Penetrance

The penetrance of TSC appears to be 100%. Rare instances of apparent non-penetrance have been reported; however, molecular studies revealed the presence of two different pathogenic variants in the family and gonadal mosaicism in others .

Source: GeneReviews — "Tuberous Sclerosis Complex"

Diagnostic Criteria

Consensus clinical diagnostic criteria for tuberous sclerosis complex (TSC) have been published (full text).

Suggestive Findings

TSC should be suspected in individuals with either one major clinical feature or two or more minor features.

Major features

• Hypomelanotic macules (≥3 macules that are at least 5 mm in diameter)

• Angiofibromas (≥3) or fibrous cephalic plaque

• Shagreen patch

• Ungual fibromas (≥2)

• Subependymal nodules (SENs) (≥2)

• Multiple cortical tubers and/or radial migration lines

• Subependymal giant cell astrocytoma (SEGA)

• Renal angiomyolipomas (≥2) (See , *Note.)

• Cardiac rhabdomyoma

• Lymphangioleiomyomatosis (LAM) (See , *Note.)

• Multiple retinal nodular hamartomas

Minor features

Source: GeneReviews — "Tuberous Sclerosis Complex"

Management Guidelines

Consensus clinical management and surveillance recommendations for individuals with tuberous sclerosis complex (TSC) have been published (full text).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with TSC, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended by the International Tuberous Sclerosis Consensus Conference (full text).

Table 4.

Tuberous Sclerosis Complex: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Skin | Detailed dermatologic exam |

Central nervous system

| Brain MRI for tubers, SENs, migrational defects, SEGAs |

• Neurologic eval for manifestations of seizures

• Baseline EEG while awake asleep

• During infancy, educate parents to recognize infantile spasms as well as other seizure types even if none have occurred at time of diagnosis.

| • Infantile spasms are a neurologic emergency in infants w/TSC requiring immediate eval treatment.

• If baseline EEG is abnormal or if TAND is present: 24-hr video EEG to assess for subclinical seizure activity

• Earlier recognition treatment of epilepsy in infancy is assoc w/better long-term neurologic outcome.

• Parent/caregiver education training re TAND manifestations (e.g., ASD, ADHD, language anxiety disorders)

• Comprehensive eval for all manifestations using TAND Checklist1

| • To ensure families are monitoring for emerging TAND manifestations1

Source: GeneReviews — "Tuberous Sclerosis Complex"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended (adapted from , Table 3).

Table 7.

Tuberous Sclerosis Complex: Recommended Surveillance

System/Concern | Evaluation | Frequency

Skin | Detailed clinical dermatologic exam | Annually

SEGAs

| Brain MRI | In those w/o SEGAs: every 1-3 yrs until age 25 yrs in asymptomatic persons (no CNS-related symptoms) to monitor for new occurrence of SEGAs

In those w/known asymptomatic SEGAs:

• Continue imaging periodically throughout adulthood to monitor for SEGA growth.

• For large or growing SEGAs causing ventricular enlargement w/o symptoms, brain MRI should be performed more frequently; these persons their families should be educated re potential for new symptoms.

Seizures

| Assessment w/neurologist for clinical manifestations of seizures | At each visit

EEG | • In asymptomatic infants: every 6 wks up to age 12 mos; every 3 mos up to age 24 mos1

• In those w/known or suspected seizures: as clinically indicated

• If infantile spams or focal seizures are suspected but cannot be confirmed clinically or on routine EEG, prolonged video EEG that includes sleep should be performed.

TAND | Screening for TAND using validated screening tools (e.g., TAND Checklist) | At least annually or more frequently as needed

Source: GeneReviews — "Tuberous Sclerosis Complex"