Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic neurocutaneous disorder first described in 1970 by Haberland and Perou, also referred to as Haberland syndrome.1,2,11 ECCL is a tumor predisposition syndrome, included in the oculoectodermal syndrome (OES) heterogeneous group of mosaic RASopathies.4

ECCL primarily affects the skin, central nervous system (CNS), and eyes. Key diagnostic features include nevus psiloliparus (NP), a hallmark subcutaneous lipomatous hamartoma associated with alopecia, seen in approximately 75 % of cases, along with subcutaneous lipomas, focal skin aplasia, and patchy alopecia. Neurologically, intracranial lipomas, particularly in the cerebellopontine angle, are prevalent, along with cortical dysplasia, ventriculomegaly, and vascular malformations. Ocular findings commonly involve choristomas, lipodermoids, and dermoids, which may impair vision. Most findings are present at the time of birth and vary widely between patients.11

Genetic analysis has identified postzygotic (mosaic) pathogenic variants in FGFR1 or KRAS genes, supporting the hypothesis of somatic mosaicism. Molecular testing aids diagnosis but is not always conclusive.

Males and females are equally affected, with no known associations to geographic or ethnic backgrounds. To date, no recurrence has been observed in siblings or offspring.11

Management is multidisciplinary, involving dermatological, neurological, and ophthalmologic evaluations. Brain and spine MRI can be considered depending on the clinical context for regular surveillance. Treatment focuses on symptomatic care, including anti-seizure medications for epilepsy, surgical management of tumors, and supportive therapies for developmental delays. The prognosis varies, with most individuals leading generally normal lives, though there is a risk of developmental delay, seizures, and an increased risk of low-grade gliomas. The severity of CNS involvement does not consistently correlate with cutaneous or ocular abnormalities.