The Diagnostic Approach to Monogenic Very Early Onset XXXX .

@entity1 @entity32 @entity31 @entity29 @entity8787 @entity74 @entity688 @entity30
@entity1 with a diverse spectrum of rare @entity74 can present with @entity29 ( @entity8787 ). @entity1 with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of @entity30 , @entity31 , or @entity8787 unclassified. Defects in @entity688 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal @entity32 . Several @entity74 that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the @entity8787 -like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of @entity8787 . Genetic analysis is required to identify the cause of the disorder and offer the @entity1 appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of @entity1 . We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with @entity8787 -like intestinal @entity32 . In addition, we provide approaches for identifying @entity1 likely to have these disorders. We also discuss classic approaches to identify these variants in @entity1 , starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of @entity74 .
