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Congenital fiber-type disproportion

Reviewed July 2010

What is congenital fiber-type disproportion?

Congenital fiber-type disproportion is a disorder that primarily affects skeletal muscles, which are muscles the body uses for movement. People with this disorder typically experience muscle weakness (myopathy) throughout the body, particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis). Affected people may have joint deformities (contractures) and an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Approximately 30 percent of people with this disorder experience mild to severe breathing problems related to weakness of muscles needed for breathing. Some people who experience these breathing problems require extra support and use a detachable mask (noninvasive mechanical ventilation) to help them breathe at night, and occasionally during the day as well. About 30 percent of affected individuals have difficulty swallowing due to muscle weakness in the throat. Rarely, people with this condition have a weakened and enlarged heart muscle (dilated cardiomyopathy).

The severity of congenital fiber-type disproportion varies widely. It is estimated that up to 25 percent of affected individuals experience severe muscle weakness at birth and die in infancy or childhood. Others have only mild muscle weakness that becomes apparent in adulthood. Most often, the signs and symptoms of this condition appear by age 1. The first signs of this condition are usually decreased muscle tone (hypotonia) and muscle weakness. Muscle weakness generally does not worsen over time, and in some cases it may improve. Although motor skills such as standing and walking may be delayed, many affected children eventually learn to walk. These individuals often have less stamina than their peers, but they remain active. Rarely, people with this condition have a progressive decline in muscle strength over time. These individuals may lose the ability to walk and require wheelchair assistance.

How common is congenital fiber-type disproportion?

Congenital fiber-type disproportion is thought to be a rare condition, although its prevalence is unknown.

What genes are related to congenital fiber-type disproportion?

Mutations in the TPM3, ACTA1, RYR1 and SEPN1 genes can cause congenital fiber-type disproportion. These genes provide instructions for making proteins that are involved in the tensing of muscle fibers (muscle contraction). Changes in these proteins may lead to impaired muscle contraction, resulting in muscle weakness. TPM3 gene mutations are the most common cause of congenital fiber-type disproportion.

Skeletal muscle is made up of two types of muscle fibers: type I (slow twitch fibers) and type II (fast twitch fibers). Normally, type I and type II fibers are the same size. In people with congenital fiber-type disproportion, type I skeletal muscle fibers are significantly smaller than type II skeletal muscle fibers. It is unclear whether the small type I skeletal muscle fibers contribute to the muscle weakness seen in this disorder.

Some people with congenital fiber-type disproportion do not have identified mutations in the TPM3, ACTA1, RYR1 or SEPN1 genes. In these individuals, the cause of the disorder is unknown. Researchers are looking for other genes that are associated with congenital fiber-type disproportion.

Related Gene(s)

Changes in these genes are associated with congenital fiber-type disproportion.

  • ACTA1
  • RYR1
  • SEPN1
  • TPM3

How do people inherit congenital fiber-type disproportion?

Congenital fiber-type disproportion has several different inheritance patterns.

When this condition is caused by mutations in the ACTA1 gene, it usually occurs in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. When congenital fiber-type disproportion is caused by mutations in the ACTA1 gene, it is often the result of a new mutation and occurs in people with no history of the disorder in their family.

Cases of congenital fiber-type disproportion that result from mutations in the RYR1 or SEPN1 gene have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance 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.

When this condition is caused by mutations in the TPM3 gene, it can occur in either an autosomal dominant or autosomal recessive pattern. Many cases of the autosomal dominant type result from new mutations in the TPM3 gene and occur in people with no history of the disorder in their family.

In rare cases, this condition can be inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. The gene or genes on the X chromosome that cause X-linked congenital fiber-type disproportion have not been identified. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of congenital fiber-type disproportion?

These resources address the diagnosis or management of congenital fiber-type disproportion and may include treatment providers.

  • Gene Review: Congenital Fiber-Type Disproportion (http://www.ncbi.nlm.nih.gov/books/NBK1259)
  • Genetic Testing Registry: Congenital myopathy with fiber type disproportion (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0546264)
  • MedlinePlus Encyclopedia: Contracture Deformity (http://www.nlm.nih.gov/medlineplus/ency/article/003185.htm)
  • MedlinePlus Encyclopedia: Hypotonia (http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm)

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

You may find the following resources about congenital fiber-type disproportion 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 congenital fiber-type disproportion?

  • CFTD
  • CFTDM
  • congenital myopathy with fiber type disproportion

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 congenital fiber-type disproportion?

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

What glossary definitions help with understanding congenital fiber-type disproportion?

autosomal ; autosomal dominant ; autosomal recessive ; cardiomyopathy ; cell ; chromosome ; congenital ; contraction ; decreased muscle tone ; difficulty swallowing ; dilated ; gene ; hypotonia ; inheritance ; inherited ; joint ; lordosis ; motor ; muscle tone ; mutation ; new mutation ; ophthalmoplegia ; pattern of inheritance ; prevalence ; ptosis ; recessive ; scoliosis ; sex chromosomes ; skeletal muscle ; type I skeletal muscle fibers

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

References

  • Clarke NF, Kidson W, Quijano-Roy S, Estournet B, Ferreiro A, Guicheney P, Manson JI, Kornberg AJ, Shield LK, North KN. SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Ann Neurol. 2006 Mar;59(3):546-52. (http://www.ncbi.nlm.nih.gov/pubmed/16365872?dopt=Abstract)
  • Clarke NF, Kolski H, Dye DE, Lim E, Smith RL, Patel R, Fahey MC, Bellance R, Romero NB, Johnson ES, Labarre-Vila A, Monnier N, Laing NG, North KN. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann Neurol. 2008 Mar;63(3):329-37. doi: 10.1002/ana.21308. (http://www.ncbi.nlm.nih.gov/pubmed/18300303?dopt=Abstract)
  • Clarke NF, North KN. Congenital fiber type disproportion--30 years on. J Neuropathol Exp Neurol. 2003 Oct;62(10):977-89. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14575234?dopt=Abstract)
  • Clarke NF, Waddell LB, Cooper ST, Perry M, Smith RL, Kornberg AJ, Muntoni F, Lillis S, Straub V, Bushby K, Guglieri M, King MD, Farrell MA, Marty I, Lunardi J, Monnier N, North KN. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat. 2010 Jul;31(7):E1544-50. doi: 10.1002/humu.21278. (http://www.ncbi.nlm.nih.gov/pubmed/20583297?dopt=Abstract)
  • Gene Review: Congenital Fiber-Type Disproportion (http://www.ncbi.nlm.nih.gov/books/NBK1259)
  • Imoto C, Nonaka I. The significance of type 1 fiber atrophy (hypotrophy) in childhood neuromuscular disorders. Brain Dev. 2001 Aug;23(5):298-302. (http://www.ncbi.nlm.nih.gov/pubmed/11504599?dopt=Abstract)
  • Laing NG, Clarke NF, Dye DE, Liyanage K, Walker KR, Kobayashi Y, Shimakawa S, Hagiwara T, Ouvrier R, Sparrow JC, Nishino I, North KN, Nonaka I. Actin mutations are one cause of congenital fibre type disproportion. Ann Neurol. 2004 Nov;56(5):689-94. (http://www.ncbi.nlm.nih.gov/pubmed/15468086?dopt=Abstract)
  • Lawlor MW, Dechene ET, Roumm E, Geggel AS, Moghadaszadeh B, Beggs AH. Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Hum Mutat. 2010 Feb;31(2):176-83. doi: 10.1002/humu.21157. (http://www.ncbi.nlm.nih.gov/pubmed/19953533?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: July 2010
Published: October 20, 2014