to facilitate muscle contraction. When the skeletal muscle cells of people with nemaline myopathy are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain rod-like structures called nemaline bodies.

Most cases of nemaline myopathy with a known genetic cause result from mutations in one of two genes, NEB or ACTA1. NEB gene mutations account for 50 percent of all cases of nemaline myopathy and ACTA1 gene mutations account for 15 to 25 percent of all cases. When nemaline myopathy is caused by NEB gene mutations, signs and symptoms are typically present at birth or beginning in early childhood. When nemaline myopathy is caused by ACTA1 gene mutations, the condition's severity and age of onset vary widely. Mutations in the other four genes associated with nemaline myopathy each account for only a small percentage of cases.

Mutations in any one of the six genes associated with nemaline myopathy lead to disorganization of the proteins found in the sarcomeres of skeletal muscles. The disorganized proteins cannot interact normally, which disrupts muscle contraction. Inefficient muscle contraction leads to muscle weakness and the other features of nemaline myopathy.

Some individuals with nemaline myopathy do not have an identified mutation. The genetic cause of the disorder is unknown in these individuals.

Related Gene(s)

Changes in these genes are associated with nemaline myopathy.

  • ACTA1
  • CFL2
  • NEB
  • TNNT1
  • TPM2
  • TPM3

How do people inherit nemaline myopathy?

Nemaline myopathy is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Less often, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of nemaline myopathy?

These resources address the diagnosis or management of nemaline myopathy and may include treatment providers.

  • Gene Review: Nemaline Myopathy (http://www.ncbi.nlm.nih.gov/books/NBK1288)
  • Genetic Testing Registry: Nemaline myopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0206157)
  • Genetic Testing Registry: Nemaline myopathy 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1836448)
  • Genetic Testing Registry: Nemaline myopathy 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1850569)
  • Genetic Testing Registry: Nemaline myopathy 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834336)
  • Genetic Testing Registry: Nemaline myopathy 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1836447)
  • Genetic Testing Registry: Nemaline myopathy 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1854380)
  • Genetic Testing Registry: Nemaline myopathy 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1836472)
  • Genetic Testing Registry: Nemaline myopathy 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853154)

You might also find information on the diagnosis or management of nemaline myopathy in Educational resources (http://www.ghr.nlm.nih.gov/condition/nemaline-myopathy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/nemaline-myopathy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about nemaline myopathy?

You may find the following resources about nemaline myopathy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for nemaline myopathy?

  • myopathies, nemaline
  • myopathy, nemaline
  • nemaline body disease
  • nemaline rod disease
  • rod body disease
  • rod-body myopathy
  • rod myopathy

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about nemaline myopathy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding nemaline myopathy?

autosomal ; autosomal dominant ; autosomal recessive ; cell ; congenital ; contraction ; gene ; incidence ; inherited ; joint ; muscle cells ; mutation ; population ; recessive ; respiratory ; sarcomere ; scoliosis ; skeletal muscle

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ilkovski B, Clement S, Sewry C, North KN, Cooper ST. Defining alpha-skeletal and alpha-cardiac actin expression in human heart and skeletal muscle explains the absence of cardiac involvement in ACTA1 nemaline myopathy. Neuromuscul Disord. 2005 Dec;15(12):829-35. Epub 2005 Nov 8. (http://www.ncbi.nlm.nih.gov/pubmed/16288873?dopt=Abstract)
  • Lehtokari VL, Pelin K, Sandbacka M, Ranta S, Donner K, Muntoni F, Sewry C, Angelini C, Bushby K, Van den Bergh P, Iannaccone S, Laing NG, Wallgren-Pettersson C. Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum Mutat. 2006 Sep;27(9):946-56. (http://www.ncbi.nlm.nih.gov/pubmed/16917880?dopt=Abstract)
  • Nowak KJ, Sewry CA, Navarro C, Squier W, Reina C, Ricoy JR, Jayawant SS, Childs AM, Dobbie JA, Appleton RE, Mountford RC, Walker KR, Clement S, Barois A, Muntoni F, Romero NB, Laing NG. Nemaline myopathy caused by absence of alpha-skeletal muscle actin. Ann Neurol. 2007 Feb;61(2):175-84. (http://www.ncbi.nlm.nih.gov/pubmed/17187373?dopt=Abstract)
  • Ottenheijm CA, Hooijman P, DeChene ET, Stienen GJ, Beggs AH, Granzier H. Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2). J Struct Biol. 2010 May;170(2):334-43. doi: 10.1016/j.jsb.2009.11.013. Epub 2009 Nov 26. (http://www.ncbi.nlm.nih.gov/pubmed/19944167?dopt=Abstract)
  • Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN. Nemaline myopathy: a clinical study of 143 cases. Ann Neurol. 2001 Sep;50(3):312-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11558787?dopt=Abstract)
  • Wallefeld W, Krause S, Nowak KJ, Dye D, Horváth R, Molnár Z, Szabó M, Hashimoto K, Reina C, De Carlos J, Rosell J, Cabello A, Navarro C, Nishino I, Lochmüller H, Laing NG. Severe nemaline myopathy caused by mutations of the stop codon of the skeletal muscle alpha actin gene (ACTA1). Neuromuscul Disord. 2006 Oct;16(9-10):541-7. Epub 2006 Sep 1. (http://www.ncbi.nlm.nih.gov/pubmed/16945536?dopt=Abstract)
  • Youssef NC, Scola RH, Lorenzoni PJ, Werneck LC. Nemaline myopathy: clinical, histochemical and immunohistochemical features. Arq Neuropsiquiatr. 2009 Sep;67(3B):886-91. (http://www.ncbi.nlm.nih.gov/pubmed/19838523?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2010
Published: November 24, 2014