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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 21, 2015; 21(43): 12296-12310
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12296
Table 1 Genes involved in the phenotype of monogenic very early onset of inflammatory bowel disease
GeneInheritanceChrOMIMDiseaseClinical Features IBD-likeTreatmentRef.
Hyper and autoinflammatory disorders
MVKAR12q24#260920Mevalonate kinase deficiencyAbdominal pain, Diarrhea, vomitingAnakinra[28,30-32]
MEFVAR16p13#134610 #249100Familial Mediterranean FeverDiarrhea, abdominal pain, mucus in the stool, peritonitisColchicine[33,34]
PLCG2AD16q23#614878Autoinflammation, antibody deficiency, and immune dysregulation syndromeBloody diarrhoea, UC, enterocolitis[35]
NLRP12AD19q13#611762Familial cold autoinflammatory syndrome 2Abdominal painAnakinra[37]
NLRC4AD2p22#616050Autoinflammation with infantile enterocolitisNeonatal-onset enterocolitisAnakinra[38-40]
Immune regulation and dysregulation disorders (innate and adaptive immune responses)
XIAPXLXq25#300635X-linked lymphoproliferative syndrome 2Perianal abscessesHSCT[41-44]
STXBP2AR19p13#613101Familial haemophagocytic lymphohistiocytosis type 5IDB-like colitisHSCT[45]
HPS1AR10q23#203300Hermansky Pudlak syndrome (type 1, 4 and 6)IBD, UC, Granulomatous colitisPlatelet transfusion Anakinra[46-50]
HPS422q12#614073Granulomatous colitisInfliximab
HPS610q24#614075Gastrointestinal symptoms, granulomatous colitis, imperforate anus, gluteal flap repairsSubtotal colectomy
FOXP3XLXp11#304790Immunodysregulation, polyendocrinopathy and enteropathyIntractable diarrhea, total or subtotal intestinal villous atrophy, enteropathyHSCT[51]
AIREAR/AD21q22#240300Autoimmune Polyendocrinopathy Candidiasis Ectodermal DystrophyMalabsorption, diarrhea, chronic atrophic gastritisNo specific treatment is available[52]
IL101q32*124092IL-10 Signaling defectsSevere early-onset enterocolitis
IL10RAAR11q23#613148Inflammatory Bowel Disease-28, early onsetEarly onset enterocolitis, enteric fistula, perianal abscessesHSCT[53-63]
IL10RBAR21q22#612567Inflammatory Bowel Disease-25, early onsetEarly onset enterocolitis, perianal abscesses, enterocutaneous and rectovaginal fistula
Defects in phagocyte bacterial killing and neutropenia
SLC37A4GSD-1bAR11q23#232220Glycogen storage disease 1bPerioral and perianal lesions, ileitis, colitis, CD-like, protuberant abdomenGranulocyte colony stimulating factor, prophylactic oral iron[64-66]
G6PC3AR17q21#612541Severe Congenital neutropenia 4Diarrhea, colitis, abdominal pain, perianal fistula or abscess, CD-like, oral aphthous ulcerationGranulocyte colony stimulating factor[67]
ITGB2AR21q22#116920Leucocyte adhesion deficiency 1CD-like with discontinuous stomatitis, ileocolitis, perianal and rectal abscess, fistulas, adhesion, stricturesHSCT[70,71]
NCF1AR7q11#233700Chronic granulomatousColitis, perirectal abscessHSCT[70-75]
NCF2AR1q25#233710diseasePerirectal abscesses due to immunodeficiency
NCF4AR22q12#613960Chronic granulomatous colitis, diarrhea perianal infections, erosions and ulceration of the gastric fundus and colonic mucosa, multiple small granulomata on colonic biopsy.
CYBAAR16q24#233690Perirectal abscesses due to immunodeficiency
CYBBXLXp11#306400Gastrointestinal perirectal abscesses due to immunodeficiency, enteritis and colitis
T and B lymphocyte selection activation defects
WASXLXp11#301000Wiskott-Aldrich SyndromeDiarrhea, hematemesis and melena IBD, UC like, colonic inflammation with crypt abscessHSCT/transfusion of autologous genetically modified[77-79]
DCLRE1CAR10p13#603554 #602450Omenn Syndrome; Athabascan-type severe combined immunodeficiencyChronic diarrheaHSCT[25,80-82,85,86]
RAG1AR11p124Omenn Syndrome
RAG2AR#603554
LIG4AR13q33#606593LIG4 SyndromeProtracted diarrheaHSCT
ADAAR20q13#102700Partial adenosine deaminase deficiencyEnzyme replacement therapy using frozen irradiated red blood cells/HSCTHSCT
IL2RGXLXq13#300400 #312863Severe Combined Immunodeficiency; Moderate Immunodeficiency
CD3GAR11q23#615607Immunodeficiency 17Diarrhea autoimune, gastroenteritis, recurrent, enteropathyHSCT
ZAP70AR2q11#269840Selective T-cell defectDiarrheaHSCT
LCKAR1p35#615758Immunodeficiency 22Darrhea autoimmune, panniculiteHSCT[83,84]
LRBAAR4q31#614700Common variable immunodeficiency 8Colitis, IBDIg replacement therapy/HSCT[88,90,91]
ICOSAR2q33#607594Common variable immunodeficiency 1Early onset gastrointestinal tract infections, enteritis, recurrent diarrheaIg replacement therapy/ HSCT[92]
IL21AR4q27# 615767IL-21 deficiencyEarly onset IBDIg replacement therapy/HSCT[93]
CTLA-4AD2q33#616100Autoimmune lymphoproliferative syndrome type VEarly onset IBD and autoimmunityNo specific treatment is available[122]
TNFRSF13BAR/AD17p11#240500TACI deficiencyEnteritis, recurrent diarrheaIg replacement therapy/HSCT[94]
COG6AR13q14#614576Congenital disorder of glycosylation, type IIIAnal anteposition, recurrent diarrhea, IBDNo specific treatment is available[123]
BTKXLXq22#300755 #307200Agammaglobulinemia Isolates growth hormone deficiency type IIIDiarrheaIg replacement therapy/HSCT[99,100]
PIK3R1AR5q13#615214Agammaglobulinemia 7Recurrent gastroenteritis[101]
CD40LGXLXq26#308230Immunodeficiency with hyper-IgM type IDiarrhea[96,97]
AICDAAR12p13#605258Immunodeficiency with hyper-IgM type IIGastrointestinal tract infections[98]
Disorder of apoptosis
CASP8AR2q33#607271Caspase 8 deficiencychronic diarrheaNo specific treatment is available[102]
ITCHAR20q11#613385Autoimmune disease, multisystem with facial dysmorphismEnteropathy, chronic diarrhea, malabsorption, gastrostomy tube feedingImmunosuppressive treatment[112]
MASP2AR1p36#613791MASP2 deficiencyIBD, UC-like[113]
WELL defined syndromes associated with EO-IBD
TTC7AAR2p21#243150Multiple intestinal atresiaMultiple areas of atresia along the small and large intestines, Intestinal malrotation Intraluminal calcification, bowel distention Mucous membrane ulcerationSurgery[103-105]
TTC37AR5q15#222470Trico hepato enteric syndromeDiarrhea, severe villous atrophyParenteral nutrition[107,108]
SKIV2LAR6p21#614602Trico hepato enteric syndrome 2Diarrhea, colitis, severe and intractable villous atrophyIg supplementation[106]
NEMO/IKBKGXLXq28*300248X-linked ectodermal dysplasia and immunodeficiencyCD-like colitis, villous atrophy, recurrent digestive tract infections, intractable diarrhea and recurrent ulcerationsHSCT[109,110]
GUCY2CAD12p13#614616Familial DiarrheaEarly onset chronic diarrhea, IBD, CD, small-bowel obstruction, esophagitis, irritable bowel syndrome, ileal inflammation, abdominal painParenteral nutrition[111]
Defects affecting the integrity of intestinal barrier
COL7A1AR3p21#226600Dystrophic epidermolysis bullosaGastrointestinal complications, diarrhea, colitis, esophageal blisters strictures, anal blisters, constipationImmuno myeloablative chemotherapy and allogenic HSCT[114]
ADAM17AR2p25#614328Neonatal inflammatory skin and bowel disease 1Perioral and perianal erythemas with fissuring, diarrhea, malabsorption, plasma cell duodenitis crypt hyperplasia, villous atrophyEGFR Ligands[115]
FERMT1/KIND1AR20p12#173650Kindley syndromeIntestinal involvement with haemorrhagic diarrhoea, UCNo specific treatment is available[116]
EGFRAR7p11#616069Neonatal inflammatory skin and bowel disease 2DiarrheaNo specific treatment is available[117,118]
TGFBR1AD9q22#609192Loeys-Dietz syndrome, type 1Gastrointestinal disorders,Medication and preventative surgery[119]
TGFBR2AD3p24#610168Loeys-Dietz syndrome, type 2