Facioscapulohumeral muscular dystrophy
| Facioscapulohumeral muscular dystrophy | |
|---|---|
| Timelapse of DUX4 being expressed in FSHD Muscle Cells | |
| Classification and external resources | |
| Specialty | neurology |
| ICD-10 | G71.0 |
| ICD-9-CM | 359.1 |
| OMIM | 158900 158901 |
| DiseasesDB | 7247 |
| MedlinePlus | 000707 |
| eMedicine | neuro/133 |
| Patient UK | Facioscapulohumeral muscular dystrophy |
| MeSH | D020391 |
| GeneReviews | |
| Orphanet | 269 |
Facioscapulohumeral muscular dystrophy (FSHMD, FSHD or FSH)—originally named Landouzy-Dejerine—is a usually autosomal dominant inherited form of muscular dystrophy (MD) that initially affects the skeletal muscles of the face (facio), scapula (scapulo) and upper arms (humeral). FSHD is the third most common genetic disease of skeletal muscle. Orpha.net lists the prevalence as 4/100,000 while a 2014 population-based study in the Netherlands reported a significantly higher prevalence of 12 in 100,000.
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 can be threatened by respiratory insufficiency and up to 20% of affected individuals become severely disabled requiring use of a wheel chair or mobility scooter. In a Dutch study approximately 1% of patients required (nocturnal or diurnal) ventilatory support. Non-muscular symptoms frequently associated with FSHD include subclinical sensorineural hearing loss and retinal telangiectasia. In more than 95% of known cases, the disease is associated with contraction of the D4Z4 repeat in the 4q35 subtelomeric region of Chromosome 4. Seminal research published in August 2010 now shows the disease requires a second mechanism, which for the first time provides a unifying theory for its underlying genetics. The second mechanism is a "toxic gain of function" of the DUX4 gene, which is the first time in genetic research that a "dead gene" has been found to "wake up" and cause disease.
Building on the 2010 unified theory of FSHD, researchers in 2014 published the first proposed pathophysiology definition of the disease and four viable therapeutic targets for possible intervention points.
Because of the extreme variability of the disease, an authoritative and scientifically confirmed set of symptoms does not yet exist. The prevalence is widely placed at 1/20,000, but the exact prevalence is not known. A November 2008 report from Orpha.net, an organization backed by the Institut National de la Santé et de la Recherche Médicale (INSERM), listed the prevalence of 7/100,000 but the May 2014 version of this report places the prevalence at 4/100,000. A 2014 population-based study in the Netherlands reported a significantly higher prevalence of 12 in 100,000.[4]
...
Wikipedia