Tuberous Sclerosis Differential Diagnoses

  • Author: David Neal Franz, MD; Chief Editor: Amy Kao, MD   more...
 
Updated: May 8, 2012
 
 

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

David Neal Franz, MD  Professor of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center

David Neal Franz, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Medical Association, Child Neurology Society, Children's Oncology Group, and Ohio State Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Cameron W Thomas, MD  Assistant Professor of Pediatrics and Neurology, Department of Neurology, Cincinnati Children's Hospital Medical Center

Cameron W Thomas, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert J Baumann, MD  Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Kenneth J Mack, MD, PhD  Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience

Disclosure: Nothing to disclose.

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Amy Kao, MD  Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tracy A Glauser, MD to the development and writing of this article.

References

  1. Van Slegtenhorst M, Nellist M, Nagelkerken B. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 7(6):1053-7. [Medline].

  2. Nobukini T, Thomas G. The mTOR/S6K signalling pathway: the role of the TSC1/2 tumour suppressor complex and the proto-oncogene Rheb. Novartis Found Symp. 2004;262:148-54; discussion 154-9, 265-8. [Medline].

  3. Dabora SL, Jozwiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. Jan 2001;68(1):64-80. [Medline].

  4. Gates J, Jordan JE. Tuberous sclerosis in old age. South Med J. Aug 1978;71(8):974-6. [Medline].

  5. Sampson JR, Attwood D, al Mughery AS, Reid JS. Pitted enamel hypoplasia in tuberous sclerosis. Clin Genet. Jul 1992;42(1):50-2. [Medline].

  6. Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. Oct 24 1996;335(17):1275-80. [Medline].

  7. Flanagan N, O'Connor WJ, McCartan B, et al. Developmental enamel defects in tuberous sclerosis: a clinical genetic marker?. J Med Genet. Aug 1997;34(8):637-9. [Medline].

  8. Beltramello A, Puppini G, Bricolo A, et al. Does the tuberous sclerosis complex include intracranial aneurysms? A case report with a review of the literature. Pediatr Radiol. Mar 1999;29(3):206-11. [Medline].

  9. Goodman M, Lamm SH, Engel A, et al. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. Feb 1997;12(2):85-90. [Medline].

  10. Takanashi J, Sugita K, Fujii K, Niimi H. MR evaluation of tuberous sclerosis: increased sensitivity with fluid- attenuated inversion recovery and relation to severity of seizures and mental retardation. AJNR Am J Neuroradiol. Oct 1995;16(9):1923-8. [Medline].

  11. Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. Jan 10 2008;358(2):140-51. [Medline].

  12. Dabora SL, Franz DN, Ashwal S, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS One. 2011;6(9):e23379. [Medline].

  13. Franz, DN, Leonard, J, Tudor, C. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Annals of Neurology. March 2006;59(3):490-498. [Medline].

  14. Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. Nov 4 2010;363(19):1801-11. [Medline].

  15. DeKlotz CM, Ogram AE, Singh S, Dronavalli S, MacGregor JL. Dramatic improvement of facial angiofibromas in tuberous sclerosis with topical rapamycin: optimizing a treatment protocol. Arch Dermatol. Sep 2011;147(9):1116-7. [Medline].

  16. Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol. Feb 1999;14(2):71-4. [Medline].

  17. Camposano SE, Major P, Halpern E, Thiele EA. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia. Jul 2008;49(7):1186-91. [Medline].

  18. Curatolo P, Verdecchia M, Bombardieri R. Vigabatrin for tuberous sclerosis complex. Brain Dev. Nov 2001;23(7):649-53. [Medline].

  19. Parisi P, Bombardieri R, Curatolo P. Current role of vigabatrin in infantile spasms. Eur J Paediatr Neurol. Nov 2007;11(6):331-6. [Medline].

  20. Willmore LJ, Abelson MB, Ben-Menachem E, Pellock JM, Shields WD. Vigabatrin: 2008 update. Epilepsia. Feb 2009;50(2):163-73. [Medline].

  21. Glauser TA. Topiramate. Epilepsia. 1999;40 Suppl 5:S71-80. [Medline].

  22. Franz DN, Tudor C, Leonard J, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. Jul 2001;42(7):935-40. [Medline].

  23. Avellino AM, Berger MS, Rostomily RC, et al. Surgical management and seizure outcome in patients with tuberous sclerosis. J Neurosurg. Sep 1997;87(3):391-6. [Medline].

  24. Levine NB, Collins J, Franz DN, Crone KR. Gradual formation of an operative corridor by balloon dilation for resection of subependymal giant cell astrocytomas in children with tuberous sclerosis: specialized minimal access technique of balloon dilation. Minim Invasive Neurosurg. Oct 2006;49(5):317-20. [Medline].

  25. Asano E, Chugani DC, Muzik O, et al. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. Oct 9 2001;57(7):1269-77. [Medline].

  26. Asano E, Chugani DC, Muzik O, et al. Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex. Neurology. May 23 2000;54(10):1976-84. [Medline].

  27. Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet. Feb 8 1997;349(9049):392-5. [Medline].

  28. Bowen J, Beasley SW. Rare pulmonary manifestations of tuberous sclerosis in children. Pediatr Pulmonol. Feb 1997;23(2):114-6. [Medline].

  29. Bruni O, Cortesi F, Giannotti F, Curatolo P. Sleep disorders in tuberous sclerosis: a polysomnographic study. Brain Dev. Jan-Feb 1995;17(1):52-6. [Medline].

  30. Christophe C, Sekhara T, Rypens F, et al. MRI spectrum of cortical malformations in tuberous sclerosis complex. Brain Dev. Dec 2000;22(8):487-93. [Medline].

  31. Chugani DC, Chugani HT, Muzik O, et al. Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography. Ann Neurol. Dec 1998;44(6):858-66. [Medline].

  32. Crino, PB, Nathanson, KL, Henske, EP. The tuberous sclerosis complex. New England Journal of Medicine. Sep 28 2006;355(13):1345-56. [Medline].

  33. El-Hashemite N, Zhang H, Walker V, et al. Perturbed IFN-gamma-Jak-signal transducers and activators of transcription signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin-IFN-gamma treatment. Cancer Res. May 15 2004;64(10):3436-43. [Medline].

  34. Enbergs A, Borggrefe M, Kurlemann G, et al. Ventricular tachycardia caused by cardiac rhabdomyoma in a young adult with tuberous sclerosis. Am Heart J. Dec 1996;132(6):1263-5. [Medline].

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

  36. Franz DN, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. Aug 15 2001;164(4):661-8. [Medline].

  37. Harding B, Copp AJ. Malformations: tuberous sclerosis. In: Greenfield's Neuropathology. 6th ed. Arnold Edward;1997:497-502.

  38. Harrison JE, Bolton PF. Annotation: tuberous sclerosis. J Child Psychol Psychiatry. Sep 1997;38(6):603-14. [Medline].

  39. Henske EP, Wessner LL, Golden J, et al. Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol. Dec 1997;151(6):1639-47. [Medline].

  40. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. Aug 1995;26(2):516-20. [Medline].

  41. Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. May 2000;57(5):662-5. [Medline].

  42. Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev. Mar 2005;69(1):79-100. [Medline].

  43. Jost CJ, Gloviczki P, Edwards WD, et al. Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature. J Vasc Surg. Mar 2001;33(3):639-42. [Medline].

  44. Jozwiak S, Pedich M, Rajszys P, Michalowicz R. Incidence of hepatic hamartomas in tuberous sclerosis. Arch Dis Child. Nov 1992;67(11):1363-5. [Medline].

  45. Kandt RS, Haines JL, Smith M, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet. Sep 1992;2(1):37-41. [Medline].

  46. Kenerson H, Dundon TA, Yeung RS. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res. Jan 2005;57(1):67-75. [Medline].

  47. Koprowski C, Rorke LB. Spinal cord lesions in tuberous sclerosis. Pediatr Pathol. Oct-Dec 1983;1(4):474-80. [Medline].

  48. Langkau N, Martin N, Brandt R. TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios. Eur J Pediatr. Jul 2002;161(7):393-402. [Medline].

  49. Louis DN, Scheithauer BW, Budka H. Meningiomas. In: Pathology and Genetics of Tumours of the Nervous System. London: Oxford University Press;2000:176-84.

  50. Maeda M, Tartaro A, Matsuda T, Ishii Y. Cortical and subcortical tubers in tuberous sclerosis and FLAIR sequence. J Comput Assist Tomogr. Jul-Aug 1995;19(4):660-1. [Medline].

  51. Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development. Cancer Invest. 2004;22(4):588-603. [Medline].

  52. Miller SP, Tasch T, Sylvain M, et al. Tuberous sclerosis complex and neonatal seizures. J Child Neurol. Dec 1998;13(12):619-23. [Medline].

  53. Pui MH, Kong HL, Choo HF. Bone changes in tuberous sclerosis mimicking metastases. Australas Radiol. Feb 1996;40(1):77-9. [Medline].

  54. 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].

  55. 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].

  56. Sener N. Tuberous sclerosis: diffusion MRI findings in the brain. Eur Radiol. Jan 2002;12(1):138-43. [Medline].

  57. Seri S, Cerquiglini A, Pisani F, et al. Frontal lobe epilepsy associated with tuberous sclerosis: electroencephalographic-magnetic resonance image fusioning. J Child Neurol. Jan 1998;13(1):33-8. [Medline].

  58. Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment. AJNR Am J Neuroradiol. Jan 1995;16(1):149-55. [Medline].

  59. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. Feb 1996;38(2):146-55. [Medline].

  60. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. Mar 1993;68(3):367-70. [Medline].

  61. Weber AM, Egelhoff JC, McKellop JM, Franz DN. Autism and the cerebellum: evidence from tuberous sclerosis. J Autism Dev Disord. Dec 2000;30(6):511-7. [Medline].

 
Previous
Next
 
Enhancing subependymal nodules, including a probable giant cell astrocytoma in the region of the foramen of Monro. Subependymal nodules may increase in size over time from one scan to the next, and then stabilize. This lesion had not changed with serial imaging over 2 years. The patient remains asymptomatic and is monitored closely for any deterioration.
Hydrocephalus from a subependymal giant cell astrocytoma in a patient with tuberous sclerosis. The patient presented with acute blindness and ataxia.
Facial angiofibromas in a young man with tuberous sclerosis complex.
Dysplastic periungual fibroma involving the great toe in a patient with tuberous sclerosis.
Gingival fibromas (see arrows) in a patient with tuberous sclerosis. A stain outlines dental pits and craters. Gingival hyperplasia from other causes (eg, phenytoin use) is more diffuse and usually not nodular/focal in nature.
Typical ash leaf macules; the reddish, nodular area at the upper lumbar area is a shagreen patch.
Atrial rhabdomyoma as seen on cardiac CT scan in a patient with tuberous sclerosis.
Nonobstructive ventricular rhabdomyomas in a patient with tuberous sclerosis.
Ventricular rhabdomyomas may diffusely infiltrate the myocardium, as in this patient with tuberous sclerosis. The patient presented with cardiac failure and hydrops at birth. After a period of intensive supportive care and inotropic therapy, she now has essentially normal cardiac function and is on no medications.
Multifocal pulmonary cysts characteristic of lymphangiomyomatosis. As many as 40% of women with tuberous sclerosis have pulmonary cysts on chest CT scan.
Massive bilateral angiomyolipomas in a woman with tuberous sclerosis. She also has lymphangiomyomatosis.
Pre-embolization angiography of the patient with angiomyolipomas shown the previous image. Dysplastic arterial vessels are demonstrated.
Vessels to the angiomyolipoma shown in the previous image have been occluded with coils. This should produce regression of the lesion and prevention of hemorrhage. Functional intervening renal parenchyma is preserved.
Enamel pitting in tuberous sclerosis. Pinpoint size pitting (A) and crater size pitting (B) are visible. Red dye is used to enhance recognition.
Basilar artery aneurysm in a 2-year-old girl with tuberous sclerosis. The arrow shows the anterior aspect of the aneurysm where it abuts the clivus. The lesion was not present on MRI performed 11 months earlier.
This presumed tuber was first noted in the left frontal region. It expanded in size, affecting adjacent structures across the midline and resulting in calcifications still evident in the right frontal region. The tuber then spontaneously involuted. About 20% of tubers may show changes in imaging characteristics over time, requiring close imaging follow-up. This patient remained asymptomatic from the mass effect, and his seizures resolved as the lesion involuted.
This father and all 3 children have tuberous sclerosis complex. The children are now grown up and of normal intelligence, including the young lady at left who is cushingoid from therapy with adrenocorticotropic hormone for infantile spasms.
The child whose CT scan is shown presented with medically intractable epilepsy thought to be due to partial hemimegalencephaly. She became seizure free after partial hemispherectomy. Pathology was consistent with a cortical tuber. She was subsequently found to have multiple ash leaf macules and diagnosed with tuberous sclerosis.
Multiple tubers in a child with tuberous sclerosis, normal intelligence, and well-controlled seizures. High tuber count does not invariably mean poor neurological outcome.
All tubers are not equal. This child has a smaller number of tubers than the patient shown in the previous image, but the tubers are larger in size. She too has normal intelligence and is seizure free on medication.
Mammalian target of rapamycin (mTOR) activates the protein S6 kinase, which enhances cell growth and protein synthesis. It, in turn, is regulated by multiple factors, including insulin, amino acids, the drugs rapamycin and its congeners (eg, RAD001), and the TSC gene products via the GTPase-activating protein Rheb.
Subependymal giant cell astrocytoma prior to stereotactic insertion of balloon catheter as seen on T2-weighted MRI.
Modified angioplasty catheter used in creation of surgical tract for astrocytoma resection.
Catheter placed in proximity to lesion, balloon inflated.
Postoperative T2-weighted MRI in a patient with subependymal giant cell astrocytoma showing gross total resection of giant cell astrocytoma with minimal disruption of overlying cortex.
Mean reduction in simple and complex partial seizures in patients with tuberous sclerosis complex (TSC) who were treated with vagus nerve stimulator at the author's institution at 6 and 12 months. Overall reduction in secondarily generalized seizures was 22% at 12 months (N = 17; 10 boys, 7 girls, aged 3-12 y).
Regression of a giant cell astrocytoma after approximately 15 months oral rapamycin therapy in a 4-year-old patient with tuberous sclerosis.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
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.