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Epidermal nevus syndrome associated with polyostotic fibrous dysplasia, CNS lipoma, and aplasia cutis

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Epidermal nevus syndrome associated with polyostotic fibrous dysplasia, CNS lipoma, and aplasia cutis
Miguel Cabanillas MD1, Ángel Aneiros MD2, Benigno Monteagudo MD1, Diego Santos-García PhD2, Oscar Suárez-Amor MD1, Aquilina Ramírez-Santos MD1
Dermatology Online Journal 15 (10): 7

1. Department of Dermatology, Complexo Hospitalario Arquitecto Marcide-Novoa Santos, Ferrol, Spain.
2. Department of Neurology, Complexo Hospitalario Arquitecto Marcide-Novoa Santos, Ferrol, Spain.


Epidermal nevus syndrome is a rare congenital sporadic neurocutaneous disorder characterized by an epidermal nevus and various developmental abnormalities of the skin, eyes, nervous, cardiovascular and urogenital systems. We describe a patient with an extensive epidermal nevus associated with various organ abnormalities, particularly polyostotic fibrous dysplasia, central nervous system lipoma, and aplasia cutis. Our patient demonstrates the polymorphic spectrum of involvement in epidermal nevus syndrome.


Epidermal nevus syndrome (ENS) is characterized by epidermal nevi together with abnormalities in other organ systems, most commonly the central nervous system (CNS) and skeleton. Polyostotic fibrous dysplasia (PFD) is an uncommon skeletal condition with multifocal abnormality of bone growth and progressive sclerosis that favors pathological fractures. It has been classically associated with Mc Cune-Albright syndrome. Central nervous system is a rare location for lipomas and this feature is often linked to hamartomatosis, such ENS. Congenital aplasia cutis is an abnormality in skin development usually involving the scalp.

We report a case of ENS with a wide spectrum of cutaneous, neurological and skeletal abnormalities demonstrating the polymorphic and multisystemic presentation of this condition. The anatomical localization of skin and skeletal lesions in our patient can suggest clues about the etiopathogenesis of the disease.

Case report

A 26-year-old man was referred to our clinic from the neurology department for assessment of cutaneous lesions. He had been diagnosed with neurofibromatosis type 1 at the age of 3 because of his many hyperchromic cutaneous lesions on the left side of his body. He had suffered many pathological fractures in his left leg, arm, and ribs. His left lower limb was shortened and deformed after multiple surgical postraumatic procedures. Neurological examination was abnormal; he exhibited nystagmus, right Babinski sign, and right rotulian hyporeflexia. Cognitive function was completely preserved.

Figure 1Figure 2
Figure 1. Unilateral verrucous brown plaques distributed in a blaschkolinear pattern, involving left trunk and left upper limb.

Figure 2. Focal skin defect in cranial vertex

Skin examination revealed multiple verrucous, brown, linear papules and plaques involving the left side of the trunk and upper limb, following Blaschko lines (Fig. 1). He also exhibited a congenital cutaneous defect with alopecia of the scalp vertex (Fig. 2), suggesting the diagnosis of aplasia cutis. Skin biopsy of a linear plaque was performed, showing hyperkeratosis with orthokeratosis, acanthosis, and papillomatosis with mild hyperpigmentation of the basal layer without melanocytic hyperplasia (Fig. 3). These changes confirmed the clinical hypothesis of epidermal nevus. Because lesions were asymptomatic no treatment was prescribed.

Figure 3Figure 4
Figure 3. Hyperkeratosis orthokeratotica, acanthosis, and papillomatosis with slight hyperpigmentation of basal layer

Figure 4. T1 hyperintense right-posterior intradural mass from T2-T8, with slight compression of spinal cord

Figure 5
Figure 5. Abnormalities of bony texture with radiolucent areas involving left pelvis and femur

Magnetic resonance imaging of CNS revealed a right-posterior lipoma in the spinal canal from T2-T8, with slight compression of spinal cord (Fig. 4). Skeletal radiographs revealed typical lesions of polyostotic fibrous dysplasia, which were confined to the left side of the body, involving particularly left pelvis, femur (Fig. 5), and also some left ribs. Laboratory studies including serum levels of calcium, phosphate, 1-25 dihydroxycholecalciferol, parathyroid hormone and alkaline phosphatase showed no abnormalities. The patient was referred for ophthalmological evaluation and audiometric testing, but no abnormalities were found. The patient is being followed in the departments of neurology, neurosurgery, rheumatology and dermatology of our hospital in order to manage the potential complications of his condition.


Epidermal nevus syndrome (ENS) is a term first used by Solomon et al. [1] to describe the occurrence of epidermal nevi combined with different extracutaneous organ disturbances. The majority of extracutaneous manifestations involve the brain, eye, and skeletal system. Although many continue to use this term, it is now understood that this is not one disease, but rather a heterogeneous group, each with a different genetic profile but a common phenotype: epidermal and adnexal hamartomas associated with other organ system involvement. Several subsets with characteristic findings have been described, including the nevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, Becker nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica [2].

Skeletal abnormalities in ENS are common, ranging from 50 percent to 66 percent of patients. Primary osseus changes include hypertrophy or hypoplasia of bones and bone cysts, syndactilia, aplasia of the ribs, assymetry of the skull and facial hemihypertrophy. Secondary bone changes include kyphoscoliosis and limb hypertrophy [3]. Vitamin-D resistant rickets associated with ENS has also been reported, affecting as much as 8.5 percent of patients with ENS in a larger series [4]. It is probably the result of the action of a phosphaturic factor produced by the nevus or other associated tumors such as hemangiomas [5, 6].

Polyostotic fibrous dysplasia has been rarely described in association with ENS [7, 8, 9, 10], usually involving bones located ipsilateral to the skin findings, as in our patient. This disorder is thought to represent an abnormality of bone growth such that spicules of bone and islands of cartilage are interspaced in a matrix of collagenous tissue. It usually affects one side of the body, with the femur, ilium tibia, pubis, humerus, radius, scapula, and clavicle being involved in that order. Bone pain, pathological fractures, and deformities secondary to bowing or swelling of a bone are the most frequent clinical presentations in these patients. Radiologically there may be expansile lesions, thickening of the cortex, trabeculation of the bone (varying from radiolucent areas to an uniform "ground glass" appearance), sclerosis, and deformities of the bone. Interestingly, ENS has been reported with focal skeletal-associated disease and diffuse osteopenia with hypophosphatemic rickets, showing radiological and histopathological changes in focal bone disease different from classic fibrous dysplasia. The authors suggested that elevated circulating level of fibroblast growth factor 23 produced by involved bone could function as a "phosphatonin," inducing the hypophosphatemic rickets [11].

Central nervous system involvement in ENS is estimated to occur in 50 percent to 70 percent of patients. Central nervous system manifestations of ENS are similar to those of other neurocutaneous syndromes, such as neurofibromatosis type 1 (NF-1) and encephalocraniocutaneous lipomatosis (ECCL). The latter is characterized by cutaneous lipomatosis usually involving the skull, eye, viscera, and the nervous system, often associated with other ipsilateral pathological findings of the CNS (micropolygyria, congenital mantle defect, porencephaly, cerebral calcifications and glial heterotopias).

Seizures and mental retardation are the most common neurological abnormalities in ENS. Other neurologic manifestations reported include hypotonia, hyperkinesia, hemiparesis, hemiplegia, cranial nerve palsies, hydrocephalus, hemimegalencephaly, cortical lesions, cortical atrophy, ventricular abnormalities and intracerebral calcification.

Central nervous system lipomas have been scarcely reported in ENS [12, 13, 14]. Most cases were located in the spinal canal, as in our case, but intracranial involvement, particularly of the cerebellopontine angle [12, 14] has also been described. In one case, the intraspinal lipoma was connected through the vertebral foramen to a superficial neck lipoma [12]. Central nervous system lipomas are a typical feature of ECCL and the occurrence of these lesions in ENS demonstrates the considerable clinical overlap between different neurocutaneous syndromes, probably because they share similar chromosomal aberrations. Clinical manifestations of CNS lipomas are usually caused by compression of nearby structures, such as spinal cord, nerve roots, cerebellum, or brain stem. The symptoms include hyperreflexia, hypertonia, and other neuromotor symptons. However, sometimes CNS lipomas represent an incidental finding in a study performed for any other reason, so MRI is recommended even in asymptomatic ENS patients in order to rule out subtle associated abnormalities.

Aplasia cutis congenital (ACC) is a cutaneous defect usually involving the midline of scalp, but virtually any site of the body can be afected by this developmental abnormality. It can be associated with a wide range of syndromes, particularly different hamartomatoses including ENS [15 16, 17, 18]. This condition typically presents as a solitary, hairless, well-marginated skin lesion. Other presentations, like bullous lesions, are less frequent [18].

In summary, we report a new case of ENS with various organ abnormalities that emphasize the multisystemic nature of this condition. Central nervous system lipomas and aplasia cutis are clinical features sometimes associated with different types of hamartomatoses and developmental abnormalities. Skeletal findings in our patient were not linked to hypophosphatemic rickets like in other cases, but the ipsilateral localization of bone and skin disease suggests the role of postzygotic mosaicism as the main etiopathogenic factor in the development of the lesions. Further studies should identify the precise altered gene expression responsible of this striking clinical presentation.


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