Spitz_Genodermatoses, 3e

Basal Cell Nevus Syndrome

Synonym(s)

Nevoid basal cell carcinoma (BCC) syndrome Gorlin syndrome, Gorlin-Goltz syndrome

Inheritance

Autosomal dominant (AD) PTCH1 gene on 9q22.32 (50%-85%) PTCH2 gene on 1p34.1 SUFU gene on 10q24.32 (5%)

Prenatal Diagnosis

DNA analysis if mutation known in family

Incidence

~1:60,000; M = F

Age at Presentation

Birth (macrocephaly, skeletal anomalies) or childhood (jaw cysts, BCC)

Pathogenesis

Tumor suppressor gene, PTCH1 , encodes “Patched 1,” a transmembrane receptor in the hedgehog (Hh) signaling pathway that controls cell fate, patterning, and growth during development; PTCH1 decreases cell proliferation by inhibiting Smoothened (Smo); disrup tions in PTCH1 allow accelerated tumor growth characteristic of basal cell nevus syndrome (BCNS) SUFU encodes “suppressor of fused,” which downregulates Hh/Smo signaling by Gli transcription factors; mutations cause constitutive Gli activation, followed by sustained transcription and cell growth Skin BCCs—multiple, quiescent, whitish to skin-colored to dark-colored, dome-shaped “nevi”/papules on the face, neck, trunk; some transform to active BCC (growth, erythema, crusting, bleeding) Palmoplantar pits—“punched-out” or “pin-prick” 2-mm pits, occasionally infected; rarely develop into BCCs; Milium, epidermoid cysts Musculoskeletal Macrocephaly; jaw cysts (odontogenic keratocysts)—painless cysts that disrupt tooth roots, cause tooth loss, potential jaw fracture, usually before age 30; rare—lining with malignant potential (ameloblastoma) Frontal bossing or broad nasal root, bifid ribs, wedge-shaped vertebrae, downsloping shoulders, kyphoscoliosis; cleft lip/palate; polydactyly Central nervous system Calcification of falx cerebri (90% by age 20 years), agenesis of corpus callosum Cognitive deficit, meningiomas; medulloblastoma ( SUFU , 33% risk) Eyes Hypertelorism, unilateral or bilateral congenital blindness, cataracts, colobomas, strabismus Genitourinary Ovarian fibromas, fibrosarcoma, undescended testes Cardiac Fibromas in the first year

Key Features

Differential Diagnosis

Bazex syndrome Unilateral linear nevoid BCCs

Melanocytic nevi Rombo syndrome Xeroderma pigmentosum (XP) (p. 278)

Copyright © 2024 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. Laboratory Data

Skin biopsy; head circumference Skeletal x-ray of the skull, maxilla, mandible, ribs, vertebrae (only if clinical criteria fail—­ radiation risk) Molecular genetic testing

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