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Information about Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy
Classification & external resources
NIH map of superficial muscle groups associated with Muscular Dystrophy[1]
ICD-10G71.0
ICD-9359.1
OMIM158900 158901
DiseasesDB7247
MedlinePlus000707
eMedicineneuro/133 


“FSHD” redirects here. For other uses, see FSHD (disambiguation).


Facioscapulohumeral muscular dystrophy (FSHMD, FSHD or FSH), which is also known as Landouzy-Dejerine,[2] is an autosomal dominant form of muscular dystrophy that initially affects the skeletal muscles of the face (facio), scapula (scapulo) and upper arms (humeral). It is the third most common genetic disease of skeletal muscle. Symptoms may develop in early childhood and are usually noticeable in the teenage years with 95% of affected individuals manifesting disease by age 20 years. A progressive skeletal muscle weakness usually develops in other areas of the body as well; often the weakness is asymmetrical. Life expectancy is normal, but up to 15% of affected individuals become severely disabled and eventually must use a wheel chair. Non-muscular symptoms frequently associated with FSHD include subclinical sensorineural hearing loss and retinal telangectasias.

History

Number of FSHD Papers[3]
1900-19500
1951-197530
1976-1990133
1991-1996148
1997-2006294
data from the Entrez-Pubmed database[3]


FSHD was first described in 1884 by French physicians Louis Landouzy and Joseph Dejerine. In their paper of 1886, Landouzy and Dejerine drew attention to the familial nature of the disorder and mentioned that four generations were affected in the kindred that they had investigated.[4] Formal definition of FSHD's clinical features didn't occur until 1952 when a large Utah family with FSHD was studied. Beginning about 1980 an increasing interest in FSHD led to increased understanding of the great variability in the disease and a growing understanding of the genetic and pathophysiological complexities. By the late 1990s, researchers were finally beginning to understand the regions of Chromosome 4 associated with FSHD.[5]

FSHD is also known by the following names:
  • Landouzy-Dejerine[2]
  • Landouzy-Dejerine syndrome[4]
  • Erb-Landouzy-Dejerine syndrome[4]
  • Landouzy-Dejerine dystrophy or atrophy[4]

Pathophysiology

The exact pathophysiology of FSHD remains unknown as of March 2007. Muscle histologic changes are nonspecific for the muscle wasting. There is evidence of early inflammatory changes in the muscle, but reported responses to high dose open labeled corticosteroid treatment have been negative. Animal studies of anabolic effects of beta adrenergic agonists on models of muscle wasting led to an open trial of albuterol (a beta adrenergic agonist) in which limited preliminary results support an improvement of muscle mass and strength in FSHD. Preliminary studies of muscle cultures suggest an increased sensitivity to oxidative stress, but require further exploration.

Genetics

More than 95% of cases of FSHD are associated with the deletion of integral copies of a tandemly repeated 3.2kb unit (D4Z4 repeat) at the subtelomeric region 4q35 of the Human genome of which a normal chromosome will include between 11-150 repititions of D4Z4.[5] There are both heterochromatin and euchromatin structures within D4Z4 but no genes.[5] Inheritance is autosomal dominant, though up to one-third of the cases appear to be the result of de novo (new) mutations. The heterochromatin is specifically lost in the deletions of FSHD while the euchromatin structures remain.[5] If the entire region is removed, there are birth defects, but no specific defects on skeletal muscle. Individuals appear to require the existence of 11 or fewer repeat units to be at risk for FSHD. Though the nature of the DNA mutation is known, it has not been possible to identify a gene or mechanism that causes FSHD and a novel position effect has been postulated to explain the disease phenotype. In addition, a few cases of FSHD are the result of rearrangements between subtelomeric chromosome 4q and a subtelomeric region of 10q that contains a tandem repeat structure highly homologous (95%) to 4q35. Disease occurs when the translocation results in a critical loss of tandem repeats to the 4q site. Finally, there is a large family with a phenotype indistinguishable from FSHD in which no pathological changes at the 4q site or translocation of 4q-10q are found.

Testing

Since the early 2000s genetic testing that measures the size of the D4Z4 deletions on 4q35 has become the preferred mechanism for confirming the presence of FSHD. As of 2007, this test is considered highly accurate but is still performed by a limited set of labs in the US. However, because the test is expensive, patients and doctors may still rely on one or more of the following tests, all of which are far less accurate and specific than the genetic test:[6]
  • Creatine kinase (CK) level: This test measures the Creatine kinase enzyme in the blood. Elevated levels of CK are related to muscle atrophy.
  • electromyogram (EMG): This test measures the electrical activity in the muscle
  • nerve conduction velocity (NCV): This test measures the how fast signals travel from one part of a nerve to another. The nerve signals are measured with surface electrodes (similar to those used for an electrocardiogram), and the test is only slightly uncomfortable.
  • muscle biopsy: Through outpatient surgery a small piece of muscle is removed (usually from the arm or leg) and evaluated with a variety of biochemical tests. Researchers are attempting to match results of muscle biopsies with DNA tests to better understand how variations in the genome present themselves in tissue anomalies.

Symptoms and prevalence

Because of the extreme variability of the disease, an authoritative and scientifically confirmed set of symptoms does not yet exist. The prevalence is widely quoted to be 1/20,000, but the exact prevalence is not known.
  • Facial muscle weakness (eyelid drooping, inability to whistle, decreased facial expression, depressed or angry facial expression, difficulty pronouncing the letters M, B, and P)
  • Shoulder weakness (difficulty working with the arms raised, sloping shoulder)
  • Hearing loss
  • Abnormal heart rhythm
  • Unequal weakening of the biceps, triceps, deltoids, and lower arm muscles
  • Loss of strength in stomach muscles and eventual progression to the legs
  • Foot drop

Compounds of interest

ACVR2B is a compound identified in 2005/2006 by Johns Hopkins. It increased muscle mass in a non-Muscular Dystrophy Mouse by up to 60% in two weeks.

Treatment

  • No Food and Drug Administration approved therapies exist specifically for FSHD.
  • Occupational therapy can sometimes be used to help cope with new devices to make things easier.

MY0-029

Main article: Stamulumab
MYO-029 is an experimental myostatin inhibiting drug developed by Wyeth Pharmaceuticals for the treatment of muscular dystrophy. Myostatin is a protein that inhibits the growth of muscle tissue, MYO-029 is a recombinant human antibody designed to bind and inhibit the activity of myostatin.[7] A 2005/2006 study was completed by Wyeth in Collegeville, PA and included participants afflicted with FSHD.

Procedures used to improve quality of life

  • Scapular fusion: surgical fusion of the scapula to the thorax.
  • Scapular bracing: a scapular brace helps stabilize the shoulder and correct glenohumeral positioning.

References

1. ^ Encyclopedia Entry for Muscular Dystrophy, NIH's, MedlinePlus, Update as of 9/10/2006
2. ^ disease overview, MDA, date accessed 6 March 2007
3. ^ "FSHSociety Update: 2006 Year in Review - Your Dollars at Work", FSH Society, Fall 2006
4. ^ Landouzy-Dejerine syndrome, whonamedit.com, date accessed March 11, 2007
5. ^ Impossible Things: Through the looking glass with FSH Dystrophy Researchers, Margaret Wahl, MDA, Quest magazine, Vol 14, No 2, March-April 2007
6. ^ FSHD Fact Sheet, MDA, 11/1/2001
7. ^ [1]

Other

  • Meena Upadhyaya & David N. Cooper ed., FSHD Facioscapulohumeral Muscular Dystrophy: Clinical Medicine and Molecular Cell Biology, BIOS Scientific Publishers, Taylor and Francis Group, First Edition (2004), ISBN 1-85996-244-0.

External links

See also

 •  • [ e]
Muscular Dystrophy
The Nine Primary Muscular DystrophiesBecker's • Congenital • Duchenne • Distal • Emery-Dreifuss • Facioscapulohumeral • Limb-girdle muscular dystrophy • Myotonic • Oculopharyngeal
Related topics
National/International OrganizationsMuscular Dystrophy Association (USA) . Muscular Dystrophy Canada
US government Institutes and LegislationNINDS • NIAMS • NICHD • MD CARE Act • Genetic Information Nondiscrimination Act • Americans with Disabilities Act of 1990
National/International EventsJerry Lewis MDA Telethon (USA)
Recent or Ongoing Clinical TrialsStamulumab (MYO-029)
For other uses of "ICD", see ICD (disambiguation).


The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD
..... Click the link for more information.
List of ICD-10 codes. The version for 2007 is available online at [1]

Chapter Blocks Title
I Certain infectious and parasitic diseases
II Neoplasms
III Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism
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For other uses of "ICD", see ICD (disambiguation).


The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD
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The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. These codes are in the public domain.

See also


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The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications.

It directly integrates the Unified Medical Language System.

External links

  • Diseases Database

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MedlinePlus is a website containing health information from the world's largest medical library, the United States National Library of Medicine. The site is intended to be used by health care providers and patients, and designed to provide up-to-date, authoritative information.
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eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely, two medical doctors. It was sold to WebMD in January 2006.
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FSHD may refer to:
  • Facioscapulohumeral muscular dystrophy
  • Family Studies and Human Development, a type of degree in higher education

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Muscular Dystrophy
Classification & external resources

ICD-10 G 71.0
ICD-9 359.0 - 359.1

MedlinePlus 001190
eMedicine orthoped/418  
MeSH D009136 Muscular dystrophy
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Skeletal muscle is a type of striated muscle, usually attached to the skeleton. Skeletal muscles are used to create movement, by applying force to bones and joints; via contraction.
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The face is the front part of the head, in humans from the forehead to chin including the hair, forehead, eyebrow, eyes, nose, cheeks, mouth, lips, philtrum, teeth, skin, and chin. The face is used for expression, appearance and identity amongst others.
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scapula, or shoulder blade, is the bone that connects the humerus (arm bone) with the clavicle (collar bone).

The scapula forms the posterior part of the shoulder girdle. In humans, it is a flat bone, roughly triangular in shape.
..... Click the link for more information.
The humerus is a long bone in the arm or fore-legs (animals) that runs from the shoulder to the elbow. On a skeleton, it fits between the scapula and the ulna. It consists of the following three sections:
  • Upper extremity of humerus
  • Body of humerus

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A genetic disorder is a condition caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due to genetic abnormalities acquired in a few cells during life, the term "genetic disease" most commonly refers to diseases present in all cells of the body
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MUSCLE (multiple sequence comparison by log-expectation) is public domain, multiple sequence alignment software for protein and nucleotide sequences.
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Homo.
Upper Paleolithic 33 At age 15: 39 (to age 54)[3][4]
Neolithic 20  
Bronze Age 18[5]  
Classical Greece 25-45  
Classical Rome 25-45  
Medieval Britain 20-30  
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A wheelchair is a wheeled mobility device in which the user sits. The device is propelled either manually (by pushing the wheels with the hands) or via various automated systems.
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MeSH D013684 Telangiectasias, or spider veins, are small dilated blood vessels near the surface of the skin; usually they measure only a few millimeters. They can develop anywhere on the body but commonly on the face around the nose, cheeks, and chin.
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18th century - 19th century - 20th century
1850s  1860s  1870s  - 1880s -  1890s  1900s  1910s
1881 1882 1883 - 1884 - 1885 1886 1887

:
Subjects:     Archaeology - Architecture -
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19th century - 20th century - 21st century
1920s  1930s  1940s  - 1950s -  1960s  1970s  1980s
1949 1950 1951 - 1952 - 1953 1954 1955

Year 1952 (MCMLII
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Pathophysiology is the study of the disturbance of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from a disease or abnormal syndrome or condition that may not qualify to be called a disease.
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Histology (from the Greek ἱστός) is the study of tissue sectioned as a thin slice, using a microtome. It can be described as microscopic anatomy.
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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood
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Salbutamol (INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and Chronic obstructive pulmonary disease.
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Telomeres are specialized protein-DNA constructs present at the ends of eukaryotic chromosomes, which prevent them from degradation and end-to-end chromosomal fusion. To conceptually introduce them, introductory biology courses often describe them as a type of chromosomal aglet.
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human genome is the genome of Homo sapiens, which is composed of 24 distinct pairs of chromosomes (22 autosomal + X + Y) with a total of approximately 3 billion DNA base pairs containing an estimated 20,000–25,000 genes.
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Heterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited.

Structure

Chromatin is found in two varieties: euchromatin and heterochromatin.
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Euchromatin is a lightly packed form of chromatin that is rich in gene concentration, and is often (but not always) under active transcription. Unlike heterochromatin, it is found in both eukaryotes and prokaryotes.
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dominance relationship refers to how the alleles for a locus interact to produce a phenotype.

There are three main kinds of dominance relationships:
  • Simple dominance or complete dominance (simple Mendelian inheritance) over a recessive trait

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mutations are changes to the base pair sequence of the genetic material of an organism. Mutations can be caused by copying errors in the genetic material during cell division, by exposure to ultraviolet or ionizing radiation, chemical mutagens, or viruses, or can occur deliberately
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