Nevoid basal cell carcinoma syndrome

Nevoid basal cell carcinoma syndrome
Updated: 05/19/2020
© Jun Wang, MD, PhD

General features
  • AKA Gorlin syndrome, basal cell nevus syndrome, etc
  • Autosomal dominant 
  • Germline mutation of PTCH1
  • Multiple developmental abnormalities
  • Increased risk for childhood medulloblastoma
Pathogenesis
  • Inactivation of PTCH1, receptor for hedgehog protein
  • Loss of suppression of Smoothened (SMO)
  • Probably downstream over activation of transcription factors Gli1 and/or Gli2
Clinical presentations
  • Major manifestations
  •  Minor manifestations
    • Childhood medulloblastomas
    • Craniofacial anomalies: Cleft lip/palate, macrocephaly, frontal bossing, hypertelorism
    • Vertebral/rib anomalies, such as bifid/splayed/extra ribs or bifid vertebrae
    • Polydactyly
    • Cardiac or ovarian fibromas, often bilateral
    • Lymphomesenteric or pleural cysts
    • Ocular anomalies (coloboma, cataract, glaucoma)
Genetic abnormalities
  • PTCH1: Most common, mutations seen in nevoid basal cell carcinoma syndrome, sporadic basal cell carcinoma, medulloblastoma
  • SUFU: Regulate SHH/patched pathway, mutations associated with nevoid basal cell carcinoma syndrome and childhood medulloblastoma
Diagnosis
  • Clinical diagnosis with two major criteria or one major criteria and two minor criteria
  • Major criteria
    • More than two basal cell carcinomas (BCCs) or one under the age of 20 years
    • Odontogenic keratocyst of the jaw proven by histology
    • Three or more palmar or plantar pits
    • Lamellar (sheet-like) calcification of the falx cerebri or clear evidence of calcification in an individual younger than age of 20 years
    • Bifid, fused, or markedly splayed ribs
    • First-degree relative with NBCCS
  • Minor criteria
    • Childhood medulloblastoma
    • Congenital craniofacial anomalies: cleft lip or palate, frontal bossing, coarse face, moderate or severe hypertelorism
    • Other skeletal abnormalities: Sprengel deformity, marked pectus deformity, marked syndactyly of the digits
    • Radiologic abnormalities: Bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet, or flame-shaped lucencies of the hands or feet
    • Ovarian fibromas
  • Molecular testing if clinical diagnosis in question
    • PTCH1
    • SUFU
    • PTCH2
Management
  • Cancer surveillance
  • Genetic counseling
  • Prevention and treatment of basal cell carcinoma
  • Treatment of other presentations accordingly, including odontogenic keratocysts, medulloblastoma, etc
  • Treatment of vitamin D deficiency for patients who adopt strict sun protection


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