Krystal Biotech - Decode DEB Sponsored Testing Program

EBS is the most common form and is characterized by fragility of the skin that results in blistering and erosions within the basal keratinocytes.¹ Clinical features range from localized blistering on the hands and feet to severe, widespread involvement that can include nail dystrophy and thickened skin on the palms and soles. While EBS is most commonly inherited in an autosomal dominant manner, in specific recessive subtypes, the disease may present with serious systemic complications such as muscular dystrophy, cardiomyopathy, or pyloric atresia.²

In DEB, skin cleavage occurs below the lamina densa of the basement membrane zone, occurring at the level of the anchoring fibrils.¹ The disorder is caused by mutations in the COL7A1 gene and can be inherited in either an autosomal dominant or autosomal recessive pattern. The severe recessive type can lead to debilitating complications such as fused fingers (pseudosyndactyly), joint contractures, esophageal strictures, and an increased risk of squamous cell carcinoma. In contrast, dominant and intermediate recessive forms typically present with milder symptoms, where blistering and scarring are more localized to the hands, feet, knees, and elbows.³

JEB is an autosomal recessive disorder where skin cleavage occurs through the lamina lucida of the basement membrane zone.¹ It is generally less common than the simplex or dystrophic types and is characterized by extreme fragility of the skin and mucous membranes, causing blisters to form after minimal trauma. In its generalized severe form, pervasive blistering is present from birth, and affected individuals often develop exuberant granulation tissue around the oral and nasal cavities. The generalized intermediate form typically presents with more localized blistering on the hands, feet, and knees, sometimes with associated renal or ureteral involvement. Additional common clinical features across subtypes include nail dystrophy, dental enamel defects, and scarring alopecia.⁴

KEB (formerly Kindler syndrome) is a rare autosomal recessive disorder with multiple levels of skin cleavage caused by mutations in the FERMT1 gene.¹ Clinical features typically begin at birth with blistering of the hands and feet, which later evolves into diffuse skin atrophy, photosensitivity, and poikiloderma (mottled skin pigmentation). Mucosal involvement is also common and can lead to serious complications such as gingivitis, periodontitis, and strictures in the esophagus or urinary tract. Long-term, patients are at a significantly increased risk for developing aggressive squamous cell carcinomas, particularly in mucosal areas.⁵