pathogenesis

Last reviewed 01/2018

The Gorlin-Goltz syndrome gene has been mapped to chromosome 9q22.3-q31 - there is accumulating evidence suggests that a gene at this locus normally functions as a tumour suppressor. Other genes nearby may also need to be modified or deleted to allow full development of the syndrome - a multiple 'hit' hypothesis. The trigger for mutation may be sunlight and with a fairly rapid lag time, usually months, compared to the development of BCC's in non-Gorlin's individuals. Inheritance of the gene defect seems to be autosomal dominant with variable penetrance.

As a result of a tumour suppressor abnormality, patients with Gorlin-Goltz syndrome are predisposed to develop several neoplasms including cutaneous melanoma, medulloblastoma, meningioma, breast carcinoma, non-Hodgkin's lymphoma and ovarian fibroma (1,2). However, iin contrast to other autosomal dominant cancer predisposition syndromes, developmental malformations, hamartomas, and dysplastic lesions are consistent and striking components of Gorlin-Goltz syndrome (1,2)

Ref:

(1) R.J. Gorlin, Nevoid basal cell-carcinoma syndrome [review]. Medicine (Baltimore) 66 (1987), pp. 98-113

(2) R.J. Gorlin, Nevoid basal cell carcinoma syndrome [review]. Dermatol Clin 13 (1995), pp. 113-125.