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Basal cell nevus syndrome (BCNS), also known as nevoid basal cell carcinoma syndrome and Gorlin syndrome [Online Mendelian Inheritance in Man (OMIM) #109400], is a rare autosomal dominant disorder associated with a panoply of phenotypic abnormalities that can be divided into developmental anomalies and postnatal tumors, especially basal cell carcinomas (BCCs).1 Although individual aspects had been reported previously, their syndromic association was first appreciated widely in the late 1950s.2,3
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The prevalence of BCNS is variously estimated to be 1 in 60,000 and 1 in 120,000 persons.4,5 The syndrome affects both sexes and occurs in a wide variety of cultural groups, and therefore does not have a predilection for a particular skin type. The condition appears to have complete penetrance but variable expressivity of traits, such that their clinical presentation within families is nonuniform. Further, as with many dominantly inherited conditions, new mutations are common. As a result, many patients may have no apparent affected ancestors or siblings.
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Almost all known BCNS patients thus far carry mutations in the PATCHED1 (PTCH1, UniGene Hs. 494538) gene residing on the long arm of chromosome 9.6,7 PTCH1 plays a central role in the hedgehog signaling pathway that is essential for the establishment of normal body and limb patterning in metazoan organisms.8 The PTCH1 locus behaves like a classic tumor suppressor gene (Fig. 116-1). The appearance of BCCs in small numbers at an older age in sporadic cases and in larger numbers at a younger age in patients with BCNS is reminiscent of differences in sporadic and hereditary cases of retinoblastoma.9 BCNS, like other tumor susceptibility syndromes, is inherited in an autosomal dominant manner, with inheritance of a loss-of-function allele followed by somatic loss of the remaining copy before tumor formation.
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