Imaging Studies
Evaluation of newly diagnosed tuberous sclerosis patients should include a personal and family history and a clinical examination, including funduscopy, cranial imaging (eg, MRI, nonenhanced CT scanning), renal ultrasonography, and echocardiography in infants.
Computed cranial tomography scanning and MRI are performed not only in suspect cases but also in patients whose diagnosis is obvious. Do not use scan results to predict the neurologic outcome of an individual patient. New MRI techniques such as FLAIR (fluid attenuated inversion recovery) help identify small tubers, which may not be detected with other imaging techniques. [32]
If tubers are present, serial imaging scans are essential to evaluate for growth of the tumor.
EEG is useful when the initial presentation includes epileptic seizures. EEG is not required in children who do not have epilepsy.
Renal ultrasonography is used to evaluate children and older patients in particular for renal tumors.
ECG is a baseline study essential to detect any cardiac arrhythmias. Wolff-Parkinson-White syndrome seems to be the most common arrhythmia in patients with tuberous sclerosis complex (TSC).
Echocardiography is recommended for patients of any age with symptoms of cardio rhabdomyoma. Because most symptoms occur in neonates, older children do not need to have an echocardiogram, unless it is to confirm a previous dubious diagnosis.
Neurodevelopmental testing as age-appropriate screening for behavioral and neurodevelopmental dysfunction at the time of diagnosis is essential. Periodically reassess children with abnormal test results. Newly diagnosed adults with normal social and cognitive function (as demonstrated by educational and career achievements) may not require formal testing. Frequent assessment is probably not warranted in such individuals.
Consensus guidelines have been published to help in the assessment of cognitive and behavioral problems in persons with tuberous sclerosis complex. Refer to the Tuberous Sclerosis Association for the guidelines.
Molecular diagnosis using DNA-based testing is not yet routinely available but in the future could be developed and would help to identify patients at increased or decreased risk for particular complications.
Ongoing evaluation
Annual or at least biannual MRI can be performed until age 21 years. At that point, any single tumors identified may need closer monitoring.
The frequency of EEG depends upon the clinical features and the treatment response of epilepsy. Consider EEG in the evaluation of a patient with unexplained decline of behavioral or cognitive function, in whom epileptic seizures are suspected.
Neurodevelopmental testing should take into account various features of tuberous sclerosis complex, including mental retardation, which is the most common, and other features, which are learning disabilities, autism, and attentional deficit. Repeat assessment around the time that a child enters school and then reassess periodically in response to educational and behavioral concerns.
Renal ultrasonography is recommended annually. Patients who have large renal lesions or lesions that have grown substantially should have more frequent follow-up examinations.
ECG is indicated in persons with arrhythmias or unexplained loss of consciousness. Repeat echocardiography is not required in asymptomatic patients. Any suggestion of cardiac dysfunction may merit investigations.
Pulmonary function testing is reserved for patients with pulmonary dysfunction and may be performed annually. Women should undergo chest CT scanning at least once on reaching adulthood.
Evaluation of family members
In a family with only one child affected, evaluation of parents is more important than siblings or relatives.
Cranial CT scanning is more likely to detect lesions of tuberous sclerosis as a screening tool; MRI often detects lesions that are not as specific to tuberous sclerosis complex. MRI is the first choice; however, if the scan results are negative and the diagnosis is uncertain, then CT scanning may be performed.
Renal lesions occur in about 80% of patients, making renal ultrasonography an important screening test.
Echocardiography is not recommended unless compelling cardiac symptoms persuade otherwise because cardiac rhabdomyomas commonly disappear by adulthood.
Although molecular diagnosis is not yet commercially available, identifying some patients with tuberous sclerosis complex who do not fulfill clinical diagnostic criteria should soon be feasible.
Histologic Findings
Angiofibromas show atrophic sebaceous glands with dermal fibrosis and dilation of some of the capillaries. The fibrosis occasionally has a glial appearance because of the large size and stellate shape of the fibroblasts. Elastic tissue is absent in the angiofibromas.
The ungual fibromas show mainly fibrosis, rarely capillary dilation.
The shagreen patches show increased dense sclerotic mass of broad collagenous bundles. Normal collagen bundles may sometimes be arranged in an interwoven pattern. The elastic tissue is reduced.
The hypopigmented ash-leaf macule shows normal melanocyte numbers with decreased pigmentation. Electron microscopy shows smaller melanosomes with defective melanization.
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Facial angiofibromas in a young man with tuberous sclerosis complex.
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Dysplastic periungual fibroma involving the great toe in a patient with tuberous sclerosis.
Tables
Major Features |
Minor Features |
Hypomelanotic macules (≥3, at least 5 mm in diameter) |
Confetti skin lesions |
Angiofibromas (≥3) or fibrous cephalic plaque |
Dental enamel pits (>3) |
Ungual fibromas (≥2) |
Intraoral fibromas (≥2) |
Shagreen patch |
Retinal achromatic patch |
Multiple retinal hamartomas |
Multiple renal cysts |
Cortical dysplasiasa |
Nonrenal hamartomas |
Subependymal nodules |
|
Subependymal giant cell astrocytoma |
|
Cardiac rhabdomyoma |
|
Lymphangioleiomyomatosis (LAM) plus |
|
Angiomyolipomas (≥2)b |
|
a Includes tubers and cerebral white matter radial migration lines. b A combination of the two major clinical features (LAM and angiomyolipomas) without other features does not meet criteria for a definite diagnosis. |
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