| Tuberous Sclerosis is a rare disease that causes growths in the skin, brain, kidneys, eyes, heart or lungs. Bright Tots Information on child development |
|
| Tuberous Sclerosis |
Tuberous sclerosis also called tuberous sclerosis complex (TSC) is a rare disease that causes growths in the skin,
brain, kidneys, eyes, heart or lungs. These growths are usually benign (non-cancerous). The first signs of tuberous
sclerosis may be seizures and spots on the skin. Some people who have tuberous sclerosis may have learning problems
or seizures that are hard to control. It commonly affects the central nervous system and results in a mixture of
symptoms including seizures, developmental delay, behavioral problems, skin abnormalities, and kidney disease.
Tuberous sclerosis affects every 1 in 6,000 people in the United States. The disorder occurs in both sexes and in people
of all races and ethnic groups. The disorder affects as many as 25,000 to 40,000 individuals in the United States and
about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns.
Many tuberous sclerosis complex patients show indication of the disorder in the first year of life. However, clinical
features can be faint initially, and many signs and symptoms take years to develop. As a result, tuberous sclerosis can
be unrecognized or misdiagnosed for years.
What causes Tuberous Sclerosis?
Tuberous sclerosis is caused by defects, or mutations, on two genes-TSC1 and TSC2. Only one of the genes needs to
be affected for tuberous sclerosis complex 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 Tuberous Sclerosis complex brain lesions.
In familial cases, tuberous sclerosis is an autosomal dominant disorder, which means that the disorder can be
transmitted directly from parent to child. In those cases, only one parent needs to have the faulty gene in order to pass
it on to a child. If a parent has tuberous sclerosis gene, each offspring has a 50 percent chance of developing the
disorder. Children who inherit tuberous sclerosis complex may not have the same symptoms as their parent and they
may have either a milder or a more severe form of the disorder.
Currently, there is no test to identify a person who has the tuberous sclerosis gene if that person has no signs or
symptoms of it. If parents who have one child with tuberous sclerosis want to have another child, they should talk with
their family doctor. The family doctor can refer them to a genetic counselor or medical geneticist who can help them
with additional facts.
Although some individuals inherit the disorder from a parent with tuberous sclerosis complex, 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.
Rarely, individuals acquire tuberous sclerosis complex through a process called gonadal mosaicism. These patients have
parents with no apparent defects in the two genes that cause the disorder. Yet these parents can have a child with
tuberous sclerosis because a portion of one of the parent's reproductive cells (sperm or eggs) can contain the genetic
mutation without the other cells of the body being involved. In cases of gonadal mosaicism, genetic testing of a blood
sample might not reveal the potential for passing the disease to offspring.
Symptoms of Tuberous Sclerosis
Tuberous sclerosis complex can affect many different systems of the body, causing a variety of signs and symptoms.
Signs of the disorder vary depending on which organism and which limbs are involved. The natural course of tuberous
sclerosis complex varies from individual to individual, with symptoms ranging from very mild to quite severe. In
addition to the benign tumors that frequently occur in tuberous sclerosis, other common symptoms include seizures,
mental retardation, behavior problems, and skin abnormalities. Tumors can grow in nearly any organ, but they most
commonly occur in the brain, kidneys, heart, lungs, and skin. Malignant tumors are rare in tuberous sclerosis complex.
Those that do occur primarily affect the kidneys.
Kidney problems such as cysts and angiomyolipomas occur in an estimated 70 to 80 percent of individuals with
tuberous sclerosis, usually occurring between ages 15 and 30. Cysts are usually small, appear in limited numbers, and
cause no serious problems. Approximately 2 percent of individuals with tuberous sclerosis complex develop large
numbers of cysts in a pattern similar to polycystic kidney disease during childhood. In these cases, kidney function is
compromised and kidney failure occurs. In rare instances, the cysts may bleed, leading to blood loss and anemia.
Three types of brain tumors are associated with tuberous sclerosis complex: cortical tubers, for which the disease is
named, generally form on the surface of the brain, but may also appear in the deep areas of the brain; subependymal
nodules, which form in the walls of the ventricles-the fluid-filled cavities of the brain; and giant-cell tumors
(astrocytomas), a type of tumor that can grow and block the flow of fluids within the brain, causing a buildup of fluid
and pressure and leading to headaches and blurred vision.
Tumors called cardiac rhabdomyomas are often found in the hearts of infants and young children with tuberous
sclerosis. If the tumors are large or there are multiple tumors, they can block circulation and cause death. However, if
they do not cause problems at birth-when in most cases they are at their largest size-they usually become smaller with
time and do not affect the individual in later life.
Benign tumors called phakomas are sometimes found in the eyes of individuals with tuberous sclerosis complex,
appearing as white patches on the retina. Generally they do not cause vision loss or other vision problems, but they can
be used to help diagnose the disease. Additional tumors and cysts may be found in other areas of the body, including
the liver, lung, and pancreas. Bone cysts, rectal polyps, gum fibromas, and dental pits may also occur.
A wide variety of skin abnormalities may occur in individuals with tuberous sclerosis. Most cause no problems but are
helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin
abnormalities include:
• Hypomelanic macules ("ash leaf spots"), which are white or lighter patches of skin that appear anywhere on the
body and are caused by a lack of skin pigment or melanin-the substance that gives skin its color.
• Reddish spots or bumps called facial angiofibromas (also called adenoma sebaceum), which appear on the face
(sometimes resembling acne) and consist of blood vessels and fibrous tissue.
• Raised, discolored areas on the forehead called forehead plaques, which are common and unique to tuberous
sclerosis complex and may help doctors diagnose the disorder.
• Areas of thick leathery, pebbly skin called shagreen patches, usually found on the lower back or nape of the neck.
• Small fleshy tumors called ungual or subungual fibromas that grow around and under the toenails or fingernails
and may need to be surgically removed if they enlarge or cause bleeding. These usually appear later in life, ages 20 - 50.
• Other skin features that are not unique to individuals with tuberous sclerosis complex, including molluscum
fibrosum or skin tags, which typically occur across the back of the neck and shoulders, café au lait spots or flat brown
marks, and poliosis, a tuft or patch of white hair that may appear on the scalp or eyelids.
Mental Ability of Children with Tuberous Sclerosis Complex
Approximately one-half to two-thirds of individuals with tuberous sclerosis complex have mental disabilities ranging
from mild learning disabilities to severe mental retardation. Behavior problems, including aggression, sudden rage,
attention deficit hyperactivity disorder, acting out, obsessive-compulsive disorder, and repetitive, destructive, or self-
harming behavior, often occur in children with tuberous sclerosis, and can be difficult to manage. Some individuals
with tuberous sclerosis complex may also have a developmental disorder called autism.
Tuberous sclerosis can cause seizures and varying degrees of mental disability. Seizures of all types may occur,
including infantile spasms; tonic-clonic seizures (also known as grand mal seizures); or tonic, akinetic, atypical
absence, myoclonic, complex partial, or generalized seizures.
Your doctor may suspect tuberous sclerosis if your baby has a condition called cardiac rhabdomyomas (benign heart
tumors) at birth or starts to have seizures, especially a kind of seizure called infantile spasms.
Diagnosis of Tuberous Sclerosis Complex
In most cases the first clue to recognizing tuberous sclerosis complex is the presence of seizures or delayed
development. In other cases, the first sign may be white patches on the skin (hypomelanotic macules). 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. Doctors should carefully examine the skin for the wide variety of skin
features, the fingernails and toenails for ungual fibromas, the teeth and gums for dental pits and/or gum fibromas, and
the eyes for dilated pupils. A Wood's lamp or ultraviolet light may be used to locate the hypomelantic macules which
are sometimes hard to see on infants and individuals with pale or fair skin. Because of the wide variety of signs of
tuberous sclerosis complex it is best if a doctor experienced in the diagnosis of tuberous sclerosis complex evaluates a
potential patient.
In infants tuberous sclerosis complex may be suspected if the child has cardiac rhabdomyomas or seizures (infantile
spasms) at birth. With a careful examination of the skin and brain, it may be possible to diagnose tuberous sclerosis
complex in a very young infant. However, many children are not diagnosed until later in life when their seizures begin
and other symptoms such as facial angiofibromas appear.
Tuberous Sclerosis Treatment
Unfortunately, there is no cure for tuberous sclerosis, although treatment is available for a number of the symptoms.
For example, medicine can help control seizures and surgery can remove any growths. If your child has developmental
problems, occupational therapy can help. Most people who have tuberous sclerosis have a normal life span.
Treatment for tuberous sclerosis antiepileptic drugs 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 is useful
treatment for skin lesions. Some with the tuberous sclerosis is a lifelong condition; individuals need to be regularly
monitored by a doctor to make sure they are receiving the best possible treatments. Due to the many varied symptoms
of tuberous sclerosis complex, care by a clinician experienced with the disorder is recommended.
Tuberous Sclerosis Complex Prognosis
The prognosis for individuals with tuberous sclerosis complex depends on the severity of symptoms, which range from
mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe mental retardation,
uncontrollable seizures, and kidney failure. Those individuals with mild symptoms generally do well and live long
productive lives, while individuals with the more severe form may have serious disabilities.
In rare cases, seizures, infections, or tumors in vital organs may cause complications in some organs such as the
kidneys and brain that can lead to severe difficulties and even death. However, with appropriate medical care, most
individuals with the disorder can look forward to normal life expectancy.
brain, kidneys, eyes, heart or lungs. These growths are usually benign (non-cancerous). The first signs of tuberous
sclerosis may be seizures and spots on the skin. Some people who have tuberous sclerosis may have learning problems
or seizures that are hard to control. It commonly affects the central nervous system and results in a mixture of
symptoms including seizures, developmental delay, behavioral problems, skin abnormalities, and kidney disease.
Tuberous sclerosis affects every 1 in 6,000 people in the United States. The disorder occurs in both sexes and in people
of all races and ethnic groups. The disorder affects as many as 25,000 to 40,000 individuals in the United States and
about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns.
Many tuberous sclerosis complex patients show indication of the disorder in the first year of life. However, clinical
features can be faint initially, and many signs and symptoms take years to develop. As a result, tuberous sclerosis can
be unrecognized or misdiagnosed for years.
What causes Tuberous Sclerosis?
Tuberous sclerosis is caused by defects, or mutations, on two genes-TSC1 and TSC2. Only one of the genes needs to
be affected for tuberous sclerosis complex 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 Tuberous Sclerosis complex brain lesions.
In familial cases, tuberous sclerosis is an autosomal dominant disorder, which means that the disorder can be
transmitted directly from parent to child. In those cases, only one parent needs to have the faulty gene in order to pass
it on to a child. If a parent has tuberous sclerosis gene, each offspring has a 50 percent chance of developing the
disorder. Children who inherit tuberous sclerosis complex may not have the same symptoms as their parent and they
may have either a milder or a more severe form of the disorder.
Currently, there is no test to identify a person who has the tuberous sclerosis gene if that person has no signs or
symptoms of it. If parents who have one child with tuberous sclerosis want to have another child, they should talk with
their family doctor. The family doctor can refer them to a genetic counselor or medical geneticist who can help them
with additional facts.
Although some individuals inherit the disorder from a parent with tuberous sclerosis complex, 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.
Rarely, individuals acquire tuberous sclerosis complex through a process called gonadal mosaicism. These patients have
parents with no apparent defects in the two genes that cause the disorder. Yet these parents can have a child with
tuberous sclerosis because a portion of one of the parent's reproductive cells (sperm or eggs) can contain the genetic
mutation without the other cells of the body being involved. In cases of gonadal mosaicism, genetic testing of a blood
sample might not reveal the potential for passing the disease to offspring.
Symptoms of Tuberous Sclerosis
Tuberous sclerosis complex can affect many different systems of the body, causing a variety of signs and symptoms.
Signs of the disorder vary depending on which organism and which limbs are involved. The natural course of tuberous
sclerosis complex varies from individual to individual, with symptoms ranging from very mild to quite severe. In
addition to the benign tumors that frequently occur in tuberous sclerosis, other common symptoms include seizures,
mental retardation, behavior problems, and skin abnormalities. Tumors can grow in nearly any organ, but they most
commonly occur in the brain, kidneys, heart, lungs, and skin. Malignant tumors are rare in tuberous sclerosis complex.
Those that do occur primarily affect the kidneys.
Kidney problems such as cysts and angiomyolipomas occur in an estimated 70 to 80 percent of individuals with
tuberous sclerosis, usually occurring between ages 15 and 30. Cysts are usually small, appear in limited numbers, and
cause no serious problems. Approximately 2 percent of individuals with tuberous sclerosis complex develop large
numbers of cysts in a pattern similar to polycystic kidney disease during childhood. In these cases, kidney function is
compromised and kidney failure occurs. In rare instances, the cysts may bleed, leading to blood loss and anemia.
Three types of brain tumors are associated with tuberous sclerosis complex: cortical tubers, for which the disease is
named, generally form on the surface of the brain, but may also appear in the deep areas of the brain; subependymal
nodules, which form in the walls of the ventricles-the fluid-filled cavities of the brain; and giant-cell tumors
(astrocytomas), a type of tumor that can grow and block the flow of fluids within the brain, causing a buildup of fluid
and pressure and leading to headaches and blurred vision.
Tumors called cardiac rhabdomyomas are often found in the hearts of infants and young children with tuberous
sclerosis. If the tumors are large or there are multiple tumors, they can block circulation and cause death. However, if
they do not cause problems at birth-when in most cases they are at their largest size-they usually become smaller with
time and do not affect the individual in later life.
Benign tumors called phakomas are sometimes found in the eyes of individuals with tuberous sclerosis complex,
appearing as white patches on the retina. Generally they do not cause vision loss or other vision problems, but they can
be used to help diagnose the disease. Additional tumors and cysts may be found in other areas of the body, including
the liver, lung, and pancreas. Bone cysts, rectal polyps, gum fibromas, and dental pits may also occur.
A wide variety of skin abnormalities may occur in individuals with tuberous sclerosis. Most cause no problems but are
helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin
abnormalities include:
• Hypomelanic macules ("ash leaf spots"), which are white or lighter patches of skin that appear anywhere on the
body and are caused by a lack of skin pigment or melanin-the substance that gives skin its color.
• Reddish spots or bumps called facial angiofibromas (also called adenoma sebaceum), which appear on the face
(sometimes resembling acne) and consist of blood vessels and fibrous tissue.
• Raised, discolored areas on the forehead called forehead plaques, which are common and unique to tuberous
sclerosis complex and may help doctors diagnose the disorder.
• Areas of thick leathery, pebbly skin called shagreen patches, usually found on the lower back or nape of the neck.
• Small fleshy tumors called ungual or subungual fibromas that grow around and under the toenails or fingernails
and may need to be surgically removed if they enlarge or cause bleeding. These usually appear later in life, ages 20 - 50.
• Other skin features that are not unique to individuals with tuberous sclerosis complex, including molluscum
fibrosum or skin tags, which typically occur across the back of the neck and shoulders, café au lait spots or flat brown
marks, and poliosis, a tuft or patch of white hair that may appear on the scalp or eyelids.
Mental Ability of Children with Tuberous Sclerosis Complex
Approximately one-half to two-thirds of individuals with tuberous sclerosis complex have mental disabilities ranging
from mild learning disabilities to severe mental retardation. Behavior problems, including aggression, sudden rage,
attention deficit hyperactivity disorder, acting out, obsessive-compulsive disorder, and repetitive, destructive, or self-
harming behavior, often occur in children with tuberous sclerosis, and can be difficult to manage. Some individuals
with tuberous sclerosis complex may also have a developmental disorder called autism.
Tuberous sclerosis can cause seizures and varying degrees of mental disability. Seizures of all types may occur,
including infantile spasms; tonic-clonic seizures (also known as grand mal seizures); or tonic, akinetic, atypical
absence, myoclonic, complex partial, or generalized seizures.
Your doctor may suspect tuberous sclerosis if your baby has a condition called cardiac rhabdomyomas (benign heart
tumors) at birth or starts to have seizures, especially a kind of seizure called infantile spasms.
Diagnosis of Tuberous Sclerosis Complex
In most cases the first clue to recognizing tuberous sclerosis complex is the presence of seizures or delayed
development. In other cases, the first sign may be white patches on the skin (hypomelanotic macules). 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. Doctors should carefully examine the skin for the wide variety of skin
features, the fingernails and toenails for ungual fibromas, the teeth and gums for dental pits and/or gum fibromas, and
the eyes for dilated pupils. A Wood's lamp or ultraviolet light may be used to locate the hypomelantic macules which
are sometimes hard to see on infants and individuals with pale or fair skin. Because of the wide variety of signs of
tuberous sclerosis complex it is best if a doctor experienced in the diagnosis of tuberous sclerosis complex evaluates a
potential patient.
In infants tuberous sclerosis complex may be suspected if the child has cardiac rhabdomyomas or seizures (infantile
spasms) at birth. With a careful examination of the skin and brain, it may be possible to diagnose tuberous sclerosis
complex in a very young infant. However, many children are not diagnosed until later in life when their seizures begin
and other symptoms such as facial angiofibromas appear.
Tuberous Sclerosis Treatment
Unfortunately, there is no cure for tuberous sclerosis, although treatment is available for a number of the symptoms.
For example, medicine can help control seizures and surgery can remove any growths. If your child has developmental
problems, occupational therapy can help. Most people who have tuberous sclerosis have a normal life span.
Treatment for tuberous sclerosis antiepileptic drugs 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 is useful
treatment for skin lesions. Some with the tuberous sclerosis is a lifelong condition; individuals need to be regularly
monitored by a doctor to make sure they are receiving the best possible treatments. Due to the many varied symptoms
of tuberous sclerosis complex, care by a clinician experienced with the disorder is recommended.
Tuberous Sclerosis Complex Prognosis
The prognosis for individuals with tuberous sclerosis complex depends on the severity of symptoms, which range from
mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe mental retardation,
uncontrollable seizures, and kidney failure. Those individuals with mild symptoms generally do well and live long
productive lives, while individuals with the more severe form may have serious disabilities.
In rare cases, seizures, infections, or tumors in vital organs may cause complications in some organs such as the
kidneys and brain that can lead to severe difficulties and even death. However, with appropriate medical care, most
individuals with the disorder can look forward to normal life expectancy.
| ________________________________________________________________________________________________________________________ Copyright © 2004 Bright Tots® Inc. - Educational Toys & Resource Guide to Child Development - All rights reserved. ________________________________________________________________________________________________________________________ |
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