Tuberous Sclerosis Skin Features
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Direct answer
Tuberous sclerosis complex is an autosomal dominant hamartoma syndrome caused by TSC1 or TSC2 mutations, and its skin features are often the first clue to diagnosis. Ash-leaf macules, facial angiofibromas, shagreen patches and periungual fibromas (Koenen tumours) form the cutaneous core of the disease. Diagnosis rests on the revised clinical criteria, and topical sirolimus, an mTOR inhibitor, is used for facial angiofibromas.
What you must remember
- Genes: TSC1 on chromosome 9q34 (hamartin) and TSC2 on chromosome 16p13.3 (tuberin); both restrain mTORC1 signalling.
- Ash-leaf macules: oval hypomelanotic macules, often the earliest sign, best seen under Wood lamp; three or more count as a major criterion.
- Facial angiofibromas: firm pink papules on the nose and cheeks that appear in childhood; the older name adenoma sebaceum is still used in exams.
- Shagreen patch: a connective tissue naevus, a leathery orange-peel plaque typically over the lumbosacral region.
- Koenen tumours: periungual or subungual fibromas, a major criterion when present.
- Forehead plaque: a fibrous cephalic plaque, a major criterion; confetti lesions are a minor criterion.
- Other organs: cortical tubers, subependymal nodules, renal angiomyolipomas and cardiac rhabdomyomas; seizures and autism are common.
Skin signs by onset and diagnostic weight
Skin signs appear at different ages, and several of them carry weight in the diagnostic criteria. The table lists the main signs in the usual order of appearance. Noting the age of onset helps place a lesion in the sequence.
| Skin sign | Typical appearance | Usual onset | Criteria weight |
|---|---|---|---|
| Ash-leaf macules | Oval hypopigmented patches, bright under Wood lamp | Infancy | Major if three or more |
| Facial angiofibromas | Pink to red papules on nose and cheeks | Childhood | Major |
| Shagreen patch | Leathery orange-peel plaque, lumbosacral | Childhood | Major |
| Ungual fibromas | Fleshy nodules at the nail folds | Adolescence | Major |
| Confetti lesions | Multiple small hypopigmented macules | Childhood onward | Minor |
Ash-leaf macules are often the earliest sign, so a Wood lamp check is useful in infants with seizures. Under the revised criteria, two major features, or one major with two minor features, give a definite diagnosis. Because each sign carries a different weight, the count of major and minor features matters more than any single lesion.
Where the skin signs mislead in exams
Exam questions on tuberous sclerosis often pivot on mimics or on the criteria count.
- Trap: calling every hypopigmented macule an ash-leaf macule. Correct: ash-leaf macules are oval and hypomelanotic, while pityriasis alba and vitiligo look less defined.
- Trap: attributing facial papules to acne. Correct: facial angiofibromas are firm, non-comedonal papules that appear in childhood.
- Trap: treating facial angiofibromas with antibiotics. Correct: topical sirolimus or laser treatment is used, and antibiotics have no role.
- Trap: assuming one shagreen patch confirms the disease. Correct: a single major feature is insufficient; the diagnosis needs two major features or one major with two minor features.
Frequently asked questions
Which skin sign is often the earliest in tuberous sclerosis complex?
Ash-leaf macules are often the earliest skin sign in tuberous sclerosis complex and may be visible only under Wood lamp in infancy. Their presence in an infant with seizures should prompt a full evaluation.
What are Koenen tumours?
Koenen tumours are periungual or subungual fibromas that appear in adolescence in tuberous sclerosis complex. They count as a major diagnostic criterion when present and are often seen alongside facial angiofibromas.
How many major features give a definite diagnosis of tuberous sclerosis?
Under the revised criteria, two major features, or one major feature with two minor features, give a definite diagnosis of tuberous sclerosis complex. A pathogenic TSC1 or TSC2 variant alone also gives a definite diagnosis, so genetic testing helps when clinical criteria are equivocal.
Which drug treats facial angiofibromas in tuberous sclerosis?
Topical sirolimus, an mTOR inhibitor, is used for facial angiofibromas in tuberous sclerosis complex and reduces lesion size. Laser treatment is an alternative, while oral mTOR inhibitors are reserved for systemic disease such as subependymal giant cell astrocytoma.
Which systemic lesions matter most in tuberous sclerosis complex?
Subependymal giant cell astrocytoma, renal angiomyolipomas, cardiac rhabdomyomas and lymphangioleiomyomatosis are the major systemic lesions in tuberous sclerosis complex. Seizures and intellectual disability are the most common neurological problems.