Synonyms: Schimmelpenning's syndrome, Schimmelpenning-Feuerstein-Mims' syndrome, Feuerstein-Mims' syndrome, Solomon's syndrome, linear sebaceous naevus syndrome, organoid naevus phacomatosis, Jadassohn's naevus phacomatosis, naevus sebaceous of Jadassohn.

Note that these synonyms are used variably (see subsets of ENS below).

See also: Epidermal Naevus, Sebaceous Naevus

Definition¹

Epidermal naevus syndromes (ENS) are a heterogenous group of disorders characterised by the presence of:

• One or more congenital hamartomatous ectodermal naevi of the skin
• Other organ involvement, commonly:
  • The brain
  • The eye
  • The skeleton

There are various subsets of ENS, and some recognised syndromes, which are detailed below.

A hamartoma is defined as a focal growth that resembles a neoplasm but results from faulty development in an organ.² There is no standard definition of the term 'naevus', but the following definition has been proposed: "Naevi are visible, circumscribed, long-lasting lesions of the skin or the neighbouring mucosa, reflecting genetic mosaicism".³

Aetiology⁴

The lesions probably arise from abnormal ectodermal cells in the embryo. Ectodermal cells give rise to the skin epidermis and to neural tissue. Mosaicism seems to be involved, i.e. there are genetically different cell lines in one individual, and the abnormal cells give rise to the lesions.

Epidermal naevi follow the lines of Blaschko, which are the tracks of genetically identical cells in the developing embryo.

A detailed review of the genetic basis and pathogenesis of ENS is available.¹

Epidemiology

They are all very uncommon syndromes, without reliable population incidence figures. Epidermal naevi (with or without other organ involvement) have an incidence of around 2 per 1,000 live births.¹ Of patients with epidermal naevi, 10-30% may have disorders in other organs suggesting an ENS.⁵

Clinical features - overview¹

Skin lesions:

• The epidermal naevus is a patch or plaque of overgrown abnormal skin. It is usually present from birth or shortly thereafter, but may not be noticed until puberty.
• The lesions generally follow Blaschko's lines (purported embryonic lines of ectodermal cleavage).^4,6
• The lesions themselves are usually asymptomatic apart from their appearance. However, inflammatory linear verrucous epidermal naevus (ILVEN) lesions (see below) may be inflamed and irritated; naevus comedonicus lesions may become infected or inflamed.

Neurological involvement includes:

• Epilepsy or infantile spasms
• Intellectual impairment
• Structural or vascular brain abnormalities
• Spinal lesions⁷

Skeletal involvement includes:

• Incomplete formation of bony structures
• Hypoplasia of bones
• Bony cysts
• Asymmetry of skull or spine
• Spontaneous fractures and rickets

Ophthalmic involvement includes:

• Colobomas
• Strabismus
• Corneal opacities
• Retinal changes
• Various other ocular abnormalities have been described

Endocrine features have been reported:

• Hypophosphataemic vitamin D-resistant rickets has occurred in a number of cases⁸
• Precocious puberty has been described in several cases
• Syndrome of inappropriate anti-diuretic hormone (SIADH) has been reported in one case

Subtypes of epidermal naevus syndromes ¹

Note on terminology: various different classifications and subsets of ENS have been denoted by different authors. The list below is based on the recent review by Sugarman.¹ Some authors have used different terms, either for ENS as a group, or for one of its subsets. For example, 'linear naevus sebaceous syndrome' has been used to refer to ENS as a whole or to a subset.⁹ The synonyms of ENS (listed above) are also used in varying ways.¹⁰

Naevus sebaceous

• Relatively common among ENS.
• Skin lesions are salmon or yellow colour and waxy.
• Epilepsy and intellectual impairment are common.

Keratinocytic epidermal naevus

• Again, relatively common.
• Pink or hyperpigmented plaques.
• Intellectual impairment, structural brain abnormalities, skeletal abnormalities and strabismus are reported.

Naevus comedonicus

• Skin lesions are localised collections of dilated follicles containing keratin, which may become infected or inflamed.
• EEG abnormalities, cataracts and skeletal abnormalities are reported.

Congenital hemidysplasia, ichthyosiform naevus and limb defects syndrome

Synonym: congenital unilateral ichthyosiform erythroderma.

• CHILD is the acronym for Congenital Hemidysplasia, Ichthyosiform Naevus and Limb Defects.
• Skin lesions are unilateral inflammatory, reddened patches which may have dry scales; often located in the skinfolds.
• Ipsilateral hypoplasia of limbs can occur; the axial skeleton may also be affected.
• EEG abnormalities and hemispheric brain hypoplasia and cardiac abnormalities are reported.

Becker naevus (pigmented hairy epidermal naevus)

• A patch of hyperpigmentation and hypertrichosis, which is androgen-dependent and so becomes more prominent after puberty in males; usually located on the shoulder.
• Onset is usually in late childhood/adolescence.
• Associated with skeletal abnormalities, underlying muscle hypoplasia and ipsilateral hypoplasia of the breast.

Proteus syndrome

• Variable clinical features, characterised by overgrowth of multiple tissues.
• CNS involvement is not typical, but seizures and intellectual impairment have been reported.
• Other possible features are ovarian or parotid tumours, lipomas and vascular malformations.
• There are diagnostic criteria.

Phacomatosis pigmentokeratotica

• A speckled-lentiginous naevus associated with an epidermal naevus. The melanocytic component usually follows a segmental pattern ('checkerboard pattern') rather than following the lines of Blaschko.
• There may be neurological, ocular and skeletal abnormalities.
• Hemiatrophy with muscle weakness is common.

Inflammatory linear verrucous epidermal naevus

• Skin lesions are linear, pruritic, reddened and hyperkeratotic papules or plaques.
• Usually unilateral on the lower half of the body, often the buttock.
• Often presents < 6 months of age.
• May resemble psoriasis.
• There may be associated skeletal abnormalities, although this point has been questioned.

Porokeratotic eccrine naevus

• Verrucous, keratotic papules on palms and soles.
• There may be widespread cutaneous involvement.

Assessment

Initial assessment:¹

• Full developmental and family history.
• Careful examination of all skin lesions. Skin biopsy may be required.
• Neurological examination.
• Ophthalmic examination.
• Assess skeleton, symmetry and gait.

Consider if further assessment required:

• Generally, children with small epidermal naevi and no other findings do not need further investigation, although skin biopsy should be considered.¹
• Large epidermal naevi, especially in the head and neck, may merit CNS assessment.⁷
• Epidermal naevi should be fully assessed if there is a suspected syndrome involving other organs.

Further assessment:¹

• Further evaluation of neurology, eye or skeleton if appropriate.
• Investigations (below).
• If there are no neurological findings, follow-up until school age is probably sufficient.

Investigations¹

These should be individualised (see assessment and management, below) but may include:

• Skin lesions should be referred for dermatological assessment and/or biopsied to ascertain their nature.
• CT/MRI are used to assess the presence/degree of any intracerebral or intraspinal lesion.
• Plain x-rays e.g. skull x-ray, chest x-ray or skeletal survey.
• EEG.
• Biochemistry and endocrine investigations may be appropriate, e.g. renal function, electrolytes, calcium and phosphate.

Differential diagnosis⁷

• Uncomplicated dermatological epidermal naevus or sebaceous naevus
• Other skin and CNS lesions, e.g:
  • Sturge-Weber syndrome
  • Tuberous sclerosis
  • Neurofibromatosis
  • McCune-Albright syndrome

Management¹

This should be individualised and may involve various specialities, e.g. dermatology, paediatric neurology, ophthalmology, orthopaedics, plastic surgery and psychology.

Management of the skin lesion(s):

• Depending on the location and size of the lesions, excision may be merited for cosmetic reasons, but may not be feasible if underlying structures are involved.
• Other possible treatments are:
  • Laser treatment may be successful in some cases.
  • Topical vitamin D (calcipotriol) may be helpful in treating ILVEN, though there is conflicting evidence about its effectiveness.
  • 5-fluorouracil was used with good results in one case of a large linear epidermal naevus.
  • Tacrolimus and fluocinonide in combination, were successfully used in one case of ILVEN.¹¹
  • Shave excision followed by phenol peeling was used with good outcome in one case of verrucous epidermal naevus.
• If there is new growth of the skin lesion, excisional biopsy may be indicated to rule out malignancy.

CNS lesions:

• Anticonvulsants for epilepsy.
• Neurosurgery has been used in a few selected cases to control epilepsy.¹²

Genetic counselling:

• In certain cases, referral to a geneticist may be relevant to assess the possibility of transmitting a more generalised (related) disease, e.g. Apert's syndrome.

Complications

• Skin cancers:
  • Some cases of skin malignancies have been reported with sebaceous naevi.¹³ These include basal cell carcinoma, squamous cell carcinoma and cancers of the skin adnexae. However, recently the extent of the cancer risk in epidermal naevi has been questioned, and it is suggested that some lesions may have been misdiagnosed in the past.¹
• Other complications depend on the nature, size and site of the lesions, but can include:
  • Neurological dysfunction, intellectual impairment or epilepsy
  • Ocular and oculomotor dysfunction
  • Skeletal deformity
  • Inflammation and irritation within the skin lesion (ILVEN syndrome or naevus comedonicus)
  • Endocrine abnormalities (as above)

Prognosis

• Prognosis for the skin lesion is usually good, although some lesions enlarge during puberty.
• Prognosis of other symptoms is variable, depending on the nature and extent of other organ involvement.