Global InformationFacioscapulohumeral muscular dystrophy information
| Facioscapulohumeral muscular dystrophy | |
|---|---|
| Other names | Landouzy–Dejerine muscular dystrophy, FSHMD, FSH |
 | |
| A diagram showing the muscles commonly affected by FSHD | |
| Pronunciation |
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| Specialty | Neurology, neuromuscular medicine |
| Symptoms | Facial weakness, scapular winging, foot drop |
| Complications | Chronic pain, dry eyes, and shoulder instability; less commonly retinal disease, scoliosis, and respiratory insufficiency |
| Usual onset | Ages 15 – 30 years |
| Duration | Lifelong |
| Types | Typically classified by genetic cause (FSHD1, FSHD2). Sometimes classified by disease manifestation (eg, infantile-onset) |
| Causes | Genetic (inherited or new mutation) |
| Risk factors | Male sex, extent of genetic mutation |
| Diagnostic method | Genetic testing |
| Differential diagnosis | Limb-girdle muscular dystrophy (especially calpainopathy), Pompe disease, mitochondrial myopathy, polymyositis[2] |
| Management | Physical therapy, bracing, reconstructive surgery |
| Medication | Clinical trials ongoing |
| Prognosis | Progressive, unaffected life expectancy |
| Frequency | Up to 1/8,333[2] |
Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy, a group of heritable diseases that cause degeneration of muscle and progressive weakness. Per the name, FSHD tends to sequentially weaken the muscles of the face, those that position the scapula, and those overlying the humerus bone of the upper arm.[2][3] These areas can be spared, and muscles of other areas usually are affected, especially those of the chest, abdomen, spine, and shin. Almost any skeletal muscle can be affected in advanced disease. Abnormally positioned, termed 'winged', scapulas are common, as is the inability to lift the foot, known as foot drop. The two sides of the body are often affected unequally. Weakness typically manifests at ages 15 – 30 years.[4] FSHD can also cause hearing loss and blood vessel abnormalities at the back of the eye.
FSHD is caused by a genetic mutation leading to deregulation of the DUX4 gene.[5] Normally, DUX4 is expressed (i.e., turned on) only in select human tissues, most notably in the very young embryo. In the remaining tissues, it is repressed (i.e., turned off).[6][7] In FSHD, this repression fails in muscle tissue, allowing sporadic expression of DUX4 throughout life. Deletion of DNA in the region surrounding DUX4 is the causative mutation in 95% of cases, termed "D4Z4 contraction" and defining FSHD type 1 (FSHD1).[8] FSHD caused by other mutations is FSHD type 2 (FSHD2). For disease to develop, also required is a 4qA allele, which is a common variation in the DNA next to DUX4. The chances of a D4Z4 contraction with a 4qA allele being passed on to a child is 50% (autosomal dominant);[2] in 30% of cases, the mutation arose spontaneously.[4] Mutations of FSHD cause inadequate DUX4 repression by unpacking the DNA around DUX4, making it accessible to be copied into messenger RNA (mRNA). The 4qA allele stabilizes this DUX4 mRNA, allowing it to be used for production of DUX4 protein.[9] DUX4 protein is a modulator of hundreds of other genes, many of which are involved in muscle function.[2][5] How this genetic modulation causes muscle damage remains unclear.[2]
Signs, symptoms, and diagnostic tests can suggest FSHD; genetic testing usually provides definitive diagnosis.[2] FSHD can be presumptively diagnosed in an individual with signs/symptoms and an established family history. No intervention has proven effective for slowing progression of weakness.[10] Screening allows for early detection and intervention for various disease complications. Symptoms can be addressed with physical therapy, bracing, and reconstructive surgery such as surgical fixation of the scapula to the thorax.[11] FSHD affects up to 1 in 8,333 people,[2] putting it in the three most common muscular dystrophies with myotonic dystrophy and Duchenne muscular dystrophy.[12][13] Prognosis is variable. Many are not significantly limited in daily activity, whereas a wheel chair or scooter is required in 20% of cases.[14] Life expectancy is not affected, although death can rarely be attributed to respiratory insufficiency due to FSHD.[15]
FSHD was first distinguished as a disease in the 1870s and 1880s when French physicians Louis Théophile Joseph Landouzy and Joseph Jules Dejerine followed a family affected by it, thus the initial name Landouzy–Dejerine muscular dystrophy. Their work is predated by descriptions of probable individual FSHD cases.[16][17][18] The significance of D4Z4 contraction on chromosome 4 was established in the 1990s. The DUX4 gene was discovered in 1999, found to be expressed and toxic in 2007, and in 2010 the genetic mechanism causing its expression was elucidated. In 2012, the gene most frequently mutated in FSHD2 was identified. In 2019, the first drug designed to counteract DUX4 expression entered clinical trials.[19]
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The sources listed below differ on pronunciation of the 'u' in 'scapulo'. A 'long u' sound in an unstressed nonfinal syllable is often reduced to a schwa and varies by speaker.
- "Facioscapulohumeral". Merriam-Webster.com Dictionary.
- "Facioscapulohumeral". Medical Dictionary, Farlex and Partners, 2009.
- ^ a b c d e f g h Wagner KR (December 2019). "Facioscapulohumeral Muscular Dystrophies". CONTINUUM: Lifelong Learning in Neurology. 25 (6): 1662–1681. doi:10.1212/CON.0000000000000801. PMID 31794465. S2CID 208531681.
- ^ Stedman T (1987). Webster's New World/Stedman's Concise Medical Dictionary (1 ed.). Baltimore: Williams & Wilkins. p. 230. ISBN 0-13-948142-7.
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- ^ De Iaco A, Planet E, Coluccio A, Verp S, Duc J, Trono D (June 2017). "DUX-family transcription factors regulate zygotic genome activation in placental mammals". Nature Genetics. 49 (6): 941–945. doi:10.1038/ng.3858. PMC 5446900. PMID 28459456.
- ^ Snider L, Geng LN, Lemmers RJ, Kyba M, Ware CB, Nelson AM, Tawil R, Filippova GN, van der Maarel SM, Tapscott SJ, Miller DG (28 October 2010). "Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene". PLOS Genetics. 6 (10): e1001181. doi:10.1371/journal.pgen.1001181. PMC 2965761. PMID 21060811.
- ^ Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, Snider L, Straasheijm KR, van Ommen GJ, Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM (19 August 2010). "A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy" (PDF). Science. 329 (5999): 1650–3. Bibcode:2010Sci...329.1650L. doi:10.1126/science.1189044. hdl:1887/117104. PMC 4677822. PMID 20724583. Archived from the original (PDF) on 2014-06-05.
- ^ Lemmers RJ, Wohlgemuth M, van der Gaag KJ, et al. (November 2007). "Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophy". Am. J. Hum. Genet. 81 (5): 884–94. doi:10.1086/521986. PMC 2265642. PMID 17924332.
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Eren2020ScapFusionStagingwas invoked but never defined (see the help page). - ^ Theadom A, Rodrigues M, Roxburgh R, Balalla S, Higgins C, Bhattacharjee R, Jones K, Krishnamurthi R, Feigin V (2014). "Prevalence of muscular dystrophies: a systematic literature review". Neuroepidemiology. 43 (3–4): 259–68. doi:10.1159/000369343. hdl:10292/13206. PMID 25532075. S2CID 2426923.
- ^ Mah JK, Korngut L, Fiest KM, Dykeman J, Day LJ, Pringsheim T, Jette N (January 2016). "A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies". The Canadian Journal of Neurological Sciences. 43 (1): 163–77. doi:10.1017/cjn.2015.311. PMID 26786644. S2CID 24936950.
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