title: A practical guide for the diagnosis of primary enteric nervous system disorders.
abstract: OBJECTIVE
  Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field.
  
  
  RESULTS
  Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance.
  
  
  CONCLUSIONS
  The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.
authors.affiliation: Pediatric Center, Clinique des Grangettes, and Centre Médical Universitaire, Geneva, Switzerland
authors.forename: M G
authors.initials: MG
authors.lastname: Schäppi
authors.forename: A
authors.initials: A
authors.lastname: Staiano
authors.forename: P J
authors.initials: PJ
authors.lastname: Milla
authors.forename: V V
authors.initials: VV
authors.lastname: Smith
authors.forename: J A
authors.initials: JA
authors.lastname: Dias
authors.forename: R
authors.initials: R
authors.lastname: Heuschkel
authors.forename: S
authors.initials: S
authors.lastname: Husby
authors.forename: M L
authors.initials: ML
authors.lastname: Mearin
authors.forename: A
authors.initials: A
authors.lastname: Papadopoulou
authors.forename: F M
authors.initials: FM
authors.lastname: Ruemmele
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vandenplas
authors.forename: S
authors.initials: S
authors.lastname: Koletzko
mesh_terms: D000293:Adolescent; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000151:congenital / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D032921:Consensus; D004065:Digestive System Abnormalities / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D004067:Digestive System Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D017615:Enteric Nervous System / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D005729:Ganglioneuroma / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D005762:Gastroenterology / Q000379:methods; D005767:Gastrointestinal Diseases / Q000151:congenital / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000002:abnormalities / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D018814:Multiple Endocrine Neoplasia Type 2b / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D010372:Pediatrics / Q000379:methods; D017410:Practice Guidelines as Topic