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{{SK}} Tuberous sclerosis complex, TSC, Bourneville disease, Bourneville-Pringle syndrome, epiloia
{{SK}} Tuberous sclerosis complex, TSC, Bourneville disease, Bourneville-Pringle syndrome, epiloia
==Natural History, Complications, Prognosis==
===Natural History===
* Those individuals with mild symptoms generally do well and live long productive lives, while individuals with the more severe form may have serious disabilities.
* However, with appropriate medical care, most individuals with the disorder can look forward to normal life expectancy.<ref name="TSFactSheet"/>
===Complications===
* [[Cardiac failure]] due to [[rhabdomyomas]]
* [[Bronchopneumonia]]
* [[Lymphangiomyomatosis]] of the lung is only a risk for females with AMLs.<ref name="Rakowski2006">{{cite journal
| author = Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA.
| title = Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors.
| journal = Kidney International
| volume =
| issue =
| pages =
| year = 2006
| id = PMID 17003820
}}</ref>
* [[Renal failure]]
* [[Autosomal dominant]] [[polycystic kidney disease]] in 2 % patients.
* [[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
| author = Shepherd C, Gomez M, Lie J, Crowson C
| title = Causes of death in patients with tuberous sclerosis.
| journal = Mayo Clin Proc
| volume = 66
| issue = 8
| pages = 792-6
| year = 1991
| id = PMID 1861550
}}</ref>
* [[Renal cell carcinoma]] is uncommon.
* [[Brain tumor]]
* [[Status epilepticus]]
* Subependymal giant cell astrocytomas (SEGA)
* [[Hydrocephalus]]
===Prognosis===
* 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]].
== Diagnosis ==  
== Diagnosis ==  
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.
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.

Revision as of 17:54, 27 February 2013

Tuberous sclerosis
Earliest illustration, from Rayer's atlas of skin diseases, 1835.

Tuberous sclerosis Microchapters

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Differentiating Tuberous sclerosis from other Diseases

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Physical Examination

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Synonyms and keywords: Tuberous sclerosis complex, TSC, Bourneville disease, Bourneville-Pringle syndrome, epiloia

Diagnosis

There are no pathognomonic clinical 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.

Diagnostic Criteria for Tuberous Sclerosis Complex[1]
Major Features
Location Sign Onset[2] Note
1 Head Facial angiofibromas or forehead plaque Infant – adult
2 Fingers and toes Nontraumatic ungual or periungual fibroma Adolescent – adult
3 Skin Hypomelanotic macules Infant – child More than three.
4 Skin Shagreen patch (connective tissue nevus) Child
5 Brain Cortical tuber Fetus
6 Brain Subependymal nodule Child – adolescent
7 Brain Subependymal giant cell astrocytoma Child – adolescent
8 Eyes Multiple retinal nodular hamartomas Infant
9 Heart Cardiac rhabdomyoma Fetus Single or multiple.
10 Lungs Lymphangiomyomatosis Adolescent – adult
11 Kidneys Renal angiomyolipoma Child – adult 10 and 11 together count as one major feature.
Minor Features
Location Sign Note
12 Teeth Multiple randomly distributed pits in dental enamel
13 Rectum Hamartomatous rectal polyps Histologic confirmation is suggested.
14 Bones Bone cysts
15 Brain Cerebral white-matter "migration tracts" Radiographic confirmation is sufficient. 5 and 15 together count as one major feature.
16 Gums Gingival fibromas
17 Liver, spleen and other organs Nonrenal hamartoma Histologic confirmation is suggested.
18 Eyes Retinal achromic patch
19 Skin "Confetti" skin lesions
20 Kidneys Multiple renal cysts Histologic confirmation is suggested.

Variability

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.

The frequency of clinical signs in children with tuberous sclerosis, grouped by age[3]


The various signs are then marked against the diagnostic criteria to produce a level of diagnostic certainty:

  • Definite – Either two major features or one major feature plus two minor features.
  • Probable – One major plus one minor feature.
  • Suspect – Either one major feature or two or more minor features.

Symptoms

Most of the neurologic manifestations of tuberous sclerosis are due to the effects of hamartia (malformed tissue such as the cortical tubers),hamartomas (benign growths such as facial angiofibroma and subependymal nodules) and, very rarely, cancerous hamartoblastomas on the brain tissue.

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.[6][7]

Physical Examination

Skin

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

The skin is examined under a Wood's lamp. The most common skin abnormalities include:

  • Facial angiofibromas
  • Ungual or subungual fibromas
  • Hypomelanic macules ("ash leaf spots")
  • Forehead plaques
  • Shagreen patches
  • Molluscum fibrosum or skin tags
  • Cafe-au-lait spots or flat brown marks
  • Poliosis

Head

  • Pitted tooth enamel
  • Rubbery growths on the tongue or gums

Eyes

  • Retinal lesions - astrocytic hamartomas
  • Non-retinal lesions associated with TSC include

Heart

  • A heart murmur can be heard due to the obstruction of blood flow by rhabdomyomas.

Lungs

  • Coarse rales are heard when lung parenchyma is involved.
  • Bronchial breathing and bronchophony are heard on auscultation when multiple cysts occur in the lungs.

Extremities

  • Rough growths under or around the fingernails and toenails

Neurologic

  • Abnormal size of head in children - due to hydrocephalus
  • Low IQ
  • Learning difficulties
  • Intellectual disability
  • Troubled communication and social interaction

Lab tests

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.

Imaging

CT

Tuberous sclerosis
This CT image shows randomly arranged cysts in both lungs. The patient had TSC and a renal AML.
This is an image from a contrast-enhanced computed tomography (CT) scan of the abdomen in another patient with TSC.

MRI

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 magnetic resonance imaging, TSC patients can exhibit other signs consistent with abnormal neuron migration (radial white matter tracts hyperintense on T2WI, heterotopic gray matter).

MRI of the brain in a patient with TSC.

Echocardiography

  • A cardiac rhabdomyoma can be discovered using echocardiography in approximately 50% of people with TSC.

Ultrasoud

  • Ultrasound abdomen is used to visualize kidney angiomyolipomas and cysts
  • Prenatal ultrasound, performed by an 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.

Treatment

Medical therapy

Drug therapy for some of the manifestations of TSC is currently in the developmental stage.[8] For example, a 2008 study found that treatment with rapamycin rescued learning and memory deficits in a mouse model of tuberous sclerosis.[9] Community TSC is a distributed computing project to find drugs to treat TSC.[citation needed] 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. In 2010 everolimus was approved for the treatment of subependymal giant cell astrocytoma.

Other drugs used include:

Facial angiofibromas is a socially embarrassing rash that starts to appear during childhood and can be removed using dermabrasion or laser treatment.

Surgical therapy

Ungual or subungual fibromas may need to be surgically removed if they enlarge or cause bleeding.

References

  1. ↑ Roach E, Sparagana S (2004). "Diagnosis of tuberous sclerosis complex". Journal of Child Neurology. 19 (9): 643–9. PMID 15563009.
  2. ↑ Crino P, Nathanson K, Henske E (2006). "The Tuberous Sclerosis Complex". New England Journal of Medicine. 355 (13): 1345–56. PMID 17005952.
  3. ↑ Curatolo (2003), chapter: "Diagnostic Criteria".
  4. ↑ Ridler K; et al. (2006). "Neuroanatomical Correlates of Memory Deficits in Tuberous Sclerosis Complex". Cerebral Cortex. PMID 16603714.
  5. ↑ Harrison JE, Bolton, PF (1997). "Annotation: Tuberous sclerosis". Journal of Child Psychology and Psychiatry. 38: 603–614. PMID 9315970.
  6. ↑ "Tuberous Sclerosis Fact Sheet". National Institute of Neurological Disorders and Stroke. 2006-04-11. Retrieved 2006-10-03. Check date values in: |date= (help)
  7. ↑ "Summary of Clinical guidelines for the care of patients with Tuberous Sclerosis Complex" (PDF). Tuberous Sclerosis Association. 2002. Retrieved 2006-10-03. Unknown parameter |month= ignored (help)
  8. ↑ Yates JR (2006). "Tuberous sclerosis". Eur. J. Hum. Genet. 14 (10): 1065–73. doi:10.1038/sj.ejhg.5201625. PMID 16868562. Unknown parameter |month= ignored (help)
  9. ↑ Ehninger D, Han S, Shilyansky C; et al. (2008). "Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis". Nat Med. 14 (8): 843–8. doi:10.1038/nm1788. PMC 2664098. PMID 18568033. Lay summary – Science News (23 June 2008).
  10. ↑ Tsao CY (2009). "Current trends in the treatment of infantile spasms". Neuropsychiatr Dis Treat. 5: 289–99. PMC 2695218. PMID 19557123.
  11. ↑ Simon D. Shorvon (2010). Handbook of Epilepsy Treatment. John Wiley and Sons. pp. 93–. ISBN 978-1-4051-9818-9. Retrieved 11 October 2010.

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