NeurometPlus

Incidence

Tuberous sclerosis is an autosomal dominant disorder with variable expression and incomplete penetrance. Approximately 50,000 people in the United Sates have TSC. TSC occurs in all races and ethnic groups. The disease affects an estimated 1 in 6,000 newborns. Other authorities think it has an incidence of 1/10,000 births. About 1/3 of all people with TSC genetically inherit the disease, while in the remaining individuals, the disease is acquired as a result of spontaneous genetic mutation. New mutations constitute about 75% of the cases.

Clinical Characteristics

Tuberous sclerosis is a rare genetic, neurological disorder primarily characterized by seizures, mental retardation, and skin and eye lesions. In some cases, neurobehavioral problems may also occur. This condition is considered a neurocutaneous syndrome or phakomatosis. Individuals with tuberous sclerosis may experience none or all of the symptoms with varying degrees of severity. Tuberous sclerosis is a multi-system disease that can affect the brain, kidneys, heart, eyes, lungs, and other organs. Small benign tumors may grow on the face and eyes, as well as in the brain, kidneys, and other organs. Neuroimaging studies may be able to confirm the diagnosis. Seizures most often begin in the first year of life. Tuberous sclerosis in the neonatal period has three presentations: (1) hypopigmented spots; (2) cardiac rhabdomyomas; and (3) seizures. The most frequent presentation is multiple hypopigmented spots on the trunk and limbs. The hypopigmented spots are flat and the edges irregular but sharply delineated. Their shape resembles an ash leaf or an arrow head. The hypopigmented spots may be difficult to see in neonates with light-skin. A Wood\\\'s lamp examination may \\\"bring them out.\\\" The diagnosis of tuberous sclerosis can be made if seizures occur in a neonate with one typical hypopigmented spot. In the absence of neonatal seizures, the question of how many typical depigmented spots are needed to diagnose tuberous sclerosis has not been determined. The best approach to a patient with one typical or few atypical depigmented spots but without seizures is to perform ultrasonography of the brain, heart, and kidneys. A brain CT should also be done. The presence of a typical tuberous sclerosis lesion in any of these organs establishes the diagnosis. The second most frequent presentation is a heart murmur secondary to cardiac rhabdomyomas. Cardiac rhabdomyomas are readily discovered by ultrasound. The third most frequent presentation is seizures due to cortical tubers. Hydrocephalus due to subependymal hamartomas may also occur. Renal abnormalities seldom produce clinical manifestations in the neonatal period. Neonates with tuberous sclerosis should undergo ultrasound of the heart, kidney, and brain. Magnetic resonance imaging of the brain should be performed as soon as the diagnosis of tuberous sclerosis is made. The brain lesions found in patients with tuberous sclerosis are: white matter anomalities, cortical tubers, subependymal nodules, subependymal giant cell astrocytomas, and cysts. All of the lesions of tuberous sclerosis that occur in the neonatal period and early infancy (white matter anomalies, subependymal nodules, and subependymal giant cell astrocytomas) are hyperintense (white) on T1-weighted images and hypointense (black) on T2-weighted images. White matter lesions and subependymal giant cell astrocytomas are more readily detected in neonates and in young infants, whereas cortical tubers may not be. Lesions in the temporal lobe may indicate a high incidence of infantile spasm. Cortical tubers, unlike most of the lesions that occur in neonates, are hyperintense on T2-weighted images. Brain computed tomography may show periventricular calcification even in the neonatal period. Antiepileptic drugs may control the seizures. Phenobarbital is the first choice. The possibility of epilepsy surgery should be considered in these patients. Vigabatrim (Sabril) is an effective treatment for infantile spasm in infants with tuberous sclerosis. Vigabatrim has not been used in neonates. Tuberous Sclerosis results from changes (mutations) in a gene or genes that may occur spontaneously (sporadically) for unknown reasons or be inherited as an autosomal dominant trait. Most cases represent new (sporadic) gene mutations, with no family history of the disease. Mutations of at least two different genes are known to cause Tuberous Sclerosis. One gene (TSC1) has been mapped to the long arm (q) of chromosome 9 (9q34). A second gene for the disease (TSC2) is located on the short arm (p) of chromosome 16 (16p13.3). It remains unclear whether some sporadic and familial cases of the disease may be caused by mutations of other, currently unidentified genes (genetic heterogeneity). Some authors consider this condition an epileptic syndrome. In summary, this condition is characterized by the formation of hamartomas, which are noncancerous tumor-like masses. These tumors can form in major organs including the brain, skin, eyes and kidneys. Tumors in the heart often occur in children, while lung tumors can occur in adults. Symptoms of TSC can range from mild to severe and can change over time. TSC may not be noticeable. Because symptoms vary and may not be immediately recognized by a health care provider, TSC is often undiagnosed for years.

Precipitants

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Provocation Tests

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Diagnostic Procedures

It is a clinical diagnosis. A triad of epilepsy, mental retardation, and angiofibromas of numerous organs with intracranial hamartomatous lesions involving subependymal nodules and cerebral cortical tubers, hence the name \"tuberous sclerosis\". Hypochromic birth marks are always present in the skin. A mutation in the TSC1 or TSC2 gene is sufficient to diagnose in these TSC. However, 10% to 25% of TSC patients show no mutations in these genes. If a genetic test outcome is normal, or if testing is unavailable, the use of clinical diagnostic criteria is necessary for an accurate diagnosis. Definite Diagnosis: 2 major features or 1 major feature with greater/equal 2 minor features. Possible Diagnosis: 1 major feature or greater/equal 2 minor features. Major Features are: 1. Hypomelanotic macules (greater/equal 3, at least 5mm diameter). 2. Angiofibromas (greater/equal 3) or fibrous cephalic plaque. 3. Ungual fibromas (greater/equal 2). 4. Shagreen patch. 5. Multiple retinal hamartomas. 6. Cortical dysplasias (Tubers and cerebral white matter radial migration lines). 7. Subependymal nodules. 8. Subependymal Giant Cell Astrocytoma (SEGA). 9. Cardiac rhabdomyoma. 10. Lymphanioleiomyomatosis (LAM). 11. Angiomyolipomas (greater/equal 2). Minor Features are: 1. “Confetti” skin lesions. 2. Dental enamel pits. 3. Intraoral fibromas (greater/equal 2). 4. Retinal achromic patch. 5. Multiple renal cysts. 6. Nonrenal hamartomas.