Table 1.
Epidermolysis Bullosa Simplex and other diseases caused by mutations in Keratin 5 or Keratin 14
| EBS Variant # | Distinguishing Features # | Onset | Target Genes | Orig. Clinical Description |
|---|---|---|---|---|
| EBS, localized | Formerly known as “Weber-Cockayne”-type EBS. Blistering usually limited to hands and feet, but can occur at sites of repeated trauma; often associated with palmo-plantar keratoderma; worsens in warmer months | Infancy, early childhood, adulthood | Most frequently K5; Less frequently, K14 | F.P. Weber (1926) 1 E.A. Cockayne (1938) 2 |
| EBS, generalized | Formerly known as “Koebner”-type EBS. Blisters predominantly on hands and feet but blistering is often generalized; absence of large tonofilaments in basal keratinocytes on electron microscopy; worsens in warmer months | Birth or infancy | K5 (C-terminal region and L2 linker domain); K14 | H. Koebner (1886) 3 |
| EBS-DM (Dowling-Meara) | This form of EBS retained its original designation. Widespread and severe blistering; herpetiform and hemorrhagic blisters; frequent mucosal involvement; progressive palmoplantar keratoderma; nail dystrophy and milia; hyper- and hypo- pigmentation may occur; may improve with heat or fever | Birth | K5, K14 (at N- or C- terminal ends of the rod domain) | G.B. Dowling & R.H. Meara (1954) 4 |
| EBS-AR (autosomal recessive) | Very rare variant. Largely similar to the generalized form, though the frequency of blistering may be less. | Infancy | K14 | Hovnanian et al., (1993) provided the first mutation report. 5 |
| EBS-MP (with Mottled Pigmentation) | Skin blistering with mottled pigmentation of trunk and limbs; punctate palmo- plantar keratoderma; nail dystrophy. | Birth or infancy | K5 (Pro24->Leu mutation in head domain); K14 | T. Fischer & T. Gedde-Dahl (1979) 6 |
| EBS-MD (with Muscular Dystrophy) | EBS-like skin blistering with progressive limb-girdle muscular dystrophy. Very rare variant. | Infancy | Plectin | K.M Niemi et al. (1988) 7 |
| EBS-Migr (Migratory) | Formerly known as EBS with migratory circinate erythema. Annular migratory multiple erythema circinatum; multiple vesicles on the hands, feet, and legs; lesions heal with brown pigmentation but no scarring. Very rare variant. | Birth | K5 (tail domain) | L.H. Gu et al. (2003) 8 |
| DDD (Dowling-Degos Disease) | Reticular hyperpigmentation on flexure surfaces. | After puberty | K5 haploinsufficiency | G.B. Dowling and W. Freudenthal, (1938) 9 |
| NFJS (Naegeli-Franceschetti- Jadassohn) | Reticular hyper-pigmentation that disappears over time; hypohydrosis; palmoplantar keratoderma; absent fingerprint lines | Birth | K14 (head domain) | O. Naegeli (1927); A. Fransceschetti & W. Jadassohn (1954) 10 |
This table is adapted from Coulombe et al. (J. Clin. Invest. 119: 1784–93, 2009). Additional EBS subtypes, caused by mutations in genes other than K5 and K14, are more rare. See Fine et al. (J. Amer. Acad. Dermatol. 58:931–50, 2008) for a classification of all EBS variants.
References: 1) Weber, F.P. Proc. R Soc. Med. 19:72–5 (1926). 2) Cockayne, E.A. Br. J. Dermatol. 50:358–66 (1938). 3) Koebner, H. Dtsch. Med. Wochenschr. 12:21–22 (1886). 4) Dowling, G.B., and Meara, R.H. Br J Dermatol 66:139–143 (1954). 5) Hovnanian, A., Pollack, E., Hilal, L., Rochat, A., Prost, C., Barrandon, Y., Goossens, M. Nat Genet 3:327–332 (1993). 6) Fischer, T., Gedde-Dahl, T., Jr. Clin Genet 15:228–238 (1979). 7) Niemi, K. M., Sommer, H., Kero, M., Kanerva, L., Haltia, M. Arch Dermatol. 124:551–4 (1988). 8) Gu, L.H., Kim, S. C., Ichiki, Y., Park, J., Nagai, M., Kitajima, Y. J Invest Dermatol 121:482–485 (1983). 9) Dowling, G.B., Freudenthal, W. Br. J. Dermatol. 50:467–71 (1938). 10) Fransceschetti, A., Jadassohn, W. Dermatologica 108:1–28 (1954).