Tuberous sclerosis (TS) is a hereditary neurological
condition that affects all ages. The name arises from the potato
stem-shaped growths that occur in the brain, also known as tubers.
These growths often involve overgrowth of nerves or the connective
tissue within them, which is described by the term sclerosis.
Tuberous sclerosis is also known by the names
tuberous sclerosis complex and Bourneville's disease. Neurological
symptoms may include tubers and other non-cancerous growths in the
brain, cancerous brain tumors, seizures, and intellectual disability
or developmental delay.
is seen in about 25 to 50% of people with Tuberous sclerosis, and
this is felt to have a major influence on an individual's daily
functioning. Parents of children with Tuberous sclerosis often raise
concerns about autism or autistic-type
characteristics, because this has a significant impact on routine
activities like attending school. Though scientific studies have
been done to find exact neurological causes for autism in Tuberous
sclerosis, none has provided consistent results.
Nearly everyone with Tuberous sclerosis has some
symptoms affecting their skin. These include light-colored patches
called ash-leaf spots, acne-type growths on the face, nail beds,
and the body, and shagreen patches. Other common symptoms of Tuberous
sclerosis are kidney cysts, kidney growths, and heart tumors that
may develop at a very young age or even before birth.
Demographics of Tuberous sclerosis
According to the National Institute of Neurological
Disorders and Stroke (NINDS),Tuberous sclerosis affects about 1
in 6,000 newborns. As many as 25,000 to 45,000 people in the United
States and 1-2 million people worldwide have the disorder. Its true
incidence may be higher because mildly affected individuals may
not come to medical attention. Tuberous sclerosis has been reported
in all ethnic groups and races with equal frequency. Two genes for
Tuberous sclerosis have been identified, and males and females are
equally affected with the condition. About one third of people with
Tuberous sclerosis have an affected parent as well.
Causes and symptoms of Tuberous sclerosis
Always known to be hereditary, mutations in two
different genes are now known to cause Tuberous sclerosis. These
genes are TSC1 and TSC2, and were discovered in 1993 and 1997 on
chromosomes 16 and 9 respectively. Tuberous sclerosis is inherited
in an autosomal dominant manner, meaning that an affected individual
has a 50/50 chance to pass a disease-causing mutation to his or
her children, regardless of their gender. As a result, strong family
histories of Tuberous sclerosis are common.
TSC1 and TSC2 normally code for specific proteins,
hamartin and tuberin, which are felt to be necessary for neurological
functioning. Reduced amounts of these proteins in the brains of
people with Tuberous sclerosis may contribute to the neurological
complications associated with the condition.
The most common neurological symptoms in Tuberous
sclerosis include seizures,
learning and behavioral problems, and hydrocephalus. Seizures affect
about 85% of people at some point in their lives. They can begin
in very early childhood as infantile spasms, sometimes with hypsarrhythmia.
The presence of these spasms at an early age often means more significant
learning problems and more significant epilepsy
Learning problems are not a certainty with Tuberous
sclerosis; about 50% of people with the condition are known to have
developmental delay or intellectual disability. People with Tuberous
sclerosis have an increased chance to develop certain behavioral
A unique brain finding in Tuberous sclerosis is
the cortical tuber, which is seen in about 90% of people with the
condition. The number and size of tubers in a person can correlate
with the degree of learning problems and seizures they may experience.
Other brain findings in Tuberous sclerosis include subependymal
hamartomas. Some of these may grow in childhood and block the normal
flow of spinal fluid, causing hydrocephalus. Brain tumors like subependymal
giant cell astrocytomas are a cause of health complications and
death in Tuberous sclerosis.
Since skin changes are so common in Tuberous sclerosis,
they can be some of the first signs of the condition that are noticed.
Ash-leaf spots are the most common skin finding, followed by facial
angiofibromas. These angiofibromas may cause slight disfigurement,
but more often are a cosmetic concern. Darkened skin patches called
cafe-au-lait spots may also occur, along with skin tags. Fortunately,
none of the skin symptoms usually cause serious medical complications.
Kidney disease can be a serious medical concern
in Tuberous sclerosis; it is the most frequent cause of death in
people with Tuberous sclerosis older than 30 years. The most common
renal finding is the angiomyolipoma, which is more commonly found
in women at a younger age. Though these growths are non-cancerous,
they can enlarge and disturb normal kidney function. Kidney cysts
may occur, again more commonly in younger women. These cysts may
be numerous and similarly disrupt normal kidney function as a result.
Renal cell carcinoma can be a further symptom of Tuberous sclerosis,
and kidney transplants may be necessary for any significant renal
Cardiac rhabdomyomas are typically seen in early
childhood, but occasionally may even be seen on a prenatal ultrasound.
Most rhabdomyomas disappear with age, remaining stable and causing
no symptoms; others may cause heart rhythm problems. Vascular disease
may also be a part of Tuberous sclerosis, with some people having
aneurysms of the abdomen and other areas of the body.
Lung problems are a part of Tuberous sclerosis,
and affect women more often. Lymphangioleimyomas of the lung are
common and affect about 1-4% of people with Tuberous sclerosis by
interfering with normal lung function. Hormones may be a factor
because pregnancy, menstruation, and estrogen have been associated
with a worsening of these symptoms in some women. Interestingly,
pulmonary problems have been associated with a milder case of Tuberous
sclerosis, often with fewer learning problems and seizures.
Other symptoms of Tuberous sclerosis include growths
on the retinas called hamartomas, which are not usually problematic.
There have been no typical ages in which eye involvement occurs
in Tuberous sclerosis.
Diagnosis of Tuberous sclerosis
Up until the discovery of TSC1 and TSC2, the diagnosis
of Tuberous sclerosis was made on a clinical basis. Criteria for
clinical diagnosis were updated in 1998 at the Tuberous Sclerosis
Complex Consensus Conference. The major features include:
• facial angiofibromas or forehead plaque
• non-traumatic ungual or periungual fibroma
• hypomelanotic macules (more than three)
• shagreen patch
• multiple retinal nodular hamartomas
• cortical tuber
• subependymal nodule
• subependymal giant cell astrocytoma
• cardiac rhabdomyoma, single or multiple
• renal angiomyolipoma.
The minor features include:
• multiple randomly distributed pits in dental
• bone cysts
• cerebral white matter radial migration lines
• gingival fibromas
• non-renal hamartoma
• retinal achromic patch
• "confetti" skin lesions
• multiple renal cysts.
Most brain findings in Tuberous sclerosis can
be identified with magnetic resonance imaging (MRI) or computed
tomography (CT) scans. Seizures can be documented from electroencephalogram
(EEG) monitoring. Skin changes are often found by using a Woods
lamp, which makes them more obvious during a physical examination.
Routine ultrasounds of the kidney often find and help monitor cysts
and angiomylipomas. Cardiac involvement may be seen as early as
a prenatal ultrasound, or with an echocardiogram in early life.
Electrocardiograms may be necessary to help detect heart rhythm
problems. For women in particular, a CT scan of the chest is important
to detect lung lymphangiomyomatosis. For all, an ophthalmology examination
is important to detect retinal involvement.
Genetic testing is available for Tuberous sclerosis
via gene sequencing. It is useful for confirming a clinical diagnosis,
prenatal diagnosis, or family testing when there is an identified
TSC mutation in the family. Sequencing of the TSC1 and TSC2 genes
is not perfect; it detects about 80% of people with Tuberous sclerosis.
An informative test result is one that identifies a known mutation
in either gene, and this confirms that the person has Tuberous sclerosis.
A negative test result does not identify a mutation in either gene.
This either means that the tested individual does not have Tuberous
sclerosis, or has a mutation that cannot be found through testing
and truly has the diagnosis.
Treatment for Tuberous sclerosis
Treatment for people with Tuberous sclerosis is
usually very specific to the person, since symptoms vary greatly.
The typical treatment team for someone with Tuberous sclerosis may
include a neurologist, neurosurgeon, medical geneticist, genetic
counselor, dermatologist, cardiologist, pulmonologist, nephrologist,
ophthalmologist, social worker, and a primary care provider. Often
times there are pediatric specialists in these fields who aid in
the care for children. Care providers in pediatric development are
particularly important, such as speech-language therapists and pediatric
There is no cure for Tuberous sclerosis. Therefore,
treatment is based upon symptoms. Seizures may be treated with various
anti-epilepsy medications. Those with significant seizures may be
tried on a ketogenic diet, which consists of frequent meals of high-fat
foods. While challenging, the ketogenic diet yields good results
in some cases.
Learning or behavioral problems are often serious
issues, but awareness and developmental interventions often help
families with Tuberous sclerosis. Pediatricians who have an interest
in child development are a good resource, particularly if a child
with Tuberous sclerosis is showing signs of autism.
Hydrocephalus can be serious and even lead to
learning problems if left untreated, so surgery to drain accumulated
fluid in the brain may be necessary. While most growths in the brain
are non-cancerous, brain tumors are typically treated as they would
be in someone without Tuberous sclerosis.
Since most skin complications of Tuberous sclerosis
cause no medical problems, treatment is not often necessary. Some
angiofibromas, particularly on the face, may be problematic and
require removal. Laser treatments may also be effective to reduce
the appearance of some skin changes.
Many kidney growths cause no health problem in
Tuberous sclerosis, but some individuals may have kidney cysts similar
to those found in polycystic kidney disease (Type 1). In these cases,
kidney function may be disturbed and the person might need a kidney
transplant after some time. Those with renal cell carcinoma would
be treated as anyone with this complication.
Most rhabdomyomas cause no problems, but some
may need surgery to keep their hearts working well. Surgery may
also be required for someone with a severe heart rhythm problem.
People with lung function problems may need to
be treated with medications, hormone therapy, or surgery if necessary.
Visual complaints are not as common for people
with Tuberous sclerosis, since retinal growths do not usually cause
symptoms. In rarer cases, vision may be disturbed and treated like
someone without Tuberous sclerosis.
Prognosis for Tuberous sclerosis
Prognosis for someone with tuberous sclerosis
is highly dependent upon symptoms they experience. Those who die
may do so as a result of significant neurological, pulmonary or
cardiac complications. People with Tuberous sclerosis often have
routine medical appointments dealing with symptoms as they arise.
Many people with Tuberous sclerosis survive into
adulthood, and studies are attempting to learn more about long-term
prognosis as people with Tuberous sclerosis age. It is challenging
to gain this information because older people with milder forms
of Tuberous sclerosis may not present for medical care frequently,
or may not even know they have the condition.
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Free Documentation. It is derivative of an article on Tuberous
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