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Genetics Home Reference: your guide to understanding genetic conditions
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Intranuclear rod myopathy

Reviewed April 2012

What is intranuclear rod myopathy?

Intranuclear rod myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with intranuclear rod myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as "floppy" and may be unable to move on their own.

The severe muscle weakness that occurs in intranuclear rod myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking.

The name intranuclear rod myopathy comes from characteristic abnormal rod-shaped structures that can be seen in the nucleus of muscle cells when muscle tissue is viewed under a microscope.

How common is intranuclear rod myopathy?

Intranuclear rod myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.

What genes are related to intranuclear rod myopathy?

Intranuclear rod myopathy is caused by a mutation in the ACTA1 gene. This gene provides instructions for making a protein called skeletal alpha (α)-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract.

ACTA1 gene mutations that cause intranuclear rod myopathy result in the accumulation of rods of skeletal α-actin in the nucleus of muscle cells. Normally, most actin is found in the fluid surrounding the nucleus (the cytoplasm), with small amounts in the nucleus itself. Researchers suggest that the ACTA1 gene mutations that cause intranuclear rod myopathy may interfere with the normal transport of actin between the nucleus and the cytoplasm, resulting in the accumulation of actin in the nucleus and the formation of intranuclear rods. Abnormal accumulation of actin in the nucleus of muscle cells and a corresponding reduction of available actin in muscle fibers may impair muscle contraction and lead to the muscle weakness seen in intranuclear rod myopathy.

In some people with intranuclear rod myopathy, no ACTA1 gene mutations have been identified. The cause of the disorder in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with intranuclear rod myopathy.

  • ACTA1

How do people inherit intranuclear rod myopathy?

Intranuclear rod myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they 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 intranuclear rod myopathy?

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

  • Genetic Testing Registry: Nemaline myopathy 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834336)

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

You may find the following resources about intranuclear rod 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 intranuclear rod myopathy?

  • intranuclear nemaline rod myopathy
  • nemaline myopathy with exclusively intranuclear rods

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 intranuclear rod myopathy?

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

What glossary definitions help with understanding intranuclear rod myopathy?

actin ; autosomal ; autosomal dominant ; cell ; contraction ; cytoplasm ; gene ; hypotonia ; inherited ; motor ; muscle cells ; muscle tone ; mutation ; myosin ; nucleus ; oxygen ; prevalence ; protein ; respiratory ; rods ; tissue

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

References

  • Feng JJ, Marston S. Genotype-phenotype correlations in ACTA1 mutations that cause congenital myopathies. Neuromuscul Disord. 2009 Jan;19(1):6-16. doi: 10.1016/j.nmd.2008.09.005. Epub 2008 Oct 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18976909?dopt=Abstract)
  • Kaimaktchiev V, Goebel H, Laing N, Narus M, Weeks D, Nixon R. Intranuclear nemaline rod myopathy. Muscle Nerve. 2006 Sep;34(3):369-72. (http://www.ncbi.nlm.nih.gov/pubmed/16477620?dopt=Abstract)
  • Koy A, Ilkovski B, Laing N, North K, Weis J, Neuen-Jacob E, Mayatepek E, Voit T. Nemaline myopathy with exclusively intranuclear rods and a novel mutation in ACTA1 (Q139H). Neuropediatrics. 2007 Dec;38(6):282-6. doi: 10.1055/s-2008-1065356. (http://www.ncbi.nlm.nih.gov/pubmed/18461503?dopt=Abstract)
  • Laing NG, Dye DE, Wallgren-Pettersson C, Richard G, Monnier N, Lillis S, Winder TL, Lochmüller H, Graziano C, Mitrani-Rosenbaum S, Twomey D, Sparrow JC, Beggs AH, Nowak KJ. Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Hum Mutat. 2009 Sep;30(9):1267-77. doi: 10.1002/humu.21059. (http://www.ncbi.nlm.nih.gov/pubmed/19562689?dopt=Abstract)
  • Ochala J. Thin filament proteins mutations associated with skeletal myopathies: defective regulation of muscle contraction. J Mol Med (Berl). 2008 Nov;86(11):1197-204. doi: 10.1007/s00109-008-0380-9. Epub 2008 Jun 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18574571?dopt=Abstract)
  • Sparrow JC, Nowak KJ, Durling HJ, Beggs AH, Wallgren-Pettersson C, Romero N, Nonaka I, Laing NG. Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1). Neuromuscul Disord. 2003 Sep;13(7-8):519-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12921789?dopt=Abstract)
  • Weeks DA, Nixon RR, Kaimaktchiev V, Mierau GW. Intranuclear rod myopathy, a rare and morphologically striking variant of nemaline rod myopathy. Ultrastruct Pathol. 2003 May-Jun;27(3):151-4. (http://www.ncbi.nlm.nih.gov/pubmed/12775505?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: April 2012
Published: October 20, 2014