Tuberous sclerosis complex is an autosomal-dominant, neurocutaneous, multisystem disorder characterized by cellular hyperplasia, tissue dysplasia, and multiple organ hamartomas.
The most commonly identified clinical presentations are epilepsy (infantile spasms), autism and cognitive impairment, and neonatal cardiac rhabdomyomas.
The primary recognized neurocutaneous features include dental pits, hypopigmented macules (ash leaf spots), facial angiofibromas, and ungual fibromas.
Cardiac rhabdomyomas regress in early childhood and are generally asymptomatic, whereas renal angiomyolipomas and giant cell astrocytomas progress in adolescence and adulthood. Renal complications are second only to central nervous system complications as a cause of significant morbidity.
Lymphangioleiomyomatosis of the lung associated with tuberous sclerosis is unique in that it is identified in females only and arises from metastases from renal angiomyolipomas.
The disease has two genetic loci: TSC1, found on chromosome 9q34; and TSC2, found on chromosome 16p13. The clinical phenotype can result from a mutation in either of these genes.
History and exam
Key diagnostic factors
- family history
- cardiac rhabdomyoma (single or multiple)
- renal angiomyolipomas
- lymphangioleiomyomatosis of the lung
- cerebral subependymal calcified nodules
- multiple cortical tubers and/or radial migration lines
- giant cell astrocytoma
- facial angiofibromas
- cephalic plaque(s)
- nontraumatic ungual or periungual fibromas
- hypomelanotic macules
- shagreen patch(es) (connective tissue nevus)
- retinal nodular hamartoma(s)
- polycystic kidney disease
Other diagnostic factors
- numerous dental enamel pits and intraoral fibromas
- cognitive impairment
- behavioral problems
- multiple hamartomatous colonic polyps
- genetic predisposition
Investigations to consider
- genetic testing
- brain MRI
- neurodevelopmental assessment
- electroencephalogram (EEG)
- abdominal MRI
- glomerular filtration rate (GFR)
- blood pressure
- high-resolution chest CT
- pulmonary function tests and 6-minute walk test
- skeletal x-ray
- renal biopsy
renal cell carcinoma (suspected or confirmed)
cognitive and behavioral
- Periventricular nodular heterotopia (PNH)
- Multiple endocrine neoplasia (MEN-1)
- Birt-Hogg-Dubé syndrome
- Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations
- The UK guidelines for management and surveillance of tuberous sclerosis complex
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