eMedicine Specialties > Dermatology > Pediatric Diseases

Tuberous Sclerosis: Differential Diagnoses & Workup

Author: Rabindranath Nambi, MD, DD, DipNB, Consulting Staff, Department of Dermatology, Dudley Group of Hospitals, UK
Contributor Information and Disclosures

Updated: Jan 11, 2010

Differential Diagnoses

Acne Vulgaris
Connective Tissue Nevus
Nevus Anemicus
Vitiligo

Other Problems to Be Considered

Angiofibromas (differentiate from acne vulgaris by telangiectasia, absence of comedones and pustules, and a relatively asymptomatic nature)
Shagreen patch (must be differentiated from connective tissue nevi)
Hypopigmented spots (may need to be differentiated from nevus anemicus, nevus achromicus, and early vitiligo)

Workup

Imaging Studies

  • Evaluation of newly diagnosed tuberous sclerosis patients should include a personal and family history and a clinical examination, including funduscopy, cranial imaging (eg, MRI, nonenhanced CT scanning), renal ultrasonography, and echocardiography in infants.
    • Computed cranial tomography scanning and MRI are performed not only in suspect cases but also in patients whose diagnosis is obvious. Do not use scan results to predict the neurologic outcome of an individual patient. New MRI techniques such as FLAIR (fluid attenuated inversion recovery) help identify small tubers, which may not be detected with other imaging techniques.16
    • If tubers are present, serial imaging scans are essential to evaluate for growth of the tumor.
    • EEG is useful when the initial presentation includes epileptic seizures. EEG is not required in children who do not have epilepsy.
    • Renal ultrasonography is used to evaluate children and older patients in particular for renal tumors.
    • ECG is a baseline study essential to detect any cardiac arrhythmias. Wolff-Parkinson-White syndrome seems to be the most common arrhythmia in patients with tuberous sclerosis complex (TSC).
    • Echocardiography is recommended for patients of any age with symptoms of cardio rhabdomyoma. Because most symptoms occur in neonates, older children do not need to have an echocardiogram, unless it is to confirm a previous dubious diagnosis.
    • Neurodevelopmental testing as age-appropriate screening for behavioral and neurodevelopmental dysfunction at the time of diagnosis is essential. Periodically reassess children with abnormal test results. Newly diagnosed adults with normal social and cognitive function (as demonstrated by educational and career achievements) may not require formal testing. Frequent assessment is probably not warranted in such individuals.
    • Recently, consensus guidelines have been published to help in the assessment of cognitive and behavioral problems in persons with tuberous sclerosis complex. Refer to the Tuberous Sclerosis Association for the guidelines.
    • Molecular diagnosis using DNA-based testing is not yet routinely available but in the future could be developed and would help to identify patients at increased or decreased risk for particular complications.
  • Ongoing evaluation
    • Annual or at least biannual MRI can be performed until age 21 years. At that point, any single tumors identified may need closer monitoring.
    • The frequency of EEG depends upon the clinical features and the treatment response of epilepsy. Consider EEG in the evaluation of a patient with unexplained decline of behavioral or cognitive function, in whom epileptic seizures are suspected.
    • Neurodevelopmental testing should take into account various features of tuberous sclerosis complex, including mental retardation, which is the most common, and other features, which are learning disabilities, autism, and attentional deficit. Repeat assessment around the time that a child enters school and then reassess periodically in response to educational and behavioral concerns.
    • Renal ultrasonography is recommended annually. Patients who have large renal lesions or lesions that have grown substantially should have more frequent follow-up examinations.
    • ECG is indicated in persons with arrhythmias or unexplained loss of consciousness. Repeat echocardiography is not required in asymptomatic patients. Any suggestion of cardiac dysfunction may merit investigations.
    • Pulmonary function testing is reserved for patients with pulmonary dysfunction and may be performed annually. Women should undergo chest CT scanning at least once on reaching adulthood.
  • Evaluation of family members: In a family with only one child affected, evaluation of parents is more important than siblings or relatives.
    • Cranial CT scanning is more likely to detect lesions of tuberous sclerosis as a screening tool; MRI often detects lesions that are not as specific to tuberous sclerosis complex. MRI is the first choice; however, if the scan results are negative and the diagnosis is uncertain, then CT scanning may be performed.
    • Renal lesions occur in about 80% of patients, making renal ultrasonography an important screening test.
    • Echocardiography is not recommended unless compelling cardiac symptoms persuade otherwise because cardiac rhabdomyomas commonly disappear by adulthood.
    • Although molecular diagnosis is not yet commercially available, identifying some patients with tuberous sclerosis complex who do not fulfill clinical diagnostic criteria should soon be feasible.

Histologic Findings

Angiofibromas show atrophic sebaceous glands with dermal fibrosis and dilation of some of the capillaries. The fibrosis occasionally has a glial appearance because of the large size and stellate shape of the fibroblasts. Elastic tissue is absent in the angiofibromas.

The ungual fibromas show mainly fibrosis, rarely capillary dilation.

The shagreen patches show increased dense sclerotic mass of broad collagenous bundles. Normal collagen bundles may sometimes be arranged in an interwoven pattern. The elastic tissue is reduced.

The hypopigmented ash-leaf macule shows normal melanocyte numbers with decreased pigmentation. Electron microscopy shows smaller melanosomes with defective melanization.

More on Tuberous Sclerosis

Overview: Tuberous Sclerosis
Differential Diagnoses & Workup: Tuberous Sclerosis
Treatment & Medication: Tuberous Sclerosis
Follow-up: Tuberous Sclerosis
References
[ CLOSE WINDOW ]

References

  1. Povey S, Burley MW, Attwood J, et al. Two loci for tuberous sclerosis: one on 9q34 and one on 16p13. Ann Hum Genet. May 1994;58:107-27. [Medline].

  2. Astrinidis A, Senapedis W, Henske EP. Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner. Hum Mol Genet. Jan 15 2006;15(2):287-97. [Medline].

  3. Ellisen LW. Growth control under stress: mTOR regulation through the REDD1-TSC pathway. Cell Cycle. Nov 2005;4(11):1500-02. [Medline].

  4. Karbowniczek M, Henske EP. The role of tuberin in cellular differentiation: are B-Raf and MAPK involved?. Ann N Y Acad Sci. Nov 2005;1059:168-73. [Medline].

  5. van Slegtenhorst M, Nellist M, Nagelkerken B, et al. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. Jun 1998;7(6):1053-7. [Medline].

  6. Wand O, Blum S, Shachar E, et al. Tuberous sclerosis in a military pilot. Aviat Space Environ Med. Jul 2009;80(7):657-9. [Medline].

  7. Roach ES, DiMario FJ, Kandt RS, Northrup H. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. Jun 1999;14(6):401-7. [Medline].

  8. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. Dec 1998;13(12):624-8. [Medline].

  9. Prabhu S, Mahesh KP. Tuberous sclerosis with oral angiofibroma: Case report. Br J Oral Maxillofac Surg. Jul 27 2009;[Medline].

  10. Cross JH. Neurocutaneous syndromes and epilepsy-issues in diagnosis and management. Epilepsia. 2005;46 Suppl 10:17-23. [Medline].

  11. Quigg M, Miller JQ. Clinical findings of the phakomatoses: tuberous sclerosis. Neurology. Nov 22 2005;65(10):E22-3. [Medline].

  12. Williams JM, Racadio JM, Johnson ND, Donnelly LF, Bissler JJ. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis. Jan 2006;47(1):95-102. [Medline].

  13. [Guideline] Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. May 25 2004;62(10):1668-81. [Medline].

  14. [Guideline] Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia. Jun 2003;44(6):741-51. [Medline].

  15. [Guideline] Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. Feb 25 2003;60(4):538-47. [Medline].

  16. Altman NR, Purser RK, Post MJ. Tuberous sclerosis: characteristics at CT and MR imaging. Radiology. May 1988;167(2):527-32. [Medline].

  17. Jozwiak J, Jozwiak S, Oldak M. Molecular activity of sirolimus and its possible application in tuberous sclerosis treatment. Med Res Rev. Mar 2006;26(2):160-80. [Medline].

  18. Tuberous Sclerosis Association. Clinical guidelines for the care of patients with Tuberous Sclerosis Complex. Available at: http://www.tuberous-sclerosis.org. England: Birmingham; April, 2002.

  19. Flinter FA, Neville BG. Examining the parents of children with tuberous sclerosis. Lancet. Nov 15 1986;2(8516):1167. [Medline].

  20. Franz DN. Diagnosis and management of tuberous sclerosis complex. Semin Pediatr Neurol. Dec 1998;5(4):253-68. [Medline].

  21. Greenwald MJ, Paller AS. Ocular and dermatologic manifestation of neurocutaneous syndromes. Dermatol Clin. Jul 1992;10(3):623-39. [Medline].

  22. Kwiatkowski DJ, Short MP. Tuberous sclerosis. Arch Dermatol. Mar 1994;130(3):348-54. [Medline].

  23. Roach ES, Delgado MR. Tuberous sclerosis. Dermatol Clin. Jan 1995;13(1):151-61. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

tuberous sclerosis, epiloia, Bourneville disease, tuberous sclerosis complex, TSC

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Rabindranath Nambi, MD, DD, DipNB, Consulting Staff, Department of Dermatology, Dudley Group of Hospitals, UK
Disclosure: Nothing to disclose.

Medical Editor

Eleanor E Sahn, MD, Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina
Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.