Tags: mobile edit mobile web edit |
|
| Line 1: |
Line 1: |
| {{about|a type of spinal muscular atrophy linked to a genetic defect in the [[androgen receptor|AR]] gene|a list of other conditions with similar names|Spinal muscular atrophies}} | | {{Short description|A genetic disorder affecting motor neurons}} |
| | {{Use dmy dates|date=October 2023}} |
|
| |
|
| {{Infobox medical condition (new)
| | '''Spinal and bulbar muscular atrophy''' (SBMA), also known as '''Kennedy's disease''', is a rare, X-linked recessive genetic disorder characterized by the progressive degeneration of motor neurons in the spinal cord and brainstem. This condition primarily affects males, with onset typically occurring in adulthood. |
| | name = Spinal and bulbar muscular atrophy
| |
| | image = X-linked recessive.svg
| |
| | caption = SBMA is inherited in an [[sex linkage|X-linked]] recessive pattern.
| |
| | pronounce =
| |
| | field =
| |
| | synonyms = spinobulbar muscular atrophy, bulbo-spinal atrophy, X-linked bulbospinal neuropathy (XBSN), X-linked spinal muscular atrophy type 1 (SMAX1), Kennedy's disease (KD), and many other names<ref>{{Cite journal|title = Analysis of inconsistencies in terminology of spinal and bulbar muscular atrophy and its effect on retrieval of research|journal = Journal of the Medical Library Association : JMLA|date = 2013-04-01|issn = 1536-5050|pmc = 3634378|pmid = 23646030|pages = 147–150|volume = 101|issue = 2|doi = 10.3163/1536-5050.101.2.010|first = Shelley|last = Arvin}}</ref>
| |
| || symptoms = Muscles cramps<ref name=web/>
| |
| | complications =
| |
| | onset =
| |
| | duration =
| |
| | types =
| |
| | causes = Mutation in the AR gene<ref name=nih/>
| |
| | risks =
| |
| | diagnosis = Clinical features, Family history<ref name=gene/>
| |
| | differential =
| |
| | prevention =
| |
| | treatment = Physical therapy <ref name=gene/>
| |
| | medication =
| |
| | prognosis =
| |
| | frequency =
| |
| | deaths =
| |
| }}
| |
| '''Spinal and bulbar muscular atrophy''' ('''SBMA'''), popularly known as '''Kennedy's disease''', is a progressive debilitating [[neurodegenerative disorder]] resulting in muscle cramps and progressive weakness due to degeneration of [[motor neuron]]s in the [[brainstem]] and [[spinal cord]].<ref name="nih">{{Cite web|url=https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy|title=Spinal and bulbar muscular atrophy|date=2016-03-21|website=Genetics Home Reference|access-date=2016-03-23}}</ref> | |
|
| |
|
| The condition is associated with [[mutation]] of the [[androgen receptor]] (''AR'') gene<ref name=kennedy>{{Cite journal | last1 = Krivickas | first1 = L. S. | title = Amyotrophic lateral sclerosis and other motor neuron diseases | doi = 10.1016/S1047-9651(02)00119-5 | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 14 | issue = 2 | pages = 327–345 | year = 2003 | pmid = 12795519| pmc = }}</ref><ref name="isbn0-12-369462-0">{{cite book |vauthors=Chen CJ, Fischbeck KH |editor1=Tetsuo Ashizawa |editor2=Wells, Robert V. | title = Genetic Instabilities and Neurological Diseases | edition = 2nd | publisher = Academic Press | location = Boston | year = 2006 | pages = 211–222 | isbn = 978-0-12-369462-1 | chapter = Ch. 13: Clinical aspects and the genetic and molecular biology of Kennedy's disease }}</ref> and is inherited in an [[X-linked recessive inheritance|X-linked recessive]] manner. As with many [[genetic disorder]]s, no cure is known, although research continues. Because of its [[endocrine]] manifestations related to the impairment of the ''AR'' gene, SBMA can be viewed as a variation of the disorders of the [[androgen insensitivity syndrome]] (AIS). It is also related to other [[neurodegeneration|neurodegenerative]] diseases caused by similar mutations, such as [[Huntington's disease]].<ref name=BrowneBea2004>{{cite journal|vauthors=Browne SE, Beal MF|title=The energetics of Huntington's disease|journal=Neurochem Res|volume=29|issue=3|pages=531–46|date=Mar 2004|pmid=15038601|type=Review|doi=10.1023/b:nere.0000014824.04728.dd}}</ref>
| | ==Pathophysiology== |
| | | SBMA is caused by a mutation in the [[androgen receptor]] (AR) gene located on the X chromosome. This mutation involves an expansion of a CAG trinucleotide repeat within the gene, leading to the production of an abnormal protein that accumulates in motor neurons, causing their dysfunction and eventual death. The disease is classified as a polyglutamine (polyQ) disorder, similar to [[Huntington's disease]]. |
| ==Signs and symptoms==
| |
| Individuals with SBMA have muscle cramps and progressive weakness due to [[Degeneration (medical)|degeneration]] of motor neurons in the brain stem and spinal cord. Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. The syndrome has neuromuscular and [[endocrine]] manifestations.<ref name="web">{{Cite web|url=https://rarediseases.info.nih.gov/gard/6818/kennedy-disease/resources/1|title=Kennedy disease {{!}} Disease {{!}} Overview {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|access-date=2016-03-23}}</ref>
| |
| | |
| ===Neuromuscular===
| |
| Early signs often include weakness of tongue and mouth muscles, [[fasciculations]], and gradually increasing weakness of limb muscles with muscle wasting. Neuromuscular management is supportive, and the disease progresses very slowly, but can eventually lead to extreme disability.<ref>{{Cite journal|last=Grunseich|first=Christopher|last2=Fischbeck|first2=Kenneth H.|date=2015-11-01|title=Spinal and Bulbar Muscular Atrophy|journal=Neurologic Clinics|volume=33|issue=4|pages=847–854|doi=10.1016/j.ncl.2015.07.002|issn=1557-9875|pmc=4628725|pmid=26515625}}</ref> Further signs and symptoms include:
| |
| [[File:Human chromosome X - 550 bphs.png|150px|thumb|Ideogram of human X chromosome.]]
| |
| {{columns-list|colwidth=30em|
| |
| '''Neurological'''
| |
| * Bulbar signs: bulbar muscles are those supplied by the motor nerves from the brain stem, which control swallowing, [[speech]], and other functions of the throat.<ref name=gene/>
| |
| * [[Lower motor neuron]] signs: lower motor neurons are those in the [[brainstem]] and spinal cord that directly supply the muscles, loss of lower motor neurons leads to weakness and wasting of the muscle.<ref name=gene/>
| |
| * [[Respiratory]] musculature weakness<ref name=gene/>
| |
| * Action [[tremor]]<ref name=gene/>
| |
| * Babinski response: when the bottom of the foot is scraped, the toes bend down (an abnormal response would be an upward movement of the toes indicating a problem with higher-level (upper) motor neurons).<ref>{{Cite book|url=https://books.google.com/books?id=QE0SCAAAQBAJ|title=Basic Clinical Anesthesia|last=Sikka|first=Paul K.|last2=Beaman|first2=Shawn T.|last3=Street|first3=James A.|date=2015-04-09|publisher=Springer|page=470|isbn=9781493917372|language=en}}</ref>
| |
| * Decreased or absent deep [[tendon]] reflexes <ref name=gene/>
| |
| | |
| '''Muscular'''
| |
| * [[Cramps]]: muscle spasms<ref name="gene">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK1333/|title=Spinal and Bulbar Muscular Atrophy|last=La Spada|first=Albert|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301508|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora JH|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Fong|editor-first8=Chin-To|editor-last9=Mefford|editor-first9=Heather C.}} Update: July 3, 2014</ref>
| |
| * Muscular atrophy: loss of muscle bulk that occurs when the lower motor neurons do not stimulate the muscle adequately<ref name=gene/>
| |
| | |
| '''Endocrine'''
| |
| * [[Gynecomastia]]: male breast enlargement<ref name=emed/>
| |
| * [[Erectile dysfunction]]<ref name="emed">{{Cite web | url=http://www.medscape.com/viewarticle/715991 | title=Clinical Features of Spinal and Bulbar Muscular Atrophy}}</ref>
| |
| * Reduced [[fertility]]<ref name=emed/>
| |
| * [[Testicular]] atrophy: testicles become smaller and less functional<ref name="omim">{{Cite web|url=https://omim.org/entry/313200|title=OMIM Entry - # 313200 - SPINAL AND BULBAR MUSCULAR ATROPHY, X-LINKED 1; SMAX1|website=omim.org|access-date=2016-03-23}}</ref>
| |
| | |
| '''Other'''
| |
| * Late onset: individuals usually develop symptoms in their late 30s or afterwards (rarely is it seen in adolescence) <ref name=gene/>
| |
| }}
| |
| | |
| ===Homozygous females===
| |
| [[Homozygous]] females, both of whose [[X chromosomes]] have a mutation leading to CAG expansion of the ''AR'' gene, have been reported to show only mild symptoms of muscle cramps and twitching. No endocrinopathy has been described.<ref name=omim/>
| |
| | |
| ==Genetics==
| |
| The genetics of spinal and bulbar muscular atrophy have to do with the mutated [[androgen receptor]] gene located on the [[X chromosome]]. The effects of the mutation may be androgen-dependent, thus only males are fully affected. Females are rarely affected; female carriers tend to have a relatively mild expression of the disease if they show symptoms at all.<ref name=nih/>
| |
|
| |
|
| ==Pathophysiology== | | ==Clinical Features== |
| [[File:2AM9.png|thumb|Androgen receptor]]
| | The clinical manifestations of SBMA include progressive muscle weakness and atrophy, particularly affecting the proximal muscles. Patients often experience difficulty with activities such as climbing stairs, lifting objects, and swallowing. Bulbar symptoms, such as dysarthria and dysphagia, are common due to the involvement of the brainstem motor neurons. |
| The mechanism behind SBMA is caused by expansion of a CAG repeat in the first [[exon]] of the androgen receptor gene ([[trinucleotide repeat]]s). The CAG repeat encodes a [[polyglutamine tract]] in the androgen receptor protein. The greater the expansion of the CAG repeat, the earlier the disease onset and more severe the disease manifestations. The repeat expansion likely causes a toxic gain of function in the receptor protein, since loss of receptor function in [[androgen insensitivity syndrome]] does not cause motor neuron degeneration.<ref>{{Cite journal|last=Adachi|first=H.|last2=Waza|first2=M.|last3=Katsuno|first3=M.|last4=Tanaka|first4=F.|last5=Doyu|first5=M.|last6=Sobue|first6=G.|date=2007-04-01|title=Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy|journal=Neuropathology and Applied Neurobiology|language=en|volume=33|issue=2|pages=135–151|doi=10.1111/j.1365-2990.2007.00830.x|pmid=17359355|issn=1365-2990}}</ref> | |
|
| |
|
| Spinal and bulbar muscular atrophy may share mechanistic features with other disorders caused by polyglutamine expansion, such as [[Huntington's disease]]. No cure for SBMA is known.<ref name="pmid16389310">{{Cite journal | last1 = Merry | first1 = D. E. | title = Animal Models of Kennedy Disease | doi = 10.1602/neurorx.2.3.471 | journal = NeuroRx | volume = 2 | issue = 3 | pages = 471–479 | year = 2005 | pmid = 16389310| pmc =1144490 }}</ref>
| | Other symptoms may include: |
| | * [[Gynecomastia]] |
| | * Testicular atrophy |
| | * Reduced fertility |
| | * Hand tremors |
| | * Muscle cramps |
|
| |
|
| ==Diagnosis== | | ==Diagnosis== |
| In regards to the diagnosis of spinal and bulbar muscular atrophy, the ''AR Xq12'' [[gene]] is the focus. Many mutations are reported and identified as [[missense mutation|missense]]/[[Nonsense mutation|nonsense]], that can be identified with 99.9% accuracy. Test for this gene in the majority of affected patients yields the diagnosis.<ref name=omim/><ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gtr/tests/506183/|title=Spinal and bulbar muscular atrophy X-linked - Tests - GTR - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-03-23}}</ref>
| | Diagnosis of SBMA is confirmed through genetic testing, which identifies the expanded CAG repeat in the AR gene. Electromyography (EMG) and nerve conduction studies may also be used to assess the extent of motor neuron involvement. |
|
| |
|
| ==Management== | | ==Management== |
| In terms of the management of spinal and bulbar muscular atrophy, no cure is known and treatment is supportive. [[Physical medicine and rehabilitation|Rehabilitation]] to slow muscle weakness can prove positive, though the prognosis indicates some individuals will require the use of a wheelchair in later stages of life.<ref>{{Cite web|url=https://www.ninds.nih.gov/Disorders/All-Disorders/Kennedys-Disease-Information-Page|title=Kennedy's Disease Information Page: National Institute of Neurological Disorders and Stroke (NINDS)|website=NIH|access-date=2016-03-23}}</ref>
| | There is currently no cure for SBMA, and treatment is primarily supportive. Management strategies focus on alleviating symptoms and improving quality of life. These may include: |
| | | * Physical therapy to maintain muscle strength and mobility |
| Surgery may achieve correction of the spine, and early surgical intervention should be done in cases where prolonged survival is expected. Preferred nonsurgical treatment occurs due to the high rate of repeated [[dislocation]] of the [[hip]].<ref name=emed/>
| | * Speech therapy for bulbar symptoms |
| | | * Nutritional support to address swallowing difficulties |
| == Prognosis ==
| | * Hormonal therapy to manage androgen-related symptoms |
| A 2006 study followed 223 patients for a number of years. Of these, 15 died, with a median age of 65 years. The authors tentatively concluded that this is in line with a previously reported estimate of a shortened life expectancy of 10–15 years (12 in their data).<ref>{{Cite journal|last=Atsuta|first=Naoki|year=2006|title=Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients|journal=Brain|volume=129|issue=6|pages=1446–1455|doi=10.1093/brain/awl096|pmid=16621916|doi-access=free}}</ref>
| |
| | |
| ==History==
| |
| This disorder was first described by William R. Kennedy in 1968.<ref name="pmid4233749">{{Cite journal | doi = 10.1212/WNL.18.7.671 | last1 = Kennedy | first1 = W. R. | last2 = Alter | first2 = M. | last3 = Sung | first3 = J. H. | title = Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait | journal = Neurology | volume = 18 | issue = 7 | pages = 671–680 | year = 1968 | pmid = 4233749}}</ref> In 1991, it was recognized that the'' AR ''gene is involved in the disease process. The disease is probably more common than originally thought, SBMA prevalence has been estimated at 1:300,000 males.<ref name=gene/>
| |
| | |
| ==See also==
| |
| * [[Spinal muscular atrophies]]
| |
| | |
| ==References==
| |
| {{Reflist}}
| |
|
| |
|
| ==Further reading== | | ==Prognosis== |
| *{{cite journal|last1=Manzano|first1=Raquel|last2=Sorarú|first2=Gianni|last3=Grunseich|first3=Christopher|last4=Fratta|first4=Pietro|last5=Zuccaro|first5=Emanuela|last6=Pennuto|first6=Maria|last7=Rinaldi|first7=Carlo|title=Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease|journal=Journal of Neurology, Neurosurgery & Psychiatry|volume=89|issue=8|year=2018|pages=808–812|issn=0022-3050|doi=10.1136/jnnp-2017-316961|pmid=29353237|pmc=6204939}}
| | The progression of SBMA is typically slow, and life expectancy is not significantly reduced. However, the disease can lead to significant disability over time, impacting daily activities and quality of life. |
| *{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02124057|title=Study of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-03-23}}
| |
| *{{Cite book|url=https://books.google.com/books?id=3FJXUN6Vh44C|title=Reproductive Endocrinology: A Molecular Approach|last=Chedrese|first=P. Jorge|date=2009-06-13|publisher=Springer Science & Business Media|isbn=9780387881867|language=en}}
| |
| *{{Cite journal|last=Rhodes|first=Lindsay E.|last2=Freeman|first2=Brandi K.|last3=Auh|first3=Sungyoung|last4=Kokkinis|first4=Angela D.|last5=Pean|first5=Alison La|last6=Chen|first6=Cheunju|last7=Lehky|first7=Tanya J.|last8=Shrader|first8=Joseph A.|last9=Levy|first9=Ellen W.|date=2009-12-01|title=Clinical features of spinal and bulbar muscular atrophy|journal=Brain|language=en|volume=132|issue=12|pages=3242–3251|doi=10.1093/brain/awp258|issn=0006-8950|pmc=2792370|pmid=19846582}}
| |
|
| |
|
| == External links == | | ==Related pages== |
| {{Medical resources
| | * [[Motor neuron disease]] |
| | DiseasesDB = 7144
| | * [[Genetic disorders]] |
| | ICD10 = {{ICD10|G|12|1|g|10}}
| | * [[Neurodegenerative diseases]] |
| | ICD9 = {{ICD9|335.1}}
| |
| | ICDO =
| |
| | OMIM = 313200
| |
| | MedlinePlus =
| |
| | eMedicineSubj = article
| |
| | eMedicineTopic = 1172604
| |
| | MeshID = D055534
| |
| | Orphanet=481
| |
| }}
| |
| {{Scholia|topic}}
| |
| {{CNS diseases of the nervous system}}
| |
| {{X-linked disorders}}
| |
| {{Trinucleotide repeat disorders}}
| |
| {{Intracellular receptor deficiencies}}
| |
|
| |
|
| {{DEFAULTSORT:Kennedy's Disease}}
| | [[Category:Genetic disorders]] |
| [[Category:Transcription factor deficiencies]]
| | [[Category:Neurological disorders]] |
| [[Category:Endocrine gonad disorders]]
| |
| [[Category:Motor neuron diseases]]
| |
| [[Category:Neuromuscular disorders]] | |
| [[Category:X-linked recessive disorders]] | |
| [[Category:Rare diseases]] | | [[Category:Rare diseases]] |
| {{dictionary-stub1}}
| |
A genetic disorder affecting motor neurons
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, X-linked recessive genetic disorder characterized by the progressive degeneration of motor neurons in the spinal cord and brainstem. This condition primarily affects males, with onset typically occurring in adulthood.
Pathophysiology
SBMA is caused by a mutation in the androgen receptor (AR) gene located on the X chromosome. This mutation involves an expansion of a CAG trinucleotide repeat within the gene, leading to the production of an abnormal protein that accumulates in motor neurons, causing their dysfunction and eventual death. The disease is classified as a polyglutamine (polyQ) disorder, similar to Huntington's disease.
Clinical Features
The clinical manifestations of SBMA include progressive muscle weakness and atrophy, particularly affecting the proximal muscles. Patients often experience difficulty with activities such as climbing stairs, lifting objects, and swallowing. Bulbar symptoms, such as dysarthria and dysphagia, are common due to the involvement of the brainstem motor neurons.
Other symptoms may include:
- Gynecomastia
- Testicular atrophy
- Reduced fertility
- Hand tremors
- Muscle cramps
Diagnosis
Diagnosis of SBMA is confirmed through genetic testing, which identifies the expanded CAG repeat in the AR gene. Electromyography (EMG) and nerve conduction studies may also be used to assess the extent of motor neuron involvement.
Management
There is currently no cure for SBMA, and treatment is primarily supportive. Management strategies focus on alleviating symptoms and improving quality of life. These may include:
- Physical therapy to maintain muscle strength and mobility
- Speech therapy for bulbar symptoms
- Nutritional support to address swallowing difficulties
- Hormonal therapy to manage androgen-related symptoms
Prognosis
The progression of SBMA is typically slow, and life expectancy is not significantly reduced. However, the disease can lead to significant disability over time, impacting daily activities and quality of life.
Related pages
