Presentation: Neonate with skin blistering and fragility

A baby is born with extensive blisters all over his body. There are also multiple areas of missing skin. He develops new blisters with minimal friction during routine care. His parents are second cousins.

• Genomic testing should be considered in all neonates presenting with congenital blistering, and in older children with recurrent blistering at sites of friction, in collaboration with dermatologists at expert centres specialised in the care of epidermolysis bullosa (EB).
• Skin blistering may occur due to pathogenic variants in a range of genes that encode key proteins that form the basement membrane of the skin, such as collagen 7 (COL7A1). In some cases, skin fragility can be accompanied by hair anomalies and cardiac arrhythmias, as well as cardiomyopathy. These may be due to biallelic pathogenic variants in genes encoding components of desmosomes, including desmoplakin (DSP), desmocollins (DSC) and desmogleins (DSG). All of these genes are included in a panel (R164) as indicated below.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• There are four designated EB centres of excellence (highly specialised services) around the UK, and new patients and families should be referred to these centres to co-ordinate the care of suspected cases. They are:
  • Great Ormond Street Children’s Hospital in London (children);
  • Birmingham Women’s and Children’s Hospital (children);
  • Guy’s and St Thomas’ Hospital in London (adults); and
  • Solihull Hospital (adults).
• If EB is strongly suspected, the following test may be considered:
  • R164 Epidermolysis bullosa and congenital skin fragility: this currently tests for 47 genes, pathogenic variants in which are known to cause EB or skin blistering, including desmosomal components. It includes gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA).
• Copy number variants, short tandem repeats (STRs) and genes encoded by the mitochondrial genome may not be routinely included in the analysis if the panel is not delivered by whole genome sequencing. Please contact your Genomic Laboratory Hub with any specific queries.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
  

For clinicians

• DEBRA: NHS specialist EB healthcare
• GeneReviews: Dystrophic Epidermolysis Bullosa 
• GeneReviews: Epidermolysis Bullosa Simplex 
• National Organization for Rare Disorders: Epidermolysis bullosa
• NHS Health A to Z: Epidermolysis bullosa

For patients

• British Association of Dermatologists: Dystrophic epidermolysis bullosa
• DEBRA