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Eur J Hum Genet. 2009 July; 17(7): 881–882.
Published online 2009 April 1. doi:  10.1038/ejhg.2009.55
PMCID: PMC2986492

Angioma serpiginosum is not caused by PORCN mutations

In 2007, Blinkenberg et al1 described ‘angioma serpiginosum' in a four-generation family and assigned the underlying gene locus to Xp11.3–Xq12. Subsequently, Houge et al2 documented a deletion containing PORCN gene in the affected individuals and argued that this gene ‘may also cause angioma serpiginosum'. With regard to this diagnosis, however, I would like to raise my voice of polite dissent.

My diagnosis is focal dermal hypoplasia (FDH). On higher magnification the erythematous skin lesions, as photographically documented by Blinkenberg et al,1 are found to be intermingled with small patches of dermal hypoplasia or atrophy. This feature is not compatible with angioma serpiginosum (AS), but is highly suggestive of FDH. A biopsy obtained from such areas would certainly have shown a rather thin dermis and thus would have helped to distinguish this skin disorder from AS. On the other hand, dilated capillaries located in the papillae and in the uppermost part of the dermis, as noted by Blinkenberg et al,1 cannot be taken as a distinguishing feature of AS, because such signs of telangiectasia do likewise occur in FDH.3, 4, 5, 6

The proposed diagnosis would imply that no member of this family had AS. In contrast to FDH, AS is not associated, according to the present knowledge, with major extracutaneous anomalies. AS is often arranged in an asymmetric or otherwise segmental distribution, which, on rare occasions, may even be reminiscent of Blaschko's lines, but such cases have so far always been sporadic.7 In familial cases of AS, the involvement is rather symmetric and nonsegmental.7 So far, there is not the slightest indication that AS can be inherited as an X-linked trait.

For the following reasons I propose to exclude the diagnosis of AS in the family described by Blinkenberg et al:1 (i) Some patients had nail dysplasia and bald patches involving the scalp, which are characteristic signs of FDH but unknown in AS.8 (ii) Esophageal or hypopharyngeal papillomatosis is a typical feature of FDH,9, 10, 11 but absent in AS. (iii) An X-linked transmission limited to females is characteristic of FDH but not compatible with AS that is most likely caused by an autosomal gene.7 (iv) When AS shows a mosaic arrangement, a familial occurrence has so far never been reported.7

Therefore, the statement of Houge et al2 that their patients had ‘angioma serpiginosum, a cosmetic skin disease' does not seem to be correct. In my view, AS cannot be considered as ‘a mild variant of Goltz–Gorlin syndrome', as suggested by Blinkenberg et al.1 On the contrary, skin lesions, as documented in this family, were part of a potentially serious multisystem birth defect in the form of FDH. Perhaps, a thorough examination of the bones by imaging techniques would have revealed additional features of this syndrome. This is not merely a theoretical issue because in this family genetic counseling may be affected by an incorrect diagnosis of AS. After all,one cannot predict the severity of the manifestation of FDH in the next generation.

In conclusion, I fear that according to the present knowledge, a search for PORCN mutations in patients with AS would yield completely negative results.


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  • Houge G, Oeffner F, Grzeschik KH. An Xp11.23 deletion containing PORCN may also cause angioma serpiginosum, a cosmetic skin disease associated with extreme skewing of X-inactivation. Eur J Hum Genet. 2008;16:1027–1028. [PubMed]
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  • Grzeschik KH, Bornholdt D, Oeffner F, et al. Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nat Genet. 2007;3:833–835. [PubMed]
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  • Gordjani N, Herdeg S, Ross UH, Grimme H, Kleinschmidt M, Brandis M. Focal dermal hypoplasia (Goltz-Gorlin syndrome) associated with obstructive papillomatosis of the larynx and hypopharynx. Eur J Dermatol. 1999;9:618–620. [PubMed]

Articles from European Journal of Human Genetics are provided here courtesy of Nature Publishing Group