FaCD Online Syndrome Fact Sheet
Last updated: 29 Jul 2011
Name: XX Sex Reversal, Palmoplantar Keratoderma, and Squamous Cell Carcinoma
Mode of Inheritance: AR
Genes
RSPO1, mapped to 1p34.3
Tumor featuresskin cancer, squamous cell
Non-tumor featuresnails, absent palmoplantar hyperkeratosis XX(Sry-) sex reversal
Comment
Micali et al [1] and Radi et al[2] reported the details of a large inbred Sicilian family in which palmoplantar hyperkeratosis (PPK) and an associated predisposition to squamous cell carcinoma of the skin, segregated as an apparently recessive trait. All the PPK-affected members of the family were phenotypic males (46,XY or 46,XXsry-) while seven XX sibs were unaffected females. Linkage to Tylosis and Huriez syndrome loci was excluded[2]. Subsequently RSPO1 has been identified as the causative gene[3,4].
References
[1] Micali G, Nasca MR, Innocenzi D, Frasin LA, Radi O, Parma P, Camerino G, Schwartz RA. Association of palmoplantar keratoderma, cutaneous squamous cell carcinoma, dental anomalies, and hypogenitalism in four siblings with 46,XX karyotype: a new syndrome. J Am Acad Dermatol. 2005 Nov;53(5 Suppl 1):S234-9.
[2] Radi O, Parma P, Imbeaud S, Nasca MR, Uccellatore F, Maraschio P, Tiepolo L, Micali G, Camerino G. XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family. Am J Med Genet A. 2005 Oct 15;138A(3):241-6.
[3] Parma, P., Radi, O., Vidal, V., Chaboissier, M. C., Dellambra, E., Valentini, S., Guerra, L., Schedl, A., Camerino, G. R-spondin 1 is essential in sex determination, skin differentiation and malignancy. Nature Genet. 38: 1304-1309, 2006.
[4] Blaydon DC, Philpott MP, Kelsell DP. R-spondins in cutaneous biology: nails and cancer. Cell Cycle. 2007 Apr 15;6(8):895-7
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