Dominant Dystrophic EB

Dominant dystrophic EB is transmitted as a dominant trait, while recessive dystrophic EB is a recessive disorder. In DDEB, only one parent also has DDEB. The affected parent has one abnormal copy of the involved collagen VII gene and one normal copy of the collagen VII gene (humans have two copies of most genes). With each pregnancy, there is a 50-50 chance that the abnormal gene will be passed along, resulting in a child with DDEB Likewise, there is a 50 percent chance that the normal gene will be passed to the child, resulting in a child who does not have EB (Figure 2).

Rarely, a child affected with DDEB may not have an affected parent; this is known as a de novo mutation, which means that the mutation occurred in the egg or sperm before fertilization and is not carried by either parent. RDEB is transmitted in an autosomal recessive form, in which both parents are normal without any manifestations of EB; however, each carries an abnormal copy of the keratin gene. In this instance, there is a 25 percent chance that the child will inherit both abnormal collagen VII genes, in which case the child will be affected.

In dominant dystrophic EB, blistering may be present at birth and may be widespread, as is seen in generalized DDEB, or blistering may occur mostly on the hands and feet in acral DDEB. Congenital localized absence of skin (also called aplasia cutis congenita or Bart’s syndrome) may be present at birth. Other variants include pretibial DDEB, where blisters occur predominantly on the hands, feet, nails and lower legs and develop at birth or during infancy; DDEB with nail dystrophy only, which presents at birth or during infancy; and DDEB pruriginosa, which presents during childhood with either widespread, generalized blisters or with more localized blistering of the hands and feet in association with severe pruritus (itching) and nail dystrophy. In all form of dystrophic EB, scarring, nail dystrophy and milia are common. Granulation tissue is not seen. Poor dental enamel and oral erosions are not seen, although increased frequency of dental caries and constipation are reported with pretibial DEB. Poor growth, anemia, and blistering and other problems involving the trachea/respiratory tract, intestines/gastrointestinal tract, eyes or genitourinary tract are not seen. Pseudosyndactyly does not occur.

The risk of skin cancer is not increased in association with DEB with the exception of DEB pruriginosa, in which squamous cell carcinoma of the skin has been reported to occur after 30 years of age. A rare variant, DEB-bullous dermolysis of the newborn (DEB-BDN), presents at birth or during infancy with generalized blistering. Milia, scarring and nail dystrophy are common, as are dental caries. In some children with DEB-BDN, blistering stops in infancy.