Introduction

Epidermal nevus syndrome (ENS) (Schimmelpenning-Feuerstein-Mims syndrome) is a sporadic neurocutaneous disorder in which epidermal nevi are found in association with deformities and dysplasias of the skin, eyes, skeleton, heart and brain. Occasionally, tumour development has also been reported [1, 2]. Happle [3] has developed a classification of ENS based on the type and distribution of the epidermal nevi and associated symptoms. The genetic basis presumably consists of mosaicism of an autosomal lethal mutation. The condition is rarely encountered in children, as only about 450 cases have been reported; the sex ratio is 1:1. A wide spectrum of cerebral MRI findings has been described, including hemimegalencephaly, heterotopia, hemiatrophy, cortical atrophy, ventricular dilatation, vascular anomalies, porencephaly and tumours; calcifications of the periventricular white matter have been visualised on CT [4, 5, 6, 7, 8]. Skull asymmetry can occur [7, 9]. Skeletal lesions, such as bone cysts or fibrous dysplasia have rarely been observed [4, 6, 8, 10, 11].

Case report

The patient, an 11-year-old boy, is the only child of non-consanguineous healthy parents. The family history did not identify any first- or second-degree relatives with findings of ENS. The propositus and his mother had macrocephaly, with the head circumference being 1 cm above the 97th centile, and the father's head circumference was between the 90th and 97th centiles.

Our patient had hemihypertrophy of his right leg involving bone and soft tissue, and this had first been noted in the first year of life. The child was admitted to our hospital because of sudden-onset generalised swelling of his leg. He had an extensive epidermal nevus on the right side of his trunk (Fig. 1), as well as epidermal nevi extending over large parts of the midline of the upper back, following Blaschko lines (a system of lines caused by pigment mosaicism on the surface of the human body resulting from the existence of two different cell lines; linear nevi and dermatoses follow Blaschko lines [12]). A further epidermal nevus was located to the inner midline of the right arm. Additionally, patchy skin pigmentations were present on his trunk. There were several subtle alopecic patches and one small area of hypopigmented hair on the scalp. The first pigmentary skin lesions were noted at about 6 months of age, and they were reported to be unchanged since the age of 2 years.

Fig. 1.
figure 1

Papillomatous epidermal nevus on the right side of the trunk (the midline forms a visible boundary)

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Our patient had left-sided amblyopia because of corneal clouding and a left-sided conjunctival and corneal lipodermoid tumour, which had been surgically removed at the age of 3 years. A recent MRI examination of the eyes demonstrated a small left coloboma involving choroid and retina.

Cardiac examination revealed aortic isthmus stenosis without haemodynamic relevance. Neurological investigation, including EEG, showed no abnormalities. Mental development was appropriate for his age.

Cerebral MRI revealed asymmetry with cortical hypoplasia on the left side and giant cystic enlargement of Virchow-Robin spaces (Fig. 2). There were no calcifications on CT.

Fig. 2a, b.
figure 2

MRI of the brain. a Axial T2-weighted and b coronal MIR sequence shows asymmetry with slight enlargement of the left lateral ventricle and deep sulci on the left side consistent with cortical hypoplasia. Giant tumefactive Virchow-Robin spaces on the left side

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Radiographs of the legs showed extensive lytic lesions of the proximal tibiae (Fig. 3). These symmetrical lesions were interpreted as an unusual manifestation of polyostotic fibrous dysplasia.

Fig. 3a–d.
figure 3

Lower limbs. a, b AP radiographs show extensive predominately lytic lesions of the proximal tibiae. The lesions are symmetrical, an unusual manifestation of polyostotic fibrous dysplasia. c Coronal T1-weighted MRI shows asymmetry of the legs with swelling of the right leg. The intramedullary lesions in the proximal diaphysis of the tibiae are of homogeneously decreased signal. d Coronal STIR sequence shows inhomogeneous signal from the right-sided lesion and markedly increased signal intensity with several small septations from the left-sided lesion

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In addition, we suspected our patient of having lymphoedema of the right leg because there were no signs of infection, phlebitis, angiomatous malformations or neoplasia, and diurnal fluctuation with improvement at night was noticed. MRI showed asymmetry of the legs with hypertrophy of the right leg. There were intramedullary lesions in the proximal diaphysis of the tibiae with several septations. On T1-weighted images, the lesions showed decreased signal intensity, whereas on T2-weighted images they revealed inhomogeneous signal intensity on the right and marked increased signal intensity on the left side. The soft tissue of the right leg was markedly thickened and the high signal intensity on the T2-weighted images corresponded to lymphoedema of the right leg (Fig. 3c, d).

Discussion

Our patient showed the characteristic pigmented lesions of ENS. In contrast to the majority of patients with ENS, in whom the pigmentary lesions are also located on the face, our patient showed only trunk and extremity cutaneous lesions. Fifty percent of the cases in the literature have severe-to-moderate neurological involvement. The most common symptom (40%) is mental retardation [9]. Other abnormalities that have been described include focal and generalised epilepsy, hyperkinesia, hemiparesis, quadriplegia, cranial nuclei abnormalities (mostly of the 6th, 7th and 8th nerves), cortical blindness and astrocytoma. One patient had a symptomatic cerebral arteriovenous malformation [10]. The cerebral asymmetry and left-sided cortical hypoplasia in our patient are in accordance with reported cerebral findings. Even though porencephalic cysts [8, 13] and arachnoid cysts [14] are described, dilatation of the Virchow-Robin spaces, as in our case, has not been reported. Despite the evident cerebral manifestations demonstrated on MRI, our patient has no neurological signs.

Hemihypertrophy of the leg, involving bone and soft tissue without underlying haemangioma, was seen in a patient of Solomon and Esterley [15] and in another patient with hypertrophy of the right leg and left arm. Extensive varicosities of both legs, gigantism of the hands and arms and hemihypertrophy of the right half of the tongue was seen in a 25-year-old patient described by Fretzin and Lawrence [9].

Cystic skeletal changes occur in the skull, mandible and long bones such as the humerus and femur [15]. Schimmelpenning [4] described a 43-year-old woman with ENS in whom monostotic fibrous dysplasia in the skull had progressed from childhood to adulthood. In one of the patients of Solomon and Esterley [15], repeated fractures required amputation [15]. The osseous lesions seen in ENS are indistinguishable from fibrous dysplasia. In the McCune-Albright syndrome, fibrous dysplasia manifests in association with patchy skin pigmentation and sexual precocity. It has also been observed in association with hyperthyroidism, hyperparathyroidism and a number of other conditions, including gigantism, diabetes mellitus, hypophosphataemic rickets and arteriovenous fistula. Except for hypothyroidism, the association is thought to be coincidental [16].

In summary, the complex manifestations of ENS seen in our patient are rare. Our case illustrates the association of characteristic dermatological findings on the trunk, extremities and scalp with the pathological findings in the brain, eye and bones, and lymphoedema, which we describe here for the first time. Patients with comparable skin lesions should undergo cerebral MRI, even if they have no sebaceous nevi on the scalp or no neurological disturbances. The patients should be regularly observed in respect to their pigmentary changes, since basal cell carcinoma can arise in 10–15%. Furthermore, tumour surveillance, including abdominal US examination, is recommended. For fibrous dysplasia, limited surgery may be required for prevention and management of complications.