FaCD Online Syndrome Fact Sheet

Last updated: 29 Jul 2011

Name: XX Sex Reversal, Palmoplantar Keratoderma, and Squamous Cell Carcinoma

Mode of Inheritance: AR

OMIM number: 610644  

Genes

RSPO1, mapped to 1p34.3

Tumor features

skin cancer, squamous cell

Non-tumor features

nails, 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