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Eur J Hum Genet. Jul 2009; 17(7): 881–882.
Published online Apr 1, 2009. doi:  10.1038/ejhg.2009.55
PMCID: PMC2986492
Angioma serpiginosum is not caused by PORCN mutations
Rudolf Happle1*
1Department of Dermatology, Philipp University of Marburg, Marburg, Germany
*Department of Dermatology, Phillipp University of Marburg, Margurg, Germany. Tel: 49 6421 586 2908; Fax: 49 6421 586 2898; E-mail: happle/at/med.uni-marburg.de
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.
  • Blinkenberg EO, Brendehaug A, Sandvik AK, Vatne O, Hennekam RC, Houge G. Angioma serpiginosum with oesophageal papillomatosis is an X-linked dominant condition that maps to Xp11.3-Xq12. Eur J Hum Genet. 2007;15:543–547. [PubMed]
  • 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]
  • Gorlin RJ, Meskin LH, Peterson WC, Jr, Goltz RW. Focal dermal hypoplasia syndrome. Acta Dermatol Venereol. 1963;43:421–440. [PubMed]
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  • Chen W, Liu TJ, Yang YC, Happle R. Angioma serpiginosum arranged in a systematized segmental pattern suggesting mosaicism. Dermatology. 2006;213:236–238. [PubMed]
  • 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]
  • Zala L, Ettlin C, Krebs A. Fokale dermale Hypoplasie mit Keratokonus, Ösophaguspapillomen und Hidrokystomen. Dermatologica. 1975;150:176–185. [PubMed]
  • Brinson RR, Schuman BM, Mills LR, Thigpen S, Freedman S. Multiple squamous papillomas of the esophagus associated with Goltz syndrome. Am J Gastroenterol. 1987;82:1177–1179. [PubMed]
  • 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]
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