Download Tuberous Sclerosis info sheet final

Tuberous Sclerosis
Tuberous Sclerosis complex (TSC) is a genetic disorder that causes nonGenetic
Characteristics malignant tumours to form in many different organs, primarily in the
brain, eyes, heart, kidney, skin and lungs. The aspects of TSC that most
strongly impact quality of life are generally associated with the brain:
seizures, developmental delay, intellectual disability and autism, The
incidence and severity of the various aspects of TSC can vary widely
between individuals.
Although some individuals inherit the disorder from a parent with TSC,
most cases occur as sporadic cases due to new, spontaneous mutations in
TSC1 or TSC2. In this situation, neither parent has the disorder or the
faulty gene(s). Instead, a faulty gene first occurs in the affected
individual.
Prevalence
Current estimates place tuberous sclerosis complex affected births at one
in 6,000.
Nearly one million people worldwide are estimated to have TSC.
Prevalence of
ASD in
Tuberous
Sclerosis
Studies show figures of 17–58% of TSC subjects manifesting autism and
0.4–3% of individuals with ASD having TSC.
Equal sex ratio of individuals who have diagnosis of ASD and TSC.
Generally those with TSC who are diagnosed with Autism have a
cognitive impairment and seizures.
According to Bolton et al. (2004) individuals with tuberous sclerosis are
at very high risk of developing an autism spectrum disorder when
temporal lobe tubers are present and associated with temporal lobe
epileptiform discharges and early onset, persistent spasm like seizures.
Causes
TSC is caused by defects, or mutations, on two genes-TSC1 and TSC2.
Only one of the genes needs to be affected for TSC to be present. The
TSC1 gene, discovered in 1997, is on chromosome 9 and produces a
protein called hamartin. The TSC2 gene, discovered in 1993, is on
chromosome 16 and produces the protein tuberin. Scientists believe these
proteins act in a complex as growth suppressors by inhibiting the
activation of a master, evolutionarily conserved kinase called mTOR.
Loss of regulation of mTOR occurs in cells lacking either hamartin or
tuberin, and this leads to abnormal differentiation and development, and
to the generation of enlarged cells, as are seen in TSC brain lesions.
Diagnosis
The diagnosis of TSC is based upon clinical criteria. In many cases the
first clue to recognizing TSC is the presence of seizures or delayed
development. In other cases, the first sign may be white patches on the
Regional Autism Team. Differential Diagnosis information. August 2013.
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skin (hypomelanotic macules) or the identification of cardiac tumor
rhabdomyoma..
Diagnosis of the disorder is based on a careful clinical exam in
combination with computed tomography (CT) or magnetic resonance
imaging (MRI) of the brain, which may show tubers in the brain, and an
ultrasound of the heart, liver, and kidneys, which may show tumors in
those organs.
Shared
features with
ASD.
Social withdrawl, impaired social contact, stereotyped behaviours and
abnormal speech.
Treatment
There is no cure for TSC, although treatment is available for a number of
the symptoms. Rapamycin and related drugs are not yet approved by the
U.S. Food and Drug Administration (FDA) for any purpose in individuals
with TSC. The FDA has approved the drug everolimus (Afinitor®) to
treat subependymal giant cell astrocytomas (SEGA brain tumors) and
angiomyolipoma kidney tumors. Antiepileptic drugs such as vigabatrin
may be used to control seizures and medications may be prescribed for
behavior problems. Intervention programs, including special schooling
and occupational therapy, may benefit individuals with special needs and
developmental issues. Surgery, including dermabrasion and laser
treatment, may be useful for treatment of skin lesions. Because TSC is a
lifelong condition, individuals need to be regularly monitored by a
doctor. Due to the many varied symptoms of TSC, care by a clinician
experienced with the disorder is recommended.
More
information



Tuberous Sclerosis Alliance. [email protected]
Epilepsy foundation.
National Institute of Neurological disorders and stroke
http://www.ninds.nih.gov/disorders/tuberous_sclerosis/
Physical features and natural history:
The natural course of TSC varies from individual to individual, with symptoms
ranging from very mild to quite severe.
In addition to the benign tumours that frequently occur in TSC, other common
symptoms include:
 Seizures,
 Learning disability,
 Behavior problems,
 Skin abnormalities,
 Tumors can grow in nearly any organ, but they most commonly occur in
the brain, kidneys, heart, lungs, and skin.
Useful Research Papers
Regional Autism Team. Differential Diagnosis information. August 2013.
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Bolton, P., Higgins, R., Griffiths, P., Pickles, A. (2004.) Neuroepileptic determinants
of autism spectrum disorders in tuberous sclerosis complex. Journal of Child
Neurology 2004;19:675—679.
Smalley, S. (1998). Journal of Autism and Developmental Disorders. Volume 28,
Issue 5, pp 407-414
.
.
.
Regional Autism Team. Differential Diagnosis information. August 2013.
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