Figure 1The skin basement membrane zone and associated genetic diseases. Center: schematic representation showing the dermal-epidermal adhesion complex consisting of a number of structural proteins. Intracellular keratin filaments (keratin 5/14) bind to BPAG1 and plectin, which are ligands of hemidesmosomal transmembrane proteins collagen XVII and a6p4 integrin. These have binding sites for components of the basement membrane, such as laminin 5, laminin 5/6, laminin 10, nidogen, perlecan and collagen IV. Collagen VII is the major protein of the anchoring fibrils, which extend into the dermis and entrap dermal collagen and elastin fibers. Adherence of the basement membrane with the anchoring fibrils is secured by protein-protein interactions between collagen VII and laminin 5 and collagen IV. Different forms of hereditary EB are associated with defects in distinct components of the adhesion complex. (a) Electron microscopy shows intracellular disruption of basal keratinocytes in EB simplex (EBS). (b) Mechanically induced palmar blistering in EBS. (c) X-ray of pyloric atresia in a patient with JEB associated with pyloric atresia. (d) Trauma-induced skin blister in junctional EB (JEB). (e) Electron microscopy of intracellular disruption in basal keratinocytes in EBS. Note that in this case the cleavage plane is close to the hemidesmosomes. This form, often caused by defects in a6p4 integrin or plectin, has also been called hemidesmosomal EB (EBHD). (f) Non-scarring alopecia in JEB. (g) Scarring of the knees in mild dystrophic EB (DEB). (h) Electron microscopy shows tissue separation along the lamina lucida of the basement membrane in JEB. (i) Electron microscopy demonstrates sub-lamina densa blister formation in DEB. Note residual anchoring fibrils attached to the lamina densa in the roof of the blister. (j) Severe scarring and pseudosyndactyly of the toes in DEB. (k) Severe skin blistering and erosions in a newborn. On the basis of clinical appearance alone, it is not possible to recognize the subtype at this stage. Molecular tests, such as antigen mapping and mutation analysis, are required for precise diagnosis. EB, epidermolysis bullosa; JEB, junctional epidermolysis bullosa.