Abstract
Epidermal nevus syndrome (ENS) encompasses a group of congenital genetic disorders
characterized by the association of an epidermal nevus with systemic anomalies including
the brain. The most frequent subtype with neurological features is linear sebaceous nevus syndrome (LSNS), followed by keratinocytic nevus syndrome (ENS). Both are caused by postzygotic
RAS mutations. All forms of ENS are mosaic disorders that share a common embryological
basis and pathogenesis as neurocristopathies. The lines of Blaschko indicate the cutaneous migratory pathways of neural crest.
Neural crest defects explain the development of nevi and associated multisystemic
anomalies: brain, ocular, osseous, muscular, orodental, cardiovascular, endocrine,
renal/urinary, and adipose tissue. Epilepsy and cognitive and motor deficits are caused
mainly by hemimegalencephaly (HME), a closely related mosaic anomaly caused by somatic
mutations in PI3K–AKT3–mTOR pathway that determines overgrowth. The usual onset of
epilepsy is in the neonatal period or early infancy, often as infantile spasms. The
pioneer description of nevus sebaceous in 1895 by Jadassohn is the basis for delineating
the LSNS. The eponym “Schimmelpenning syndrome” as a substitute for that long-established
term makes no sense in the context of the large number of authors who contributed
to defining this syndrome. A review of 111 cases of LSNS and other subtypes enabled
a classification of neurological phenotypes; epilepsy occurred in 77% and HME in 38%.
Three distinctive additional syndromes also are within the spectrum of ENS: CLOVES,
SCALP, and Heide's syndrome. The impact of epilepsy in patients affected by ENS is
related to time of onset and extent of brain anomalies. Timing of the mutation determines
the phenotype and severity of the systemic lesions.
Keywords
hemimegalencephaly - neurocristopathy - keratinocytic nevus syndrome - linear sebaceous
nevus syndrome - CLOVES syndrome - Heide's syndrome - congenital hemifacial hyperplasia
with lipomatosis - timing
