Wednesday 11 July 2018

Gorlin syndrome, nevoid basal cell carcinoma syndrome, or Gorlin-Goltz syndrome

It «is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. (...). Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. (...). Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. (...). Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors (...). Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries (...). Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull [1].» «Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years [2].»
Mutations in the PTCH1 (protein patched homolog 1) gene cause Gorlin syndrome [1,3]. This protein «is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. This gene functions as a tumor suppressor. The PTCH1 gene product is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgehog binds PTCH1, smoothened is released and signals cell proliferation [3].» «The characteristic features of Gorlin syndrome can also be associated with a chromosomal change called a 9q22.3 microdeletion, in which a small piece of chromosome 9 is deleted in each cell. This deletion includes the segment of chromosome 9 that contains the PTCH1 gene [1].
«Gorlin syndrome is inherited in an autosomal dominant pattern [1].»
«Life expectancy (...) is not significantly different from average [2].»
These patients have a relative contraindication for radiotherapy [4].
Bibliographic reference:
[1] Gorlin syndrome. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/gorlin-syndrome#genes. Published 2018. Accessed July 11, 2018.
[2] Evans DG, Farndon PA. Gorlin syndrome - Conditions - GTR - NCBI. Ncbi.nlm.nih.gov. https://www.ncbi.nlm.nih.gov/gtr/conditions/C0004779/. Accessed July 11, 2018.
[3] PTCH1. En.wikipedia.org. https://en.wikipedia.org/wiki/PTCH1. Published 2017. Accessed July 11, 2018.
[4] Singer L, Yom SS. Chapter 1 - Skin Cancer. In: Hansen EK, Roach III M. Handbook Of Evidence-Based Radiation Oncology. 3rd ed. Cham, Switzerland: Springer; 2018:10. Available at: https://doi.org/10.1007/978-3-319-62642-0.

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