FaCD Online Syndrome Fact Sheet

Last updated: 07 Aug 2008

Co-authors of this topic: Peter van den Akker, M.D., Dept of Genetics UMC Groningen, the Netherlands

Name: Inherited Epidermolysis Bullosa

Synonym: incl. EB Simplex (EBS), Junctional EB (JEB), Dystophic EB (DEB, Recessive DEB, RDEB, Hallopeau-Siemens, dominant DEB, DDEB) and subtypes

Mode of Inheritance: AD/AR

Tumor features

esophagus, squamous cell cancer of the
intraoral squamous cell cancer
melanoma, cutaneous
skin cancer, basal cell
skin cancer, squamous cell

Tumor features (possible)

angiosarcoma
atypical teratoid/rhabdoid tumor of the CNS
keratoacanthoma
osteosarcoma

Non-tumor features

anal blistering
blistering of conjunctivae
blistering of cornea
blistering of the skin
esophageal blistering
intraoral blistering

Comment

This group of disorders is characterized by blistering of the skin and, depending on subtypes, mucosa in particular that of oropharynx and esophagus. Many subtypes have been defined.[1]. Skin cancer is a recognized complication of EB[2,8].

Squamous cell cancer (SCC) has been observed in EB Simplex (after 35 years, cumulative risk 1.4% risk at age 60 years) and is the most important cause of death in RDEB-severely generalized type (77% SCC risk at age 60). Risks for milder DEB types are smaller (27% for RDEB-generalized other; 3.9% for DDEB). SCC in EB generally involves the skin, but in RDEB intraoral and esophageal SCC has been reported as well.[2]. It is important to note that increased risk of developing SCC starts in teenage years[8]. SCC risk in JEB is generally thought not to be increased although some authors have suggested otherwise[6,7].

Basal cell cancer (BCC) in EB is generally not seen before the age of 40 years, but has been diagnosed at age 25 in cases of DDEB. Cumulative BCC risks are 4.5% for EBS-localized and 16.3% for the other EBS variants taken together with the largest contribution from EBS Dowling-Meara subtype; 4.4% for RDEB-generalized other and 3.2% for DDEB. No increased BCC risk has been observed for RDEB-severely generalized and JEB.[2].

Melanoma risk and age at diagnosis depends on EB subtype. Cumulative risks for EBS-localized and other EBS subtypes is 1.8% with melanoma generally observed after 55 years in the localized subtype and after 35 years in the other EBS types. Melanomas in RDEB occur relatively early and have been observed in children. Cumulative risk for the RDEB-severely generalized subtype is 2.5% and 0.7% for RDEB-generalized other. In DDEB, melanomas have been observed at age 25 years and older with cumulative risk of 2.1%. No increased melanoma risk has been observed for JEB.[2].

A few other tumor types have been reported incidentally: osteosarcoma, and angiosarcoma in DEB[3,4] and a congenital cerebellar malignant rhabdoid tumor[5] and multiple keratoacathomas[9] in JEB.

The different genes involved in EB are not listed separately in this file; please consult the OMIM links given above for more information.

Links

DEBRA International 18 1 08

References

[1] Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, McGrath JA, Mellerio JE, Murrell DF, Shimizu H, Uitto J, Vahlquist A, Woodley D, Zambruno G. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. Journal of the American Academy of Dermatology 2008; 58(6):931-50.
[2] Fine JD, Johnson LB, Suchindran C, Bauer EA, Carter DM, McGuire J, Lin A, Stern R, Nall L, Moshell A. Cancer and Inherited Epidermolysis Bullosa. In: Fine JD, Bauer EA, McGuire J, Moshell A, editors. Epidermolysis Bullosa; Clinical, Epidemiologic, and Laboratory Advances and the Findings of the National Epidermolysis Bullosa Registry. 1 ed. Baltimore: The John Hopkins University Press; 1999. p. 175-192
[3] Yamauchi Y, Takahashi K, Shiotsu H. Osteogenic sarcoma of the tibia in a patient with epidermolysis bullosa dystrophica. Clinical orthopaedics and related research 1988;(228):273-7.
[4] Schmutz JL, Kue E, Baylac F, Reichert-Penetrat S, Barbaud A. Angiosarcoma complicating Hallopeau-Siemens-type hereditary epidermolysis bullosa. The British journal of dermatology 1998; 138(5):910-2.
[5] Krous HF, Chadwick AE, Haas EA, Breisch E, Masoumi H. Congenital cerebellar malignant rhabdoid tumor in an infant with junctional epidermolysis bullosa. Pediatric and developmental pathology 2007 Nov-Dec; 10(6):481-6.
[6] Mallipeddi R, Keane FM, McGrath JA, Mayou BJ, Eady RA. Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa. Journal of the European Academy of Dermatology and Venereology : JEADV 2004; 18(5):521-6.
[7] Weber F, Bauer JW, Sepp N, Högler W, Salmhofer W, Hintner H, Fritsch P. Squamous cell carcinoma in junctional and dystrophic epidermolysis bullosa. Acta dermato-venereologica 2001 Jun-Jul; 81(3):189-92.
[8] Mallipeddi R. Epidermolysis bullosa and cancer. Clinical and experimental dermatology 2002; 27(8):616-23.
[9] Pellicano R, Fabrizi G, Cerimele D. Multiple keratoacanthomas and junctional epidermolysis bullosa. A therapeutic conundrum. Archives of dermatology 1990; 126(3):305-6.