Identification of Somatic KRAS Mutation in a Korean Baby with Nevus Sebaceus Syndrome

Nevus sebaceus is a benign hamartoma of the epidermis, hair follicles, and sebaceous and apocrine glands. It typically appears as a yellow-orange to pink, finely papillomatous alopecic plaque that is often oval or linear. It usually presents at birth, preferentially affects the scalp and face, and is not uncommon, occurring in approximately 1 in 1,000 live births [1]. A recent study by Groesser et al. [1] reported that 95% of patients with nevus sebaceus lesions had somatic mutations in the HRAS gene and 5% had mutations in the KRAS gene, and the HRAS c.37G>C mutation was present in 91% of all lesions as the predominant mutation; approximately 3% of lesions had KRAS c.35G>A (p.Gly12Asp) as the next common mutation. These mutations were not detected in either non-lesional skin tissue or in whole blood, confirming nevus sebaceus as a ‘mosaic RASopathy’. We report the case of a female infant with nevus sebaceus, in whom a somatic KRAS mutation was identified by Sanger sequencing in a cutaneous lesion. A 3-day-old female infant was transferred to our institution owing to skin lesions on the scalp, especially over the left parietal and occipital areas. The patient had a slippery, skin-colored, hairless, orange-peel-like linear plaque on her left parietal scalp and face (Fig. 1A) and a round plaque on her occipital scalp (Fig. 1B). Facial examination revealed a limbal dermoid with a skin-colored pedunculated papule on the left eyelid (Fig. 1C). Magnetic resonance imaging of the head showed an arachnoid cyst in the anterior portion of the left temporal lobe, and computed tomographic scanning of the orbit showed a calcified nodular lesion in the medial portion of the left orbit. Echocardiography showed that the patient had an atrial septal defect. A biopsy specimen taken from the plaque showed hyperkeratosis, acanthosis, numerous sebaceous glands, and malformed hair follicles (Fig. 2), consistent with nevus sebaceus. After obtaining informed consent from the patient’s parents, tissue samples (~5 mm) were collected from a nevus sebaceus lesion of scalp and from normal skin by elective punch biopsy and were subjected to fibroblast culture for expansion. Genomic DNA was extracted from cultured skin fibroblasts as well as from peripheral blood leukocytes using the Wizard Genomic