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tuberous sclerosis (Bourneville disease, epiloia)

Inherited disease of mesodermal origin. Pathology: - hamartomas - lymphangioleiomyomatosis (females) [4] - angiofibrosis - especially affects the brain, kidneys, heart, & skin - renal angiomyolipoma in 70-80% - renal cysts [4] - renal cell carcinoma - functional impairment of the tuberin-hamartin complex - cardiovascular manifestations a) rhabdomyoma b) cardiomyopathy Genetics: 1) autosomal dominant (25%) 2) sporadic 3) mutations in TSC1, TSC2 [7] Clinical manifestations: 1) epilepsy (80%) 2) mental retardation (60%) 3) congenital tumors - brain neoplasms [4] 4) malformations of the brain, skin & viscera 5) skin manifestations: a) hypopigmented macules (ash leaf spot) b) facial angiofibroma (adenoma sebaceum is misnomer) c) subungual or periungual fibromas d) shagreen patch (connective tissue nevus) e) fibrous plaques of the forehead 6) visual impairment 7) developmental delay [4] 8) autism [4] * images [6,7,8] Diagnostic criteria: 1) major features - facial angiofibromas or forehead plaque - nontraumatic ungual, periungual fibroma or subungual papules - ash leaf spots, hypomelanotic macules (3 or more) - Shagreen patch (connective tissue nevus) - multiple retinal nodular hamartomas - cortical tubers & seizures - subependymal nodule - subependymal giant cell astrocytoma - cardiac rhabdomyoma, single or multiple - lymphangiomyomatosis (females) - renal angiomyolipoma 2) minor features - multiple, randomly distributed pits in dental enamel - hamartomatous rectal polyps - bone cysts - cerebral white matter radial migration lines - gigival fibromas - nonrenal hamartoma - retinal achromic patch - 'confetti' skin lesions - multiple renal cysts 3) definite tuberous sclerosis complex - either 2 major features or 1 major & 2 minor features 4) probable tuberous sclerosis complex - 1 major & 1 minor feature 5) possible - 1 major feature or 2 or more minor features Radiology: - computed tomography (CT) - magnetic resonance imaging (MRI) * images [6] Complications: - kidney neoplasm - renal cell carcinoma - renal angiomyolipoma (a major feature, see Diagnostic criteria) [4] - multiple renal cysts (a minor feature, see Diagnostic criteria) [4] - pain & hemorrhage from renal angiomyolipomas > 4 cm - hemorrhage of renal angiomyolipomas is the most common cause of renal failure & death [4] - premature death from disease-related causes Management: - rapamycin may reduce size &/or number of renal angiomyolipomas - surgery or arterial embolization of renal angiomyolipomas [4] - topical rapamycin 1% QD for facial angiofibromas [9] Notes: - lymphangioleiomyomatosis is an uncommon progressive form in women of child-bearing age which involves the lungs.

Related

lymphangioleiomyomatosis

Specific

tuberous sclerosis 1 tuberous sclerosis 2 tuberous sclerosis 3 tuberous sclerosis 4

General

hereditary neoplastic syndrome; cancer susceptibility syndrome

Properties

ASSOCIATED-NEOPLASM[S]: astrocytoma ependymoma Wilm's tumor rhabdomyoma :SITE heart angiomyolipoma :SITE kidney hamartoma

Database Correlations

OMIM 191100

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 175, 756-57
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 296-97, 1038
  3. Au KS, Williams AT, Gambello MJ, Northrup H. Molecular genetic basis of tuberous sclerosis complex: from bench to bedside. J Child Neurol. 2004 Sep;19(9):699-709. Review. PMID: 15563017
  4. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021.
  5. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008 Aug 23;372(9639):657-68 PMID: 18722871
  6. Franz DN, Kao A Medscape: Tuberous Sclerosis http://emedicine.medscape.com/article/1177711-overview
  7. Schwartz RA, Rohena LO Medscape: Genetics of Tuberous Sclerosis http://emedicine.medscape.com/article/951002-overview
  8. DermNet NZ. Tuberous sclerosis (images) http://www.dermnetnz.org/systemic/tuberous-sclerosis.html
  9. Koenig MK, Bell CS, Hebert AA et al Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex. The TREATMENT Randomized Clinical Trial. JAMA Dermatol. Published online May 23, 2018. PMID: 29800048 https://jamanetwork.com/journals/jamadermatology/fullarticle/2682034
  10. National Institute of Neurological Disorders and Stroke (NINDS) - NINDS Tuberous Sclerosis Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Tuberous-sclerosis-Information-Page - NINDS Tuberous Sclerosis Fact Sheet https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Tuberous-Sclerosis-Fact-Sheet