A number sign (#) is used with this entry because of evidence that nevus comedonicus (NC) is caused by somatic mutation in the NEK9 gene (609798) on chromosome 14q24.Description
Nevus comedonicus (NC) is a rare type of epidermal nevus with predilection for the face and neck area. The condition develops within the first decade of life in most patients. NC is characterized by dilated, plugged follicular ostia containing lamellar keratinaceous material and grouped in a honeycomb pattern; the distribution of lesions may be unilateral, bilateral, linear, interrupted, segmental, or along the lines of Blaschko. NC may be nonpyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Histologically, the lesions are large, grouped, dilated follicular ostia devoid of hair shafts but filled with keratin layers (summary by Tchernev et al., 2013).Clinical Features
Levinsohn et al. (2016) studied 3 unrelated patients with nevus comedonicus. The first was a 43-year-old woman with a 6 cm by 3 cm linear lesion on the back consisting of grouped comedones, with a history of inflammatory cysts within the lesion. The second was a 10-year-old boy who presented at birth with a shiny flat lesion on the right lower buttock, which developed inflammatory cysts with cribriform scarring and comedones at 10 months of age. By 10 years of age, his lesion extended inferiorly to the posteromedial right thigh, and consisted of a 10 cm by 2 cm plaque composed of several atrophic cribiform scars and scattered pink comedones, with another smaller plaque below it. The third patient was a 19-year-old woman who had a 4 cm by 1 cm lesion on the scalp that appeared at birth, which subsequently developed alopecia, comedones, and rare inflammatory cysts. Histopathologic examination of NC lesions revealed follicles with dilated ostia adjacent to normal follicles. The abnormal follicles showed marked acanthosis and papillomatosis of the outer root sheath. In addition, large cystic structures filled with keratin were present in the deep dermis. Accumulated keratin was present without evident hair shafts. The authors noted that although lesional tissue was limited, NC comedonal follicles did not appear to have associated sebaceous lobules. Interfollicular skin was normal clinically and histologically.Population Genetics
Tchernev et al. (2013) stated that nevus comedonicus has a prevalence of 1/45,000 to 1/100,000, with no gender or racial preference.Molecular Genetics
By whole-exome sequencing on DNA from blood and tissue samples from 3 unrelated patients with nevus comedonicus, Levinsohn et al. (2016) identified heterozygous somatic mutations in NC lesions from all 3 patients (see 609798.0003-609798.0005). Functional analysis suggested that the NC mutations result in a gain of function, and immunolocalization studies of NC lesional tissue showed abnormal localization of multiple markers of hair follicle and epidermal differentiation.