Table 2.

Mendelian diseases associated with EoE

Mendelian disease associated with EoE	Genetic mutation	Plausible etiologic mechanism
Loeys-Dietz syndrome (LDS)	Mutations in transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2, respectively)	Enhanced transforming growth factor beta (TGF-β) signaling
Ehlers-Danlos syndrome, hypermobility type	Unknown—other subtypes of Ehlers-Danlos syndrome are caused by mutations in collagen genes	Disrupted joint and skin development; increased activity of TGF-β due to altered binding by extracellular matrix
Severe atopy syndrome associated with metabolic wasting (SAM syndrome)	Homozygous mutations in desmoglein 1 (DSG1)	Disrupted epithelial barrier
Netherton’s syndrome	Loss-of-function mutations in skin protease inhibitor, kazal type 5 (SPINK5)	Unrestricted protease activity of kallikrein 5 and 7 (KLK5, KLK7)
PTEN hamartoma tumor syndrome (PHTS)	Mutations in phosphatase and tensin homolog (PTEN)	Inhibited regulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathway
Autosomal dominant hyper-IgE syndrome	Deleterious mutations in signal transducer and activator of transcription 3 (STAT3)	Dysregulated response to IL-6 and possibly IL-5
Autosomal recessive form of hyper-IgE syndrome	Loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8)	Loss of T-cell homeostasis; lack of durable secondary antibody response against specific antigens