Genotype-phenotype correlations on epidermolysis bullosa with congenital absence of skin: A comprehensive review

Clin Genet. 2021 Jan;99(1):29-41. doi: 10.1111/cge.13792. Epub 2020 Jun 29.


Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype-phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype-phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch-like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non-collagenous interruptions of the triple-helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

Keywords: Bart syndrome; aplasia cutis; epidermolysis bullosa; genetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Substitution / genetics
  • Choanal Atresia / genetics*
  • Choanal Atresia / physiopathology
  • Ectodermal Dysplasia / genetics*
  • Ectodermal Dysplasia / physiopathology
  • Epidermolysis Bullosa Dystrophica / genetics*
  • Epidermolysis Bullosa Dystrophica / physiopathology
  • Gastric Outlet Obstruction / genetics*
  • Gastric Outlet Obstruction / pathology
  • Genetic Association Studies
  • Genotype
  • Humans
  • Mutation / genetics
  • Pylorus / abnormalities*
  • Pylorus / pathology
  • Skin / pathology
  • Skin Abnormalities / genetics*
  • Skin Abnormalities / pathology

Supplementary concepts

  • Aplasia cutis congenita of limbs recessive
  • Epidermolysis Bullosa With Congenital Localized Absence Of Skin And Deformity Of Nails
  • Pyloric Atresia