Basal Cell Nevus Syndrome at a Glance
- A rare autosomal dominant disorder with phenotypic abnormalities that include developmental anomalies and postnatal tumors, especially basal cell carcinomas (BCCs).
- The three most characteristic abnormalities are tumors such as medulloblastomas or BCCs, pits of the palms and soles, and odontogenic cysts of the jaw.
- Related findings include calcification of the falx cerebri, enlarged body habitus, and skeletal abnormalities of the ribs and skull.
- Diagnosis is suspected in a patient with multiple BCCs arising at an unexpectedly early age with an average age of onset of 21 years.
- Histologic features of tumors in BCNS patients are similar to those of sporadic BCCs or medulloblastomas.
- Several new therapeutic agents, including SMO antagonists and celecoxib, have been shown to have efficacy in treating disease along with photodynamic therapy, imiquimod, and 5-fluorouracil.
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
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.
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.
Figure 116-1Graphic Jump Location
The mammalian hedgehog signaling pathway. PTCH1 is the receptor for the growth factor hedgehog and inhibits the function of smoothened (SMO) by sequestering it in an inactive state ...