PENS syndrome: a new neurocutaneous phenotype

Abstract

Background: The central nervous system originates ontogenetically from the ectoderm and therefore numerous neurocutaneous syndromes exist.

Objective: We describe a novel neurocutaneous syndrome with characteristic epidermal papules and plaques associated with mild psychomotor retardation and epilepsy with a good prognosis.

Methods: We investigated history, clinical features, laboratory parameters including karyotype, histopathological and immunohistological examination, electron microscopy, HPV infection, EEG and neurologic imaging in patients with an unusual symptom complex.

Results: Six children are reported with characteristic keratotic papules and plaques of 'gem-like' appearance, randomly distributed on the trunk and the proximal part of the limbs. Four patients were unrelated and two were siblings. The cutaneous lesions appeared congenitally or developed soon after birth. The skin lesions were rounded or of an irregularly polycyclic shape, ranging from 0.5 to 1.5 cm in diameter. A few to eighteen lesions were present. The lesional surface was rough and of white or yellowish color. Histopathological examination showed acanthokeratosis, but immunostaining for keratins and melanocytes, electron microscopy and laboratory results were within normal range. During the natural course of the disease the lesions were stable and asymptomatic. All but one of our six patients developed neurologic signs and symptoms during the first year of life, in the form of epilepsy and psychomotor delay. Five children had low intellectual performance together with EEG abnormalities and some had MRI changes of the brain. One patient had marked language impairment. The central nervous system involvement had a peculiar benign and self-limiting course and total normalization occurred in one case.

Limitations: We present only a small series of patients.

Conclusion: Cutaneous lesions showing identical clinical and microscopical features, but without any extracutaneous abnormalities, have recently been described by Torrelo et al. [J Am Acad Dermatol 2011;64:888-892] under the designation 'papular epidermal nevus with "skyline" basal cell layer (PENS)'. An association of such nevi with neurologic abnormalities had so far only been published in the 'Atlas of Genodermatoses' edited by Caputo and Tadini. We believe that this unique and otherwise undescribed symptom complex is a new neurocutaneous phenotype that may be called PENS syndrome. Whether this new syndrome can be categorized as a distinct phenotype within the group of epidermal nevus syndromes remains speculative and has to be clarified by further investigations.