Tuberous Sclerosis

  • TSC is now known to be an Autosomal dominant disorder affecting cellular differentiation, proliferation, and migration early in development, resulting in a variety of hamartomatous lesions that may affect virtually every organ system of the body.
  • TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively.
  • Diagnostic triad of Tuberous sclerosis includes epilepsy, mental retardation and adenoma sebaceum (facial angiofibroma).
Diagnostic Criteria for Tuberous Sclerosis Complex
Major Criteria
Location Sign Onset Note
1 Head Facial angiofibromas or fibrous cephalic plaque Infant – adult At least three
2 Fingers and toes Nontraumatic ungual or periungual fibroma Adolescent – adult At least two
3 Skin Hypomelanotic macules Infant – child At least three, at least 5 mm in diameter.
4 Skin Shagreen patch (connective tissue nevus) Child
5 Brain Cortical dysplasias (includes tubers
and cerebral white matter radial migration lines)
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 Lymphangioleiomyomatosis Adolescent – adult
11 Kidneys Renal angiomyolipoma Child – adult At least two. Together, 10and 11 count as one major feature.
Minor Criteria
Sign Note
12 Teeth At least three randomly distributed pits in dental enamel
13 Skin "Confetti" skin lesions, 1–2 mm hypomelanotic papules
14 Gums Intraoral fibromas
15 Liver, spleen and other organs Nonrenal hamartoma Histologic confirmation is suggested.
16 Eyes Retinal achromic patch
17 Kidneys Multiple renal cysts Histologic confirmation is suggested.
Exam Question
  • Type of inheritance in Tuberous sclerosis is Autosomal Dominant.
  • Color of tuberous sclerosis lesions on wood lamp examination is Blue-white.
  • Giant cell astrocytoma,Subependymal nodule ,White matter lesion ,Shagreen patch,Depigmented Naevi ,Tubers,Renal Cortical Cyst,Pulmonary lymphangioleiomyomatosis may be seen in Tuberous Sclerosis.
  • Ependymoma is not seen in Tuberous Sclerosis.
  • Tuberous Sclerosis presents with Vogt's triad of epilepsy, low intelligence/mental retardation/ delayed mile stones and adenoma sebaceum (arjgiofibroma of face)(Acronym-Epiloia) Tumor which may be associated with tuberous sclerosis are Renal angiomyoma,Subependymal giant cell astrocytoma,Rhabdomyoma heart.
  • Drug of choice for infantile spasms in a patient with tuberous scleosis is Vigabatrin.
  • A couple has two children affected with tuberous selerosis. On detailed clinical and laboratory evaluation (including molecular studies) both parents are normal. Germline mosaicism explains the two affected children in this family .
  • Asch leaf spot is the earliest feature of Tuberous sclerosis.
  • Koenen's periungual fibromas are associated with Tuberous Sclerosis.
  • Differential diagnosis of congenital disorders of pigmentation includes Tuberous Sclerosis along with Waardenburg syndromes types 1-4 ,Tietz syndrome ,Piebaldism ,Woolf's syndrome ,Generalized vitiligo ,Segmental vitiligo ,Vogt-Koyanagi-Harada syndrome ,Chemical leukoderma Tuberous sclerosis ,Ziprkowski-Margolis syndrome (X-linked albinism-deafness syndrome). 
  • Most probable diagnosis in a child with seizures, oval hypo-pigmented macules on the trunk, and sub-normal IQ is Tuberous sclerosis.
  • Honey comb appearance on X-ray may be seen in Tuberous Sclerosis.
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