The packet describes tuberous sclerosis as a hereditary disease. GeneReviews states that the molecular diagnosis is established by identification of a heterozygous pathogenic (or likely pathogenic) variant through molecular genetic testing. A specific gene list and an inheritance-pattern field are not certified in this packet, so no gene-level or inheritance-pattern claims are made here.

GeneReviews reports that about one third of individuals diagnosed with TSC have an affected parent, and that two thirds have the disorder as the result of a de novo pathogenic variant. It also reports that the penetrance of TSC appears to be 100%, with rare instances of apparent non-penetrance described.

The packet also lists two subtypes, tuberous sclerosis 1 and tuberous sclerosis 2.

GeneReviews describes consensus clinical diagnostic criteria for TSC. TSC is suspected in individuals with either one major clinical feature or two or more minor features.

Major features listed are: hypomelanotic macules (three or more, at least 5 mm in diameter); angiofibromas (three or more) or fibrous cephalic plaque; shagreen patch; ungual fibromas (two or more); subependymal nodules (two or more); multiple cortical tubers and/or radial migration lines; subependymal giant cell astrocytoma; renal angiomyolipomas (two or more); cardiac rhabdomyoma; lymphangioleiomyomatosis; and multiple retinal nodular hamartomas.

Minor features listed are: "confetti" skin lesions; sclerotic bone lesions; dental enamel pits; intraoral fibromas (two or more); multiple renal cysts (two or more); extrarenal hamartomas; and retinal achromic patch.

According to GeneReviews, a definite clinical diagnosis can be established with two major features, or one major feature plus two or more minor features. The combination of LAM and renal angiomyolipomas without additional features does not meet the criteria for a definite diagnosis. A molecular diagnosis is established by a heterozygous pathogenic or likely pathogenic variant identified by molecular genetic testing, and because clinical manifestations develop over time, identification of such a variant is sufficient to establish the diagnosis. Testing approaches described include concurrent gene testing or a multigene panel. A variant of uncertain significance neither establishes nor rules out the diagnosis. GeneReviews states that if no pathogenic variant is identified, somatic mosaicism is considered,.

GeneReviews describes management as covering evaluations following diagnosis, targeted therapies, treatment of manifestations, and supportive care. Its targeted therapy table lists mTOR inhibitors (the rapalogs sirolimus and everolimus). GeneReviews describes supportive care as aiming to improve quality of life, maximize function, and reduce complications, ideally through multidisciplinary care by specialists in relevant fields.

For SEGAs, GeneReviews describes mTOR inhibitor treatment as the primary medical therapy for growing or large SEGAs and for those causing mild-to-moderate symptoms, and describes urgent surgical treatment for SEGAs presenting with acute deterioration due to obstructive hydrocephalus. It cites the EXIST-1 clinical trial as finding that everolimus treatment resulted in a 30% reduction in SEGA volume in 65% to 79% of individuals, maintained for up to three years. GeneReviews characterizes infantile spasms as a neurologic emergency in infants with TSC requiring immediate evaluation and treatment.

FDA records in the packet list the following products with active market status: HYFTOR (sirolimus; approved 2022-03-22), EPIDIOLEX (cannabidiol; approved 2018-06-25), AFINITOR DISPERZ (everolimus; approved 2012-08-29), ZORTRESS (everolimus; approved 2010-04-20), and AFINITOR (everolimus; approved 2009-03-30). The packet's orphan drug records show indications for tuberous sclerosis complex for EPIDIOLEX and, for AFINITOR, for TSC-associated SEGA, angiomyolipoma, and LAM; indications for the other listed products are not itemized in the packet.

The packet also lists orphan drug designations for everolimus ointment, ganaxolone, rapamycin, sirolimus (two sponsors), and vigabatrin. An orphan designation does not indicate approval, efficacy, or active development.

GeneReviews states that CNS-related problems, including TAND, are the leading cause of morbidity in TSC, whereas kidney disease is the leading cause of mortality, and that TSC exhibits both inter- and intrafamilial variability. It reports that early recognition and control of seizures is highly correlated with improved developmental and neurologic outcomes in infants with TSC, and that optimal outcome in SEGAs is associated with early detection and treatment. Two thirds of individuals are reported to experience drug-resistant epilepsy. Life expectancy and survival figures are not certified in this packet.

ClinicalTrials.gov records in the packet include the following examples, listed by registry title; a title does not establish what an intervention achieves. NCT07680322 is a Phase 2 study of AV078 in participants with TSC refractory epilepsy (sponsor Aeovian Pharmaceuticals; not yet recruiting; beginning 2026-09-01). NCT02962414 is a Phase 3 roll-over study of long-term everolimus safety in patients with TSC and refractory seizures who completed the EXIST-3 study (sponsor Novartis; active, not recruiting). NCT07287202 is a Phase 1 study of SVG103 (paxalisib) in focal cortical dysplasia type II, TSC, or hemimegalencephaly (sponsor Sovargen; recruiting). NCT05044819 is a Phase 4 study assessing the potential for chronic liver injury in participants treated with Epidiolex oral solution (sponsor Jazz Pharmaceuticals; active, not recruiting). NCT02461459 concerns autism spectrum disorder and intellectual disability determinants in TSC (Boston Children's Hospital). Active clinical trials for this condition are listed on ClinicalTrials.gov.