Unusual Neurological Presentation of Nevoid Basal Cell Carcinoma Syndrome (Gorlin-Goltz Syndrome)

Dear Editor, Nevoid basal cell carcinoma syndrome (NBCCS; also called Gorlin-Goltz syndrome, MIM: 109400) is a rare autosomal dominantly inherited disorder caused by defects in the hedgehog signaling resulting in constitutive pathway activity and tumor cell proliferation.1 In addition to basal cell carcinoma from a young age, distinguishing features are keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, skeletal and other developmental abnormalities, and neurological involvement (e.g., meningeal calcifications, intracranial tumors, seizures, congenital hydrocephalus, intellectual disability, and movement disorders).1,2 Here we report two patients with unusual neurological presentations of NBCCS. Written informed consent was obtained from both patients, and their family histories were negative. A 24-year-old female was referred because of bilateral frontal-temporal headache of mildto-moderate intensity without signs of increased intracranial pressure and which responded to non-steroidal anti-inflammatory drugs with short-lasting relief. She had a prenatal diagnosis of macrocephaly with mild ventriculomegaly and a mild delay in motor development, but no intellectual disability. She had undergone surgery for keratocystic odontogenic tumors in her infancy. A physical examination revealed a prominent forehead, mild hypertelorism, macrocephaly (head circumference 60 cm, ≥97th percentile), mandibular prognathism, and pits on the palms (Fig. 1A). The findings of a neurological examination were normal. Extensive laboratory testing, including of pituitary and parathyroid hormones, produced negative results. Electroencephalography (EEG) results were also normal, and skeleton X-rays and cardiac and pelvic ultrasonography produced unremarkable findings. A maxillofacial computed tomography (CT) scan revealed a cystic lesion in the body of the left mandible (Fig. 1B). Head CT showed diffuse calcifications of the falx cerebri and tentorium cerebelli (Fig. 1C), and a microadenoma of the pituitary gland and a choroid plexus papilloma of the left lateral ventricle were evident in magnetic resonance imaging (MRI). Dermoscopy showed multiple melanocytic nevi (Fig. 1D) and a basal cell carcinoma of the trunk (Fig. 1E). PTCH1 mutations were ruled out. The second patient, a 16-year-old female, was admitted because of developmental delay and behavioral disturbances. She had previously received surgery for two nodular basal cells carcinomas below the eyelids (Fig. 1F). Her full IQ was 55 on the Wechsler Intelligence Scale for Children (revised edition). A physical examination revealed short stature (height 158 cm, ≤3rd percentile), prominent eyebrows, scapular winging, and marked scoliosis of the dorsallumbar spine with hyperkyphosis of the dorsal tract. A neurological examination disclosed moderate-to-severe intellectual disability, stereotypical motor behavior (e.g., swinging and clapping the hands), and sphincter incontinence. Several hyperpigmented basal cell carcinomas were observed over her face, especially around the eyes (Fig. 1G). Dermoscopy also revealed multiple pits on the palms and a melanocytic nevus of the right shoulder. The findings Manuela Pennisi Giuseppe Lanza Mariagiovanna Cantone Carmelo Schepis Raffaele Ferri Rita Barone Rita Bella