The group of epidermal nevus syndromes: Part II. Less well defined phenotypes

doi:10.1016/j.jaad.2010.01.016

Journal of the American Academy of Dermatology

Volume 63, Issue 1, July 2010, Pages 25-30

https://doi.org/10.1016/j.jaad.2010.01.016 Get rights and content

In addition to the well established epidermal nevus syndromes, such as Schimmelpenning, Becker, Proteus, CHILD, or nevus comedonicus syndromes, the group of less well defined phenotypes associated with epidermal nevi presently includes nevus trichilemmocysticus syndrome, didymosis aplasticosebacea, SCALP syndrome (sebaceous nevus, central nervous system malformations, aplasia cutis congenita, limbal dermoid,and pigmented nevus), Gobello syndrome, Bäfverstedt syndrome, NEVADA syndrome (nevus epidermicus verrucosus with angio-dysplasia and aneurysms), and CLOVE syndrome (congenital lipomatous overgrowth, vascular malformations, and epidermal nevus). These syndromes can thus far be regarded as being in limbo. Future clinical and molecular research may show which of these disorders can be added to the list of well defined nosologic entities.

Learning objectives

After completing this learning activity, participants should be able to understand why the list of distinct epidermal nevus syndromes can thus far not be regarded as being complete; why clinicians, when seeing a patient with an epidermal nevus syndrome that is difficult to categorize, should bear in mind the group of less well defined epidermal nevus syndromes; and how practical dermatologists can help recognize rare forms of epidermal nevus syndromes and categorize them appropriately.

Section snippets

Nevus trichilemmocysticus syndrome

Key points

•
Nevus trichilemmocysticus is characterized by multiple trichilemmal cysts arranged along Blaschko's lines
•
Its cooccurrence with bone lesions may constitute a distinct syndrome

In 2007, nevus trichilemmocysticus was delineated as a distinct organoid nevus by Tantcheva-Poor et al.² The 31-year-old patient was cachectic and bedridden. She had systematized linear lesions covered with trichilemmal cysts (Fig 1, A), filiform hyperkeratoses, and comedo-like plugs. Severe osteomalacia, complicated by

Didymosis aplasticosebacea

Key points

•
Didymosis aplasticosebacea is characterized by a sebaceous nevus coexisting with aplasia cutis congenita
•
The two lesions usually occur in close proximity to each other
•
The disorder may be best explained as a further example of twin spotting

Didymosis aplasticosebacea is defined as a coexistence of aplasia cutis congenita and nevus sebaceus that are typically localized in close proximity to each other (Fig 2), which is why a twin-spot phenomenon has been assumed.³ In 2001, 16 cases were reviewed,³

Scalp syndrome

Key points

•
SCALP syndrome (sebaceous nevus, central nervous system [CNS] malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus) is a combination of didymosis aplasticosebacea with a large melanocytic nevus
•
Such cooccurrence has so far been described in three patients

Lam et al⁵ described a newborn with didymosis aplasticosebacea combined with a giant melanocytic nevus. They found two previous reports of such association6, 7 and proposed the acronym SCALP syndrome (sebaceous nevus, CNS

Gobello syndrome

Key point

•
A systematized, linear, velvety, orthokeratotic nevus showing hypertrichosis and follicular hyperkeratosis and being associated with multiple bone defects may represent a new entity

In 2000, an unusual disorder was described by Gobello et al.⁸ A 16-year-old boy had a systematized organoid nevus with velvety surface, increased hairiness, and follicular hyperkeratosis. The surrounding background skin showed a milder degree of follicular hyperkeratosis. Moreover, hemihypoplasia of limbs,

Bäfverstedt syndrome

Key points

•
Bäfverstedt syndrome is an unusual neurocutaneous phenotype
•
The disorder is characterized by horny excrescenes arranged in a linear pattern

In 1941, Bäfverstedt⁹ decribed an 18-year-old boy suffering from pronounced mental retardation, epileptic seizures, and an unusual hyperkeratotic disorder. At birth, a “rash in red blotches” was present and categorized as “milk eczema.” During childhood, innumerable horny excrescences developed on his face and neck and in the axillary regions, reaching a

Nevada syndrome

Key points

•
The term NEVADA syndrome has been proposed for a birth defect characterized by a hystrix-like epidermal nevus and multiple extracutaneous vascular malformations
•
The acronym NEVADA stands for nevus epidermicus verrucosus with angiodysplasia and aneurysms

The term NEVADA was proposed in 2003 as an acronym for nevus epidermicus verrucosus with angiodysplasia and aneurysms.¹¹ Affected children have a keratinocytic nevus of the orthokeratotic, nonepidermolytic category showing a bizarre, hystrix-like

Clove syndrome

Key points

•
The term CLOVE syndrome (congenital lipomatous overgrowth, vascular malformations, and epidermal nevus) was proposed for a phenotype to be separated from Proteus syndrome by the criterion of nonprogressive, proportionate overgrowth
•
The overgrown toes show “ballooning” rather than “distorting”

Among patients referred with a diagnosis of Proteus syndrome, Sapp et al¹⁷ separated seven cases that they no longer considered to meet the specific criteria of Proteus syndrome. They named the proposed new

Miscellaneous reports on birth defects coexisting with epidermal nevi

Kaur et al¹⁹ described a 17-year-old boy with a systematized, nonepidermolytic keratinocytic nevus, extrahepatic venous obstruction, and a hypoplastic kidney with lymphangiectasia.

The presence of a nonepidermolytic, nonorganoid EN was reported in three cases of McCune–Albright syndrome.20, 21, 22

Ment et al²³ noted cleft palate, patent ductus arteriosus, arrhinencephalia, and immunodeficiency in an infant who had, in addition, a linear pigmentary disorder and a flat keratinocytic nevus of the

Outlook

From this overview, it appears to be almost certain that the number of well established ENSs will increase in the near future. When clinicians see a patient with an ENS that is difficult to classify, they should bear in mind the present list of ENSs in limbo, from which new clearly defined entities may soon emerge.

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Syndromic vascular malformations related to the PIK3CA and RAS pathways: A clinical and imaging review
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Vascular malformations are a complex and diverse group of disorders. They may enlarge with time, impair quality of life, and even be fatal. While many are sporadic, others are part of inherited syndromes; several gene mutations responsible for vascular anomalies have been identified. The PI3K/AKT/mTOR and RAS/MEK/ERK cascades have been extensively studied, and new molecular agents targeting these cascades are being developed. Diagnostic imaging findings are increasingly used to guide genetic testing, and in some cases, pathognomonic imaging characteristics can lead to a specific diagnosis. We review each of the representative syndromes associated with PIK3CA and RAS cascades, with updates of the latest in clinical and imaging information.
Classification of and the latest photoelectric therapy for epidermal nevi
2022, Chinese Journal of Plastic and Reconstructive Surgery
An epidermal nevus (EN) is a common disease of various types, including verrucous EN, nevus sebaceous, inflammatory linear verrucous EN, Becker nevus, smooth muscle hamartoma, and nevus comedonicus. EN syndrome is a serious and difficult-to-treat syndrome that is complicated by two or more abnormal organs or systems. To date, the mechanism of an EN is still unclear, and the therapies remain unsatisfactory. The most frequently used treatments are surgery and laser therapy. Several drugs have also been tested. An EN requires more attention, and further research is needed to provide appropriate and effective treatments for each patient.
Hypertrichotic patches as a mosaic manifestation of Proteus syndrome
2021, Journal of the American Academy of Dermatology
Citation Excerpt :
The differential diagnosis for hypertrichosis overlying an epidermal nevus also includes Angora hair nevus syndrome, which is characterized dermatologically by long, soft, hypopigmented hair superimposed upon a blaschkoid epidermal nevus.15 There has also been a report of an individual with multiple skeletal defects and a linear epidermal nevus containing hypertrichosis and follicular hyperkeratosis,38 which may represent a newly described epidermal nevus syndrome.39 The pattern of hypertrichosis overlying a unilateral, overgrown limb is similar to that seen in congenital hemihypertrophy with hemihypertrichosis, which has been reported in 3 neonates with hypertrichosis overlying an overgrown arm and leg.16-18
Proteus syndrome is an overgrowth disorder caused by a mosaic activating AKT1 variant. Hair abnormalities in Proteus syndrome have rarely been reported, and frequencies of such findings have not been elucidated.
To define the types and frequencies of hair findings in individuals with Proteus syndrome.
A cross-sectional study was conducted of individuals with clinical features of Proteus syndrome and a confirmed pathogenic variant in AKT1 evaluated between November 1996 and June 2019 at the National Institutes of Health Clinical Center. Medical records were reviewed for patterning, density, and color of hair on the body and scalp.
Of 45 individuals evaluated, 29 (64%) had asymmetric hypertrichosis on the body. This included unilateral blaschkoid hypertrichotic patches overlying normal skin or epidermal nevi in 16 (36%), unilateral nonblaschkoid hypertrichotic patches in 11 (24%), and unilateral limb hypertrichosis in 10 (22%). Diffuse, scattered, or patchy changes in scalp hair density or color were present in 11 individuals (24%).
The retrospective, observational design, and limited longitudinal follow-up.
Asymmetric variations in hair distribution, thickness, length, and color contribute to the overall mosaic appearance of the skin in Proteus syndrome, an observation that provides novel insights into the role of phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling in skin appendage development.
Multiple adenomatoid odontogenic tumors in a patient with Schimmelpenning syndrome
2020, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Citation Excerpt :
Phacomatosis pigmentokeratotica (PPK), nevus comedonicus syndrome, Becker nevus syndrome, Proteus syndrome, and CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome are some of the well-defined phenotypes of ENS conditions.5 ENS also comprises several less-defined phenotypes, such as nevus trichilemmocysticus syndrome, didymosis aplasticosebacea, scalp syndrome, and Gobello syndrome.20 The differential diagnosis of SS includes PPK, nevus comedonicus syndrome, and Proteus syndrome.5
Schimmelpenning syndrome (SS) is a congenital neurocutaneous disorder characterized by the presence of linear nevus sebaceous, ophthalmic, neurologic, skeletal, urologic, and cardiovascular alterations. Oral manifestations related to SS mainly include dental defects, papillary lesions in the oral mucosa, giant cell lesions of the jaws, and odontogenic tumors. Here, we report the first case of multiple adenomatoid odontogenic tumor observed in a patient with SS.
Epidermal Nevi and Related Syndromes –– Part 1: Keratinocytic Nevi
2018, Actas Dermo-Sifiliograficas
Los nevus epidérmicos son hamartomas originados en la epidermis y/o en las estructuras anexiales de la piel que se han clasificado clásicamente partiendo de la morfología. En los últimos años se han descrito variantes nuevas y se han producido avances en el campo de la genética que han permitido caracterizar mejor estas lesiones y comprender su relación con algunas de las manifestaciones extracutáneas a las que se han asociado. En esta primera parte revisaremos los nevus derivados de la epidermis y los síndromes que se han descrito asociados a ellos.
Epidermal nevi are hamartomatous lesions derived from the epidermis and/or adnexal structures of the skin; they have traditionally been classified according to their morphology. New variants have been described in recent years and advances in genetics have contributed to better characterization of these lesions and an improved understanding of their relationship with certain extracutaneous manifestations. In the first part of this review article, we will look at nevi derived specifically from the epidermis and associated syndromes.
Generalised keratinocytic epidermal nevi
2018, Anales de Pediatria

View all citing articles on Scopus

: Funding sources: None.

: Conflicts of interest: The authors, editors, JAAD CME council members, and peer reviewers have no relevant financial relationships.

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Continuing medical educationThe group of epidermal nevus syndromes: Part II. Less well defined phenotypes

Learning objectives

Section snippets

Nevus trichilemmocysticus syndrome

Didymosis aplasticosebacea

Scalp syndrome

Gobello syndrome

Bäfverstedt syndrome

Nevada syndrome

Clove syndrome

Miscellaneous reports on birth defects coexisting with epidermal nevi

Outlook

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Am J Ophthalmol

J Am Acad Dermatol

Neurologic Clinics

J Am Acad Dermatol

Didymosis aplasticosebacea: coexistence of aplasia cutis congenita and nevus sebaceus may be explained as a twin spot phenomenon

Dermatology

Epidermal nevus syndrome and didymosis aplasticosebacea

Pediatr Dermatol

Jadassohn-Schimmelpenning-Feuerstein-Mims-Syndrom (Naevus-sebaceus-linearis-Syndrom)

Akt Dermatol

Multiple hamartomas associated with intracranial malformation

Pediatr Dermatol

New type of epidermal nevus syndrome

Dermatology

Fall von genereller, naevusartiger Hyperkeratose, Imbecillität, Epilepsie

Acta Derm Venereol

Vitamin A in the treatment of maleformatio ectodermalis generalisata—“porcupine man”

Acta Derm Venereol

Cutaneous mosaicism

Ein Solitärfall von Ichthyosis hystrix gravior unilateralis: klinische und morphologische Befunde

Z Hautkr

Linear sebaceous nevus syndrome in a newborn

Am J Dis Child

Linear epidermal nevus with multiple malformations (“epidermal nevus syndrome” of Solomon) [in German]

Klin Pädiatr

Neurological involvement in the epidermal naevus syndrome

J Neurol Neurosurg Psychiatry

Continuing medical education
The group of epidermal nevus syndromes: Part II. Less well defined phenotypes