TS was first observed by von Recklinshausen in 1862, and was named by Bourneville as tuberous sclerosis in 1880; he described it as a "'tuberous sclerosis of the cerebral circumvolutions' for the unique cerebral pathologic changes he found in the brain of a 15 year-old epileptic and mentally handcapped girl" (2). The patient's face was also scarred with lesions, now know as facial angiofibroma (2). By the early 1900's TS was made according to evidence of what is known as the Vogt triad, including seizures, mental retardation, and the facial angiofibroma. It is now known that this triad is not necessarily needed to diagnose TS. The current diagnosis is based upon the following:
Multiple ungual fibroma,
Multiple retinal astrocytomas,
Histologically verified cortical tubers or subependymal nodules (2)
Usually the first evidence of the disease are the skin lesions. They may be mistaken for birthmarks, but skin lesions of tuberous sclerosis include *adenoma sebaceum, **Shagreen patches, periungual fibromata, or ash-leaf hypopigmentation (6). Skin lesions are usually treated by a dermatologist or are surgically removed if they become irritated.
According to the Virtual Hospital, other organ systems are usually also affected by tuberous sclerosis. Other afflictions include rhabdomyomas of the heart, lung afflictions, angiomyolipomas of the kidneys, pancreatic cysts, and skeletal deformations (8). While TS virtually effects the entire person, its most common threat is that on the nervous system. About 80-90% of patients experience a type of epileptic seizure: infantile spasms, tonic-clonic, tonic, akinetic, myoclonic, or atypical (2). Evidence from MRI reveals that patients with severe cerebral disruption have a greater chance of uncontrolled seizures and mental retardation. Most of the mentally handicapped patients are afflicted with epileptic fits, but retardation varies according to the severity of the seizures and the location and size of lesions. About 50% of TS children are mentally retarded to some degree, but studies show that the brain deterioration usually stabilizes (2). Other CNS afflictions in TS patients commonly include: autism, ADD, hyperactivity, aggressiveness, and anxiety disorders.
"Many of the clinical manifestations of TS result from hamartomatous malformations (of fibrous and connective tissue) in affected organs, and abnormal migration plays a major role in neurologic dysfunction" (2). Tuberous sclerosis is described as an autosomal dominant ***phakomatosis trait with a "variable penetrance and about a 50-60% mutation rate" (2). Statistics show that if a parent has the disorder, there is about a 50% chance her child will be afflicted (2). Genetic linkage studies reveal two TS genes the TSC1 on chromosome 9 and TSC2 on chromosome
"Many of the clinical manifestations of TS result from hamartomatous malformations (of fibrous and connective tissue) in affected organs, and abnormal migration plays a major role in neurologic dysfunction" (2). Tuberous sclerosis is described as an autosomal dominant ***phakomatosis trait with a "variable penetrance and about a 50-60% mutation rate" (2). Statistics show that if a parent has the disorder, there is about a 50% chance her child will be afflicted (2). Genetic linkage studies reveal two TS genes the TSC1 on chromosome 9 and TSC2 on chromosome 16. In a genetic study conducted in England, about 40% had TSC1, and 50% had the TSC2 gene (2).
Researchers believe that the protein, Tuberin (which normally supresses tumors in the body) is deficient in TS patients(4). "The mutation found on chromosome 16 produces an A instead of a G and it is believed that then the tuberin protein command to produce is then stopped by the TGA stop code. The theory is that since he does not produce tuberin which is a tumor suppressor causing tumors to then grow"(4).
During the next few years, the genetic mapping for the TS gene on chromosome nine will continue. Most TS patients life spans are not detrimented by the disease, itself, if properly managed. Seizure suppressing medications can prevent brain damaging seizures, organ and skin lesions can be removed if severe, and dermatologists can normally treat minor skin fibromas. Researcher hope that if Tuberin can be replicated in the body, the majority of complications of tuberous sclerosis can be reduced.
Definitions according to (6):
"*Adenoma sebaceum: raised, red papules on the face, mainly about the nose; misnomer: they're really perivascular fibromata
** Shagreen patches: normal-colored plaques on trunk with firmer texture than normal skin
*** Phakomatosis: all autosomal dominant except ataxia-telangiectasia wide range of penetrance and expressivity high rate of sporadic cases (spont. mutation)."
2) National Tuberous Sclerosis Association, An excellent description and history on TS
3)Patient's (Lisa) CT Scan, To view TS's effect on the brain. An incredible homepage of a woman with TS
4) Luke's Tuberous Sclerosis Page, A homepage of a child, Luke, very informative.
5)TS mutation on ninth chromosome, an Image of Luke's DNA test
6)Chorus Hypertext , Medical terms defined, from the Medical College of Wisconsin.
7) CNS Pathology , Pictures of the Brain
8)Virtual Hospital's Resident Case of the Week , Very informative description of TS
9)Ethan's Tuberous Sclerosis Page, An in depth look at TS by a father.
10) NTSA's comprehensive list of TS information on the web,
11)The Virtual Children's Hospital , Definition of TS
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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.