Gorlin-Goltz syndrome

Gorlin-Goltz syndrome, also known as the basal cell nevus syndrome, nevoid basal cell carcinoma syndrome, or just Gorlin syndrome, is a rare phakomatosis characterized by multiple odontogenic keratocysts (OKC), multiple basal cell carcinomas (BCC) and other abnormalities.

Epidemiology

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

Clinical presentation

• 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)

Pathology

Genetics

It is an autosomal dominant syndrome with complete penetrance and variable expressivity. It is related to a mutation in the PTCH tumor suppressor gene on chromosome 9, which encodes for the "Sonic Hedgehog" receptor ³. 35-50% of affected individuals are the result of new mutations. Individuals with the syndrome are sensitive to ionizing radiation, with one study showing accumulation of p53 in exposed cells ³. Patients with Gorlin syndrome may be hypersensitive to and contraindicated from receiving radiation therapy.

Diagnosis

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 carcinoma: >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 osseous radiolucencies

• ovarian fibroma

• medulloblastoma

History and etymology

It was described by Robert James Gorlin (1923-2006) and Robert William Goltz (1923-2014) ⁵ in 1960 ², although cases had been reported in the literature prior to this.