Gorlin’s Sundrome (Nevoid Basal Cell Carcinoma Syndrome)
Incidence
 1 in 57,000 to 1 in 150,000
 M=F
Aetiology
 Autosomal dominance, 40% new mutations
 caused by germline mutations of the PTCH gene (chromosome 9q) – likely to be
a tumor suppressor gene
 PCTH codes for a transmembrane protein, which represses transcription (in
certain cells) of genes encoding members of the transforming growth factor
(TGF)–beta and Wnt families of signaling proteins.
 DNA from sporadic basal cell carcinomas also has allelic loss in the nevoid basal
cell carcinoma syndrome (NBCCS) region with inactivating mutations of the
remaining allele, suggesting that the gene may play a role in a final common
pathway to oncogenesis in basal cell carcinomas.
 Gailani et al (1992) showed that inactivation of patched gene is probably a
necessary step in basal cell carcinoma development, even in patients without
Gorlin syndrome.
 Follows Knudson hypothesis - a theory of oncogenesis stating that normal cells
require 2 mutagenic hits (2 distinct episodes of DNA damage) to produce a
cancer. Patients with retinoblastoma, Gorlin syndrome, and similar syndromes
have a constitutional (germline) defect in the DNA sequence in 1 of the 2 gene
copies of a tumor suppressor gene. The presence of a defect in 1 of the 2 gene
copies is not sufficient to cause a cancer. If a second DNA injury or loss of the
normal remaining allele occurs at the same locus (the second hit), the cell may
become malignant.
Features
 Usually presents with BCC in 2nd to 3rd decade or keratocysts of mandible in 2nd
decade
Diagnostic criteria
 Requires 2 major criteria or 1 major and 2 minor criteria
major criteria
(1) more than 2 BCCs or 1 BCC in patients younger than 20 years
a. 50% of whites had their first BCC by age 21.5 years, and 90% of them had
it by age 35 years
(2) odontogenic keratocysts of the jaw (proven by histologic analysis); (80%)
a. Untreated, they can lead to major tooth disruption and fracture of the jaw.
(3) 3 or more palmar or plantar pits - more pronounced when the hands and feet are
soaked in warm water for up to ten minutes.
(4) lamellar calcification of the falx cerebri <20years old
(5) bifid, fused, or markedly splayed ribs – usually rib 3,4,5
(6) first-degree relative with NBCCS.
minor criteria:
(1) macrocephaly (>97th percentile)
(2) congenital malformations, such as cleft lip or palate(3-5%), frontal bossing,
coarse facies, and moderate or severe hypertelorism;
(3) other skeletal abnormalities
a. Sprengel deformity
b. marked pectus deformity
c. syndactyly of the second and third fingers
d. brachymetacarpia usually 4th
(4) radiologic abnormalities, such as bridging of the sella turcica, vertebral anomalies,
modeling defects of the hands and feet, or flame-shaped lucencies of the hands
and the feet
(5) ovarian fibroma(20%) or medulloblastoma (5%)
Investigations:


Xrays - Skull xrays, CXR, spinal xray, OPG
Genetic tests not widely available (not in WA)
Morbidity/mortality
 Life expectancy in NBCCS is not significantly different from average.
 The major problem is with the cosmetic effect of treatment of multiple skin
tumors and usually, to a lesser extent, treatment of jaw keratocysts.
 A poor cosmetic outcome can lead to social difficulties, including difficulty
holding employment.
Management
 Geneticists, pediatrician
 As required - neurologist and/or a neurosurgeon, a cardiologist and/or a cardiac
surgeon, a gynecologist, a dentist and/or an oral surgeon, a plastic surgeon, and an
ophthalmologist.
 Basal Cell Carcinomas
o Sun protection
o Surveillance
o Chemoprevention with retinoids - isotretinoin
o Treatment – surgery, laser ablation, photodynamic therapy, and topical
chemo/immuno therapy
o Avoid radiotherapy!
 Keratocysts
o Enucleations with peripheral ostectomy and/or cryosurgery
o lifetime follow-up radiography is imperative