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Tuberous Sclerosis (TS)
Tuberous sclerosis is a dominantly inherited genetic disorder in which tumors (usually hamartomas) develop in multiple organs. Diagnosis requires imaging of the affected organ. Treatment is symptomatic or, if CNS tumors are growing, everolimus. Patients must be monitored regularly to check for complications..
Tuberous sclerosis (TS) is a neurocutaneous syndrome that occurs in 1 of 6000 children; 85% of cases involve mutations in the TSC1 gene (9q34), which controls the production of hamartin, or the TSC2 gene (16p13.3), which controls the production of tuberin. These proteins act as growth suppressors. If either parent has the disorder, children have a 50% risk of having it. However, new mutations account for two thirds of cases.
Patients with tuberous sclerosis (sometimes called tuberous sclerosis complex) have tumors or abnormalities that manifest at different ages and in multiple organs, including the
CNS tubers interrupt neural circuits, causing developmental delay and cognitive impairment and may cause seizures, including infantile spasms. Sometimes the tubers grow and obstruct CSF flow from the lateral ventricles, causing unilateral hydrocephalus. Sometimes tubers undergo malignant degeneration into gliomas, particularly subependymal giant cell astrocytomas.
Cardiac myomas may develop prenatally, sometimes causing heart failure in neonates. These myomas tend to disappear over time and usually do not cause symptoms later in childhood or in adulthood.
Kidney tumors (angiolipomas) may develop in adults, and polycystic kidney disease may develop at any age. Kidney disease may cause hypertension.
Pulmonary lesions , such as lymphangioleiomyomatosis, may develop, particularly in adolescent girls.
Manifestations vary greatly in severity. Skin lesions are typically present.
Infants with CNS lesions may present with a type of seizure called infantile spasms. Affected children may also have other types of seizures, intellectual disability, autism, learning disorders, or behavioral problems.
Retinal patches are common and may be visible with funduscopy.
Pitting of enamel in permanent teeth is common.
Skin findings include
Initially pale, ash leaf–shaped macules, which develop during infancy or early childhood
Angiofibromas of the face (adenoma sebaceum), which develop during later childhood
Congenital shagreen patches (raised lesions resembling an orange peel), usually on the back
Subungual fibromas, which can develop any time during childhood or early adulthood
TS may be suspected when fetal ultrasonography detects cardiac myomas or when infantile spasms occur.
Physical examination is done to check for typical skin lesions. Funduscopy should be done to check for retinal patches.
Cardiac or cranial manifestations may be visible on routine prenatal ultrasonography. MRI or ultrasonography of the affected organs is necessary for confirmation.
Specific genetic testing is available.
Treatment is both symptomatic and specific:
For seizures: Anticonvulsants (especially vigabatrin for infantile spasms) or sometimes epilepsy surgery
For skin lesions: Dermabrasion or laser techniques
For neurobehavioral problems: Behavior management techniques or drugs
For hypertension caused by renal problems: Antihypertensives or surgery to remove growing tumors
For developmental delays: Special schooling or occupational therapy
For malignant tumors and some of the benign tumors: Everolimus
Genetic counseling is indicated for adolescents and adults of childbearing age.
All patients should be screened regularly to detect complications early.
Typically, the following is done:
MRI of the head to check for intracranial complications at least every 3 yr
Renal ultrasonography to check for kidney tumors every 3 yr in school-aged children and every 1 to 2 yr in adults
Chest x-ray in girls in their late teens
Neuropsychologic testing periodically in children to help plan for support at school
Use of sirolimus and its derivative, everolimus, to prevent and treat most of the complications of TS is under study.
Clinical monitoring is also important and sometimes prompts more frequent testing. Development of headaches, loss of skills, or new kinds of seizures may be caused by malignant degeneration or growth of CNS tubers and are indications for neuroimaging.
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