In 1895, Kofmann described the first case of nevus comedonicus. It manifests as groups of closely set, dilated follicular openings with dark keratin plugs resembling comedones. The majority of cases are isolated. However, nevus comedonicus may be part of nevus comedonicus syndrome in association with skeletal or central nervous system anomalies, ocular abnormalities, and cutaneous defects.
Epidermal nevi (EN) are congenital hamartomas of embryonal ectodermal origin classified on the basis of their main component; the component may be sebaceous, apocrine, eccrine, follicular, or keratinocytic. An estimated one third of individuals with epidermal nevi have involvement of other organ systems; hence, this condition is considered to be an epidermal nevus syndrome (ENS). Solomon defines epidermal nevus syndrome as a sporadic neurocutaneous linkage of congenital ectodermal defects in the skin, brain, eyes, and/or skeleton. Epidermal nevus syndrome is often termed the Solomon syndrome. Schimmelpenning first detailed epidermal nevi with neurologic anomalies; hence, the term Schimmelpenning syndrome. The term organoid nevus may be used to emphasize the admixture of epidermal cells often evident in individual lesions of epidermal nevi.
Gustav Schimmelpenning, born in 1928 in Oldenburg (Germany), served from 1971-1994 as the head of the Department of Psychiatry at the University of Kiel. In 1957, he described a case of sebaceous nevus involving the head, with ipsilateral ocular lesions including coloboma of the upper lid, increased density of cranial bones, epileptic seizures, and mental retardation. He called this combination of anomalies a new phacomatosis. Subsequently, others reported this phenotype as Schimmelpenning syndrome, Feuerstein-Mims syndrome, Schimmelpenning-Feuerstein-Mims syndrome, epidermal nevus syndrome, Solomon syndrome, linear sebaceous nevus (LSN) syndrome, organoid nevus phacomatosis, or Jadassohn nevus phacomatosis.
A clinical entity called epidermal nevus syndrome should be more precisely defined and distinguished by clinical, histopathologic, and genetic criteria. In this review, 4 distinct epidermal nevus syndromes, recognizable by the different types of associated epithelial nevi, are described. These include linear sebaceous nevus, linear nevus comedonicus (NC), linear epidermal nevus (LEN), and inflammatory linear verrucous epidermal nevus (ILVEN). Each type may be regarded as part of a syndrome with systemic associations.
Linear epidermal nevus syndrome is a congenital neurocutaneous disorder characterized by linear epidermal nevus with significant involvement of the nervous, ophthalmologic, and/or skeletal systems. Clinical manifestations include mental retardation, seizures, and movement disorders that are caused by a wide range of neuropathologic lesions. Intracranial and/or intraspinal lipomas may occur.
Linear sebaceous nevus, also known as organoid nevus syndrome, often has the term linear deleted because almost all syndromic sebaceous nevi are linear. It has also been called Schimmelpenning-Feuerstein-Mims syndrome and Jadassohn nevus phakomatosis. Schimmelpenning syndrome, as noted above, links a sebaceous nevus with cerebral anomalies, coloboma, and lipodermoid of the conjunctiva.
Linear nevus comedonicus is also known as comedone nevus, nevus follicularis keratosus, nevus acneiformis unilateralis, and nevus zoniform. Cataracts may be a prominent feature of nevus comedonicus syndrome.
Inflammatory linear verrucous epidermal nevus is a linear, persistent, pruritic plaque, usually first noted on a limb in early childhood. Originally described by Unna in 1896, a few patients were reported prior to 1971 when Altman and Mehregan delineated inflammatory linear verrucous epidermal nevus as a distinct entity in 25 patients. They coined the name inflammatory linear verrucous epidermal nevus, labeling it a clinical and histopathologic type of linear verrucous nevus that is often inflammatory or psoriasiform. Inflammatory linear verrucous epidermal nevus accounts for approximately 5% of patients with epidermal nevi and has been described in a mother and daughter.
Six different syndromes with epidermal nevi as part of them have been delineated. These include (1) Proteus, (2) congenital hemidysplasia with ichthyosiform nevus and limb defect, (3) phakomatosis pigmentokeratotica, (4) sebaceous nevus, (5) Becker nevus, and (6) nevus comedonicus syndromes.
Phacomatosis pigmentokeratotica is characterized by the presence of multiple organoid nevi with sebaceous differentiation, a speckled lentiginous nevus, and skeletal and neurologic abnormalities. It may or may not be associated with extracutaneous involvement. In a study of one affected family, phacomatosis pigmentokeratotica was found to be caused by a postzygotic HRAS mutation in a multipotent progenitor cell.
The spectrum has recently been expanded with the description of linear Cowden nevus as a new distinct epidermal nevus. This nonorganoid epidermal nevus is probably due to loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. The combination of nevoid hypertrichosis, diffuse lipoatrophy, and epidermal nevus has been suggested as a possible new epidermal nevus syndrome.