Gorlin Goltz Syndrome
Gorlin and Goltz’s eponymous syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant disorder distinguished by multisystemic developmental abnormalities secondary to mutations in the patched-1 (PTCH1) gene.
Causes of Gorlin Goltz Syndrome
Goltz syndrome has also been linked to mutations in PTCH2 and SUFU.
The disease is most commonly inherited with complete penetrance and variable expressivity via a suspected two-hit model in which an inherited mutation in one PTCH1 allele is followed by an acquired loss-of- function mutation in the second allele.
Twenty to 40% of patients are estimated to acquire Gorlin-Goltz syndrome by de novo mutations of PTCH1 however.
Symptoms of Gorlin Goltz Syndrome
BCCs are typically non-invasive, and develop between puberty and age 35, with an average age of onset of 25.
BCCs of varying number, size, and appearance occur most commonly in sun-exposed areas, and have a higher incidence in western countries, possibly secondary to greater exposure to ultraviolet (UV) radiation.
Palmar and plantar pits are permanent, benign, red to dark brown or black papules that appear by age 10 in 30-65% of patients, and are present in more than 85% of patients older than 20 years of age.
Odontogenic keratocysts are jaw cysts with a characteristic radiographic appearance that are frequently recurrent, and affect 85-90% of patients, appearing as early as 10 years of age.
Calcification of the falx cerebri, evident on X-ray, increases with age, and affects 65% of patients in the United States, but rarely causes symptoms.
Strabismus, of which esotropia and esophoria may be more prevalent than exotropia and exophoria, occurs in 10-20% of patients.
Myelination of the retinal nerve fibers may occur bilaterally and involve the retina more extensively in Gorlin-Goltz syndrome patients than they do in the general population.
This may cause visual field defects or decreased visual acuity.
Eyelid cysts occur in approximately 5-10% of patients.
Microphthalmia affects 1-2% of patients.
Diagnosis of Gorlin Goltz Syndrome
Diagnosis of Gorlin-Goltz syndrome may be established when 2 major, or 1 major and 2 minor criteria are present.
The major criteria
Multiple BCCs or one occurring under the age of 20 years.
Histologically proven odontogenic keratocysts of the jaw.
Palmar or plantar pits (3 or more).
Bilamellar calcification of the falx cerebri.
Bifid, fused, or markedly splayed ribs.
First-degree relative with NBCCS.
The minor criteria
Macrocephaly (adjusted for height).
Congenital malformation: cleft lip or palate, frontal bossing, coarse face, or moderate or severe hypertelorism.
Other skeletal abnormalities: Sprengel deformity, marked pectus deformity, or marked syndactyly of the digits.
Radiological 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 fibroma.
Medulloblastoma.
Treatment of Gorlin Goltz Syndrome
Surgery
Mohs microsurgical excision is the mainstay of treatment for BCCs. This technique allows for complete removal of lesions whilst preserving the amount of non-involved tissue.
Medical therapy
Medical therapy for Gorlin-Goltz syndrome and BCCs is a trending topic of research, and a variety of therapies have become available in recent years.
Superficial BCCs without hair follicle involvement are treated by topical use of tretinoin cream and fluorouracil applied to the affected areas twice daily.
Novel therapies like vismodegib (Erivedge), a first-in-class hedgehog gene inhibitor with recent FDA approval for advanced and invasive BCC is also a therapeutic option.