Schimmelpenning syndrome

Schimmelpenning-Feuerstein-Mims syndrome · linear naevus sebaceus syndrome · organoid naevus syndrome

Schimmelpenning syndrome is a mosaic neurocutaneous disorder defined by a large or linear naevus sebaceus with extracutaneous involvement of the central nervous system, eye and/or musculoskeletal system. Post-zygotic activating mutations in HRAS or KRAS underlie both the sebaceus naevus and the systemic features. Within the lesion, secondary tumours (most often trichoblastoma, syringocystadenoma papilliferum and, less commonly, BCC) may arise during adulthood.

CurrentLast reviewed 16 May 2026

Genetics and biology

Sporadic; mosaic post-zygotic activating mutations in HRAS (most commonly p.G13R) or less often KRAS.
Distribution follows lines of Blaschko, reflecting clonal proliferation from a mutant ectodermal precursor.
Germline mosaicism is generally absent; recurrence risk in offspring is very low.

Cutaneous features

Large or linear naevus sebaceus — yellowish, hairless, waxy plaque, often on scalp / face / neck; thickens at puberty.
Concomitant speckled lentiginous naevus, melanocytic naevi, aplasia cutis congenita may occur.
Secondary tumours within the naevus in adulthood: trichoblastoma (most common), syringocystadenoma papilliferum, trichilemmoma; BCC less common than historically reported (true BCC ~1-2%).

Extracutaneous features

CNS: cortical malformations (hemimegalencephaly), epilepsy (often pharmacoresistant), developmental delay, intellectual disability.
Ocular: epibulbar choristoma / dermoid, coloboma, microphthalmia, lipodermoid.
Musculoskeletal: bone hypertrophy / hypoplasia, vitamin-D-resistant rickets (FGF23-mediated), scoliosis.
Cardiac / renal: less common; coarctation, renal hypoplasia.

Diagnosis and surveillance

Clinical diagnosis. Brain MRI (any new neurological symptom or seizure); ophthalmologic review; spine and limb radiographs as indicated.
Skin biopsy of new nodules within naevus sebaceus to exclude secondary tumour.
Serum phosphate / FGF23 if rickets suspected.
Multidisciplinary clinical-genetics input where extracutaneous features are present; somatic / tissue-mosaicism testing on biopsy if molecular confirmation is needed.

Management

Excision of naevus sebaceus is no longer routinely recommended in childhood given low malignant transformation risk; consider for cosmetic, social or symptomatic indications.
Adult vigilance for new nodules — excise individual lesions arising within the naevus.
Anti-epileptic management; some refractory cases respond to MEK inhibitor trials (investigational; specialist neuro-oncology setting).
Vitamin-D / phosphate replacement if rickets; burosumab in selected cases (off-label).

References

Groesser L et al. Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. Nat Genet. 2012;44:783-787.

Happle R. Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol. 1993;129:1460-1470.

Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases. J Am Acad Dermatol. 2014;70:332-337.

Cribier B et al. Tumors arising in nevus sebaceus: a study of 596 cases. J Am Acad Dermatol. 2000;42:263-268.

Lim YH et al. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014;23:397-407.