Table 1.

GI manifestations and distress in ASD patients and animal models.

Gene	GI manifestation	GI distress	Study type	ENS phenotype	Reference
CHD8/chd8	Slow GI transit	Constipation and diarrhea	ASD patients, Danio rerio	50% reduction of enteric neurons in hindgut of chd8 morphants	Bernier et al. [7]
NOS1	Achalasia	Eating and drinking problems	ASD patients	Not analyzed	Shteyer et al. [8]
Nos1	Hypertensive and poorly relaxing lower esophageal sphincter	Eating and drinking problems	Nos −/− mice	Interstitial cells of Cajal impaired	Sivarao et al. [9]
Tcf4	Slow GI transit	Constipation	Tcf4 +/− mice Pitt–Hopkins mouse model	Not analyzed	Grubisic et al. [10]
Slc6a4 (Sert)	Slow GI transit, villus height and crypt depth decreased in mucosal structure	Constipation	Sert Ala56 mice	Reduced number of neurons in plexus of small and large intestines and TH, CGRP, or GABA positive neurons	Margolis et al. [12]
Foxp1	Achalasia, impaired relaxation of the lower esophageal sphincter, slow GI transit, reduced thickness of tunica muscularis in esophagus and colon	Eating and drinking problems, constipation	Foxp1 +/− mice	Not analyzed	Fröhlich et al. [11]
Nlgn3	Increased GI transit GABA-mediated alterations of colon motility	Diarrhea	NL3R451C mice	Hyperplasia in small intestine, dysregulation of GABAergic neurons	Hosie et al. [13]
NLGN3	Various GI complaints	Diarrhea poor bowel control, esophagitis, esophageal regurgitation, abdominal pain	ASD patients with NLGN3 p.R451C variant	Not analyzed	Hosie et al. [13]
Nlgn3	Faster colonic migrating motor complexes, increased colonic diameter	Not described, likely diarrhea	Nlgn3 −/− mice	No changes in ENS, inhibitory interneurons	Leembruggen et al. [14]
shank3a/shank3b	Slow GI transit, reduced peristalsis and motility, serotonin-positive enteroendocrine cells reduced	Constipation and/or diarrhea, reflux, cyclical vomiting	Danio rerio Phelan-McDermid syndrome (ASD) shank3abΔC+/−	No changes	James et al. [15]