Epidermolysis Bullosa, Junctional with Muscular Dystrophy

NOW AVAILABLE! XomeDxSlice – EB

Using whole exome capture and sequencing, ALL of the known genes for the various forms of Epidermolysis Bullosa (Dystrophica, Simplex, Junctional) can be analyzed at one time, achieving substantial savings in both cost and time, with little loss of sensitivity. In most cases, this should now be the test of first choice for a new patient with the diagnosis of Epidermolysis Bullosa.

There are three variant phenotypic forms of EB due to plectin mutations; EB with pyloric atresia or pyloric stenosis (EB-PA), EB with muscular dystrophy (EB-MD), and a mild autosomal dominant EBS form known as EBS-Ogna. In all three forms, blistering begins in the neonatal period and continues throughout life. Blisters are usually generalized and may range from mild to severe. However, aside from blistering, the forms diverge based on the extracutaneous findings. EB-PA is often lethal in the newborn period; however surviving patients may show less severe blistering as they age. In these children pyloric atresia requires surgical intervention in the neonatal period. In EB-MD blistering is usually milder, and muscular dystrophy may appear in late childhood to adulthood. EBS-Ogna is a rare autosomal dominant variant of EB in which mutations on one allele have been described in extended family members. In all three of these variants that are caused by plectin mutations the tissue separation (blister) occurs just above the lamina lucida at the level of the hemidesmosome. Plectin staining of a skin biopsy may be reduced or absent consistent with plectin mutations. Muscle biopsies may also be stained for plectin in cases where MD is suspected and will show reduced or absent plectin staining. In rare cases, EB-PA was identified based on ultrasound abnormalities in fetuses of families with no family history. Subsequent molecular testing revealed the presence of ITGB4 or ITGA6 mutations, although this has not been described in EB cases with plectin defects.