Gorlin-Goltz syndrome

The Gorlin-Goltz syndrome also known as the basal cell naevus syndrome, is a phakomatosis. 

Epidemiology

The condition is thought to occur in ~ 1 in 60,000 live births while 0.4% of patients with a basal cell carcinoma are estimated to have Gorlin syndrome. ~ 2% and 22% of patients with a basal cell carcinoma younger than 45 years and 19 years of age respectively are estimated to have the syndrome. 

Genetics

It is an autosomal dominant syndrome with complete penetrance and variable expressivity. 35 - 50% of affected individuals are due to new mutations. It is related to mutation in PTCH tumour suppressor gene on chromosome 9. Individuals with the syndrome are sensitive to ionising radiation.

Diagnostic criteria

A clinical diagnosis can be made using major and minor criteria. To make the diagnosis, either two major or, one major and two minor criteria must be met.

Major criteria

• basal cell cancers : > 2 or 1 under the age 20
• odontogenic keratocysts (see case 1)
• palmar pits : 3 or more
• bilamellar calcification of the falx cerebri
• rib anomalies : bifid rib (see image), fused, splayed
• first degree relative with Gorlin syndrome

Minor criteria

• macrocephaly
• frontal bossing, cleft lip or hypertelorism
• Sprengel deformity,  pectus excavatum or pectus carinatum, syndactyly
• bridging of the sella turcica, hemivertebrae, flame shaped radiolucencies
• ovarian fibroma
• medulloblastoma

Clinical features

• multiple basal cell carcinomas, often at puberty and in adolescence
• craniofacial anomalies
  
  • odontogenic keratocysts, often multiple
  • frontal bossing
  • hypertelorism : 5%
  • macrocephaly
  • calcified falx cerebri
  • calcified tentorium and petroclinoid ligaments
  • cleft lip
  • ocular defects including 
    • coloboma of the iris
    • microphthalmia
  • bridging of the sella turcica
  • high arched palate
  • agenesis of the corpus callosum (occurs in ~10% of cases)
• musculoskeletal anomalies
  • shortened 4^th metacarpal bones
  • bifid rib or other rib abnormality (fusion, partial agenesis, etc.)
  • palmar and plantar pitting : defects of basal cell maturation
• neoplasms / hamartomas
  • medulloblastoma : especially in males (M : F ~ 3 : 1)
  • calcified ovarian fibroma
  • lymphomesenteric cysts
  • fetal rhabdomyoma
  • cardiac fibroma(s)

Etymology

It was first described by R.J Gorlin and R.W. Goltz in 1960 ²