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| __NOTOC__ | | __NOTOC__ |
| {{Infobox_Disease |
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| Name = Tuberous sclerosis|
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| Image = TuberousSclerosis-Rayer.jpg|
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| Caption = Earliest illustration, from [[Pierre François Olive Rayer|Rayer]]'s atlas of skin diseases, 1835.|
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| }}
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| {{Tuberous sclerosis}} | | {{Tuberous sclerosis}} |
| | {{CMG}}; {{AE}} {{Jose}} |
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| '''For patient information on this page, click [[Tuberous sclerosis (patient information)|here]]'''
| | ==[[Tuberous sclerosis overview|Overview]]== |
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| {{CMG}}; {{AE}} {{RT}}
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| {{SK}} Tuberous sclerosis complex, TSC, Bourneville disease, Bourneville-Pringle syndrome, epiloia
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| ==Natural History, Complications, Prognosis==
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| ===Natural History===
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| * Those individuals with mild symptoms generally do well and live long productive lives, while individuals with the more severe form may have serious disabilities.
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| * However, with appropriate medical care, most individuals with the disorder can look forward to normal life expectancy.<ref name="TSFactSheet"/>
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| ===Complications===
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| * [[Cardiac failure]] due to [[rhabdomyomas]]
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| * [[Bronchopneumonia]]
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| * [[Lymphangiomyomatosis]] of the lung is only a risk for females with AMLs.<ref name="Rakowski2006">{{cite journal
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| | author = Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA.
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| | title = Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors.
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| | journal = Kidney International
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| | volume =
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| | issue =
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| | pages =
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| | year = 2006
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| | id = PMID 17003820
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| }}</ref>
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| * [[Renal failure]]
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| * [[Autosomal dominant]] [[polycystic kidney disease]] in 2 % patients.
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| * [[Angiomyolipoma]] (AML) and cysts in [[kidneys]] are common, and more frequent in females than males and in TSC2 than TSC1.<ref name="shepherd1991">{{cite journal
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| | author = Shepherd C, Gomez M, Lie J, Crowson C
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| | title = Causes of death in patients with tuberous sclerosis.
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| | journal = Mayo Clin Proc
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| | volume = 66
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| | issue = 8
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| | pages = 792-6
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| | year = 1991
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| | id = PMID 1861550
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| }}</ref>
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| * [[Renal cell carcinoma]] is uncommon.
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| * [[Brain tumor]]
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| * [[Status epilepticus]]
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| * Subependymal giant cell astrocytomas (SEGA)
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| * [[Hydrocephalus]]
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| ===Prognosis===
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| * The prognosis for individuals with TSC depends on the severity of symptoms, which range from mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe mental retardation, uncontrollable seizures, and [[kidney failure]].
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| == Diagnosis ==
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| There are no [[pathognomonic]] clinical [[medical sign|signs]] for [[tuberous sclerosis]]. Many signs are present in individuals who are healthy (although rarely), or who have another disease. A combination of signs, classified as major or minor, is required in order to establish a clinical diagnosis.
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| {| class=wikitable width="75%" style="margin: 1em auto 1em auto"
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| |+ Diagnostic Criteria for Tuberous Sclerosis Complex<ref name="PMID15563009">{{cite journal
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| | author = Roach E, Sparagana S
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| | title = Diagnosis of tuberous sclerosis complex.
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| | journal = Journal of Child Neurology
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| | volume = 19
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| | issue = 9
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| | pages = 643-9
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| | year = 2004
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| | id = PMID 15563009
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| | url = http://www.medscape.com/viewarticle/495642
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| }}</ref>
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| ! colspan="5" width="100%" | Major Features
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| |-
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| ! width="2%" |
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| ! width="12%" | Location
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| ! width="42%" | Sign
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| ! width="22%" | Onset<ref name="PMID17005952">{{cite journal
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| | author = Crino P, Nathanson K, Henske E
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| | title = The Tuberous Sclerosis Complex.
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| | journal = New England Journal of Medicine
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| | volume = 355
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| | issue = 13
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| | pages = 1345-56
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| | year = 2006
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| | id = PMID 17005952
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| }}</ref>
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| ! width="22%" | Note
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| |-
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| ! 1
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| | Head
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| | Facial angiofibromas or forehead plaque
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| | Infant – adult
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| |-
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| ! 2
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| | Fingers and toes
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| | Nontraumatic ungual or periungual fibroma
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| | Adolescent – adult
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| |-
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| ! 3
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| | Skin
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| | Hypomelanotic macules
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| | Infant – child
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| | More than three.
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| |-
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| ! 4
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| | Skin
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| | Shagreen patch (connective tissue nevus)
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| | Child
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| |-
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| ! 5
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| | Brain
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| | Cortical tuber
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| | Fetus
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| |-
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| ! 6
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| | Brain
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| | Subependymal nodule
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| | Child – adolescent
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| |-
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| ! 7
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| | Brain
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| | Subependymal giant cell astrocytoma
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| | Child – adolescent
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| |-
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| ! 8
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| | Eyes
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| | Multiple retinal nodular hamartomas
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| | Infant
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| |-
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| ! 9
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| | Heart
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| | Cardiac rhabdomyoma
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| | Fetus
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| | Single or multiple.
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| |-
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| ! 10
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| | Lungs
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| | Lymphangiomyomatosis
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| | Adolescent – adult
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| |-
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| ! 11
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| | Kidneys
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| | Renal angiomyolipoma
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| | Child – adult
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| | '''10''' and '''11''' together count as one major feature.
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| |-
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| ! colspan="5" width="100%" | Minor Features
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| |-
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| ! width="2%" |
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| ! width="12%" | Location
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| ! width="42%" | Sign
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| ! width="44%" colspan="2" | Note
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| |-
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| ! 12
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| | Teeth
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| | Multiple randomly distributed pits in dental enamel
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| | colspan="2" |
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| |-
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| ! 13
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| | Rectum
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| | Hamartomatous rectal polyps
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| | colspan="2" | [[Histology|Histologic]] confirmation is suggested.
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| |-
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| ! 14
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| | Bones
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| | Bone cysts
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| | colspan="2" |
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| |-
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| ! 15
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| | Brain
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| | Cerebral white-matter "migration tracts"
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| | colspan="2" | [[Radiography|Radiographic]] confirmation is sufficient. '''5''' and '''15''' together count as one major feature.
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| |-
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| ! 16
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| | Gums
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| | Gingival fibromas
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| | colspan="2" |
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| |-
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| ! 17
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| | Liver, spleen and other organs
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| | Nonrenal hamartoma
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| | colspan="2" | Histologic confirmation is suggested.
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| |-
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| ! 18
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| | Eyes
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| | Retinal achromic patch
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| | colspan="2" |
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| |-
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| ! 19
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| | Skin
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| | "Confetti" skin lesions
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| | colspan="2" |
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| |-
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| ! 20
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| | Kidneys
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| | Multiple renal cysts
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| | colspan="2" | Histologic confirmation is suggested.
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| |}
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| ===Variability===
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| Individuals with tuberous sclerosis may experience none or all of the clinical signs discussed above. The following table shows the prevalence of some of the clinical signs in individuals diagnosed with tuberous sclerosis.<br style="clear:both;">
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| [[Image:TSC-Frequency-Signs-Childhood.png|550px|thumb|left|The frequency of clinical signs in children with tuberous sclerosis, grouped by age<ref name="TSC-diagnosis">Curatolo (2003), chapter: "Diagnostic Criteria".</ref>]]<br style="clear:both;">
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| The various signs are then marked against the diagnostic criteria to produce a level of diagnostic certainty:
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| *'''Definite''' – Either two major features or one major feature plus two minor features.
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| *'''Probable''' – One major plus one minor feature.
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| *'''Suspect''' – Either one major feature or two or more minor features.
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| ===Symptoms===
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| * Skin problems, such as light patches and thickened skin
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| * [[Seizures]]
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| * [[Behavior problems]]
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| * Learning disabilities - seen in 50% patients ranging from mild to profound,<ref name="memory-deficits">{{cite journal
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| | author = Ridler K, ''et al''
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| | title = Neuroanatomical Correlates of Memory Deficits in Tuberous Sclerosis Complex
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| | journal = Cerebral Cortex
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| | year = 2006
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| | id = PMID 16603714 }}</ref> and studies have reported that between 25% and 61% of affected individuals meet the diagnostic criteria for [[autism]], with an even higher proportion showing features of a broader [[pervasive developmental disorder]].<ref name="autism-prevalence">{{cite journal
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| | author = Harrison JE, Bolton, PF
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| | title = Annotation: Tuberous sclerosis
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| | journal = Journal of Child Psychology and Psychiatry
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| | year = 1997
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| | pages = 603-614
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| | volume = 38
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| | id = PMID 9315970}}</ref>
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| * [[Mental retardation]]
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| * Kidney problems
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| Most of the neurologic manifestations of tuberous sclerosis are due to the effects of hamartia (malformed tissue such as the cortical tubers),[[hamartoma]]s (benign growths such as facial [[angiofibroma]] and subependymal nodules) and, very rarely, cancerous hamartoblastomas on the brain tissue.
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| In infants, the first clue is often the presence of [[seizures]], [[delayed development]] or white patches on the skin. A full clinical diagnostic workup should be undertaken in such situations.<ref name="TSFactSheet">{{cite web
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| | url = http://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm
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| | title = Tuberous Sclerosis Fact Sheet
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| | accessdate = 2006-10-03
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| | date = [[2006-04-11]]
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| | publisher = National Institute of Neurological Disorders and Stroke
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| }}</ref><ref name="TSAclinicalGuidelines">{{cite web
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| | url = http://www.tuberous-sclerosis.org/publications/clinicalguidelinessummary.pdf
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| | title = Summary of Clinical guidelines for the care of patients with Tuberous Sclerosis Complex
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| | accessdate = 2006-10-03
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| | year = 2002
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| | month = April
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| | publisher = Tuberous Sclerosis Association
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| }}</ref>
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| ===Physical Examination ===
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| ====Skin====
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| [http://www.peir.net Images of the nail shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| <div align="left">
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| <gallery heights="175" widths="175">
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| image:Adenoma_sebaceum.jpg|Adenoma sebaceum.
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| image:Subungual fibroma.jpg|[[Tuberous sclerosis]]; Subungual fibroma; Beneath the Left Index Nail
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| image:Periungual fibroma.jpg|[[Tuberous sclerosis]], Periungual Fibroma; Lateral Side of Left Great Toe Nail
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| </gallery>
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| </div>
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| The skin is examined under a [[Wood's lamp]]. The most common skin abnormalities include:
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| * Facial angiofibromas
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| * Ungual or subungual fibromas
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| * Hypomelanic [[macules]] ("ash leaf spots")
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| * Forehead plaques
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| * Shagreen patches
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| * Molluscum fibrosum or skin tags
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| * [[Cafe-au-lait spots]] or flat brown marks
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| * Poliosis
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| ====Head==== | | ==[[Tuberous sclerosis historical perspective|Historical Perspective]]== |
| * Pitted tooth [[enamel]]
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| * Rubbery growths on the tongue or gums
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| ====Eyes==== | | ==[[Tuberous sclerosis classification|Classification]]== |
| * Retinal lesions - astrocytic hamartomas
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| * Non-retinal lesions associated with TSC include
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| ** [[Coloboma]]
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| ** Angiofibromas of the eyelids
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| ** [[Papilledema]] (related to hydrocephalus)
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| ====Heart==== | | ==[[Tuberous sclerosis pathophysiology|Pathophysiology]]== |
| * A heart murmur can be heard due to the obstruction of blood flow by [[rhabdomyomas]].
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| ====Lungs==== | | ==[[Tuberous sclerosis causes|Causes]]== |
| * Coarse rales are heard when lung parenchyma is involved.
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| * Bronchial breathing and bronchophony are heard on auscultation when multiple cysts occur in the lungs.
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| ====Extremities==== | | ==[[Tuberous sclerosis differential diagnosis|Differentiating Any Disease from other Diseases]]== |
| * Rough growths under or around the fingernails and toenails
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| ====Neurologic==== | | ==[[Tuberous sclerosis epidemiology and demographics|Epidemiology and Demographics]]== |
| * Abnormal size of head in children - due to [[hydrocephalus]]
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| * Low IQ
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| * Learning difficulties
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| * Intellectual disability
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| * Troubled communication and social interaction
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| ===Lab tests=== | | ==[[Tuberous sclerosis risk factors|Risk Factors]]== |
| [[Molecular genetic testing]] is commercially available in the United States for the diagnosis of [[tuberous sclerosis]]. Genetic testing identifies mutations only in 75% - 80%. The 15%-20% failure rate is thought to be due to somatic mosaicism. Therefore a negative genetic test does not rule out the diagnosis of tuberous sclerosis. | |
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| ===Imaging=== | | ==[[Tuberous sclerosis screening|Screening]]== |
| ====CT====
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| {| align="center"
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| |+ '''Tuberous sclerosis'''
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| !
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| |-valign="top"
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| | [[Image:TS-LAM.png|thumb|This CT image shows randomly arranged cysts in both lungs. The patient had TSC and a renal AML.]] | |
| | [[Image:bilateralrenalAML.jpg|thumb|140px|This is an image from a contrast-enhanced [[computed tomography]] (CT) scan of the abdomen in another patient with TSC.]]
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| |}
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| ====MRI==== | | ==[[Tuberous sclerosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| The tubers are typically triangular in configuration, with the apex pointed towards the ventricles, and are thought to represent foci of abnormal neuronal migration. The T2 signal abnormalities may subside in adulthood, but will still be visible on histopathological analysis. On [[MR|magnetic resonance imaging]], TSC patients can exhibit other signs consistent with abnormal neuron migration (radial white matter tracts hyperintense on T2WI, heterotopic gray matter).
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| [[Image:tuberoussclerosisbrainFLAIR.png|thumb|center|300px|[[MRI]] of the brain in a patient with TSC.]] | | ==Diagnosis== |
| | | [[Tuberous sclerosis history and symptoms|History and Symptoms]] | [[Tuberous sclerosis physical examination|Physical Examination]] | [[Tuberous sclerosis laboratory findings|Laboratory Findings]] | [[Tuberous sclerosis electrocardiogram|Electrocardiogram]] | [[Tuberous sclerosis chest x ray|Chest X Ray]] | [[Tuberous sclerosis CT|CT]] | [[Tuberous sclerosis MRI|MRI]] | [[Tuberous sclerosis echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Tuberous sclerosis other imaging findings|Other Imaging Findings]] | [[Tuberous sclerosis other diagnostic studies|Other Diagnostic Studies]] |
| ====Echocardiography====
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| * A cardiac rhabdomyoma can be discovered using [[echocardiography]] in approximately 50% of people with TSC.
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| ====Ultrasoud====
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| * Ultrasound abdomen is used to visualize kidney [[angiomyolipomas]] and cysts
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| * Prenatal ultrasound, performed by an [[Obstetric ultrasonography|obstetric sonographer]] specializing in cardiology, can detect a rhabdomyoma after 20 weeks. This rare tumour is a strong indicator of TSC in the child, especially if there is a family history of TSC.
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| ==Treatment== | | ==Treatment== |
| ===Medical therapy===
| | [[Tuberous sclerosis medical therapy|Medical Therapy]] | [[Tuberous sclerosis surgery|Surgery]] | [[Tuberous sclerosis primary prevention|Primary Prevention]] | [[Tuberous sclerosis secondary prevention|Secondary Prevention]] | [[Tuberous sclerosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Tuberous sclerosis future or investigational therapies|Future or Investigational Therapies]] |
| '''Drug therapy''' for some of the manifestations of TSC is currently in the developmental stage.<ref>{{cite journal | pmid = 16868562 | doi=10.1038/sj.ejhg.5201625 | volume=14 | issue=10 | title=Tuberous sclerosis | year=2006 | month=October | author=Yates JR | journal=Eur. J. Hum. Genet. | pages=1065–73}}</ref> For example, a 2008 study found that treatment with [[rapamycin]] rescued learning and memory deficits in a mouse model of tuberous sclerosis.<ref>{{cite journal |journal= Nat Med |year=2008 |title= Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis |author= Ehninger D, Han S, Shilyansky C ''et al.'' |doi=10.1038/nm1788 |pmid=18568033 |laysummary=http://www.sciencedaily.com/releases/2008/06/080622224428.htm |laysource= Science News |laydate=23 June 2008 |volume= 14 |pages= 843–8 |issue= 8 |pmc= 2664098}}</ref> [[Community TSC]] is a distributed computing project to find drugs to treat TSC.{{Citation needed|date=June 2008|laysummary=http://www.childhooddiseases.org/community_tsc.html}}
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| The patients usually have relapse of symptoms in the clinical course. Unless any vital function is affected, life expectancy is good. Majority of patients will require some medications to control symptoms, e.g., anti-epileptics to control seizures.
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| In 2010 [[everolimus]] was approved for the treatment of [[subependymal giant cell astrocytoma]].
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| Other drugs used include:
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| * [[Vigabatrin]]<ref name="pmid19557123">{{cite journal |author=Tsao CY |title=Current trends in the treatment of infantile spasms |journal=Neuropsychiatr Dis Treat |volume=5 |issue= |pages=289–99 |year=2009 |pmid=19557123 |pmc=2695218 |doi= |url=http://www.dovepress.com/articles.php?article_id=3150}}</ref>
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| * [[ACTH]]<ref name="Shorvon2010">{{cite book|author=Simon D. Shorvon|title=Handbook of Epilepsy Treatment|url=http://books.google.com/books?id=ce1YGxllLsgC&pg=PA93|accessdate=11 October 2010|year=2010|publisher=John Wiley and Sons|isbn=978-1-4051-9818-9|pages=93–}}</ref>
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| '''Facial angiofibromas''' is a socially embarrassing rash that starts to appear during childhood and can be removed using [[dermabrasion]] or laser treatment.
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| ===Surgical therapy===
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| '''Ungual''' or '''subungual fibromas''' may need to be surgically removed if they enlarge or cause bleeding.
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| ==References==
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| {{Reflist|2}}
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| ====Support Groups====
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| * United Kingdom: [http://www.tuberous-sclerosis.org/ The Tuberous Sclerosis Association]. Awareness month is October.
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| * United States: [http://www.tsalliance.org/ Tuberous Sclerosis Alliance]. Awareness month is May.
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| * Canada: [http://www.tscst.org/ Tuberous Sclerosis Canada]. Awareness month is May.
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| * Australasia: [http://www.atss.org.au/ Australasian Tuberous Sclerosis Society].
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| * Brazil: [http://www.abet.org.br/entrada.htm Associação Brasileira de Esclerose Tuberosa (''Brazilian Tuberous Sclerosis Association'')] {{pt icon}}
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| * Taiwan: [http://www.ttsc.org.tw Taiwan Tuberous Sclerosis Complex]
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| {{Phakomatoses and other congenital malformations not elsewhere classified}}
| | ==Case Studies== |
| | [[Tuberous sclerosis case study one|Case #1]] |
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| [[Category:Genetic disorders]]
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| [[Category:Disease]]
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| [[Category:Neurology]]
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| [[es:Esclerosis tuberosa]] | | [[Category:Projects]] |
| [[fr:Sclérose tubéreuse de Bourneville]] | | [[Category:Help]] |
| [[ja:結節性硬化症]]
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| [[pl:Stwardnienie guzowate]]
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| [[zh:结节性硬化症]]
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