IllnessIPEX syndrome, differential diagnosis

NGS +

IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) mainly affects males. It is caused by dysfunctions of the immune system via attacking tissues and organs of the own organism. IPEX syndrome is characterized by the development of multiple autoimmune disorders in affected individuals, particularly autoimmune enteropathy with severe diarrhea as the first symptom, dermatitis and polyendocrinopathy (type 1 diabetes mellitus, hyperthyroidism, anemia, thrombocytopenia or neutropenia). IPEX syndrome can be life-threatening in early childhood. Mutations in the FOXP3 gene cause this syndrome. The encoded protein is essential for the production and normal function of regulatory T lymphocytes. IPEX syndrome is inherited in an X-linked recessive manner. Regarding the narrower differential diagnosis, at least 9 other guideline-curated IPEX-like syndromes are inherited predominantly in an autosomal recessive manner or rarely in an autosomal dominant or X-linked manner. In total, >30 genes are considered for differential diagnostic purposes. Due to its rare occurrence, the molecular genetic diagnostic yield of IPEX syndrome is currently unknown. Therefore, a negative DNA test result by no means excludes the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1118/

• Alias: Autoimmune enteropathy type 1
• Alias: Autoimmunity-immunodeficiency syndrome, XL
• Alias: Diabetes mellitus, congenital insulin-dependent, with fatal secretory diarrhea
• Alias: Diarrhea, polyendocinopathy, fatal infection syndrome, XL
• Alias: Enteropathy, autoimmune, with hemolytiv anemia + polyendocrinopathy
• Alias: IDDM-secretory diarrhea syndrome
• Alias: Insulin-dependent diabetes mellitus secretory diarrhea syndrome
• Alias: Polyendocrinopathy, immune dysfunction + diarrhea, XL; XPID
• Alias: XL autoimmunity-allergic dysregulation syndrome
• Allelic: Atrial septal defect 9 (GATA6)
• Allelic: Atrioventricular septal defect 5 (GATA6)
• Allelic: Celiac disease, susceptibility to, 3 (CTLA4)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 8 (EPCAM)
• Allelic: Diabetes mellitus, insulin-dependent, 12 (CTLA4)
• Allelic: Diabetes mellitus, noninsulin-dependent, late onset (GCK)
• Allelic: Diabetes mellitus, transient neonatal 2 (ABCC8)
• Allelic: Diabetes mellitus, transient neonatal 3 (KCNJ11)
• Allelic: Diabetes mellitus, type 2, susceptibility to (KCNJ11)
• Allelic: Diabetes mellitus, type II, susceptibility to (PDX1)
• Allelic: Diabetes, mellitus, insulin-dependent, susceptibility to, 10 (IL2RA)
• Allelic: Hashimoto thyroiditis (CTLA4)
• Allelic: Hepatitis B virus, susceptibility to (IL10RB)
• Allelic: Lung cancer, susceptibility to FASLG)
• Allelic: MODY, type II (GCK)
• Allelic: MODY, type IV (PDX1)
• Allelic: Maturity-onset diabetes of the young, type 10 (INS)
• Allelic: Maturity-onset diabetes of the young, type 13 (KCNJ11)
• Allelic: Persistent truncus arteriosus (GATA6)
• Allelic: Systemic lupus erythematosus, susceptibility to (CTLA4)
• Allelic: Tetralogy of Fallot (GATA6)
• Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Autoimmune disease, multisystem, with facial dysmorphism (ITCH)
• Autoimmune lymphoproliferative syndrome, type IA (FAS)
• Autoimmune lymphoproliferative syndrome, type IB (FASLG)
• Autoimmune lymphoproliferative syndrome, type II (CASP10)
• Autoimmune polyendocrinopathy syndrome , type I, with/-out reversible metaphyseal dysplasia (AIRE)
• Combined cellular + humoral immune defects with granulomas (RAG1, RAG2)
• Diabetes mellitus, insulin-dependent, 2 (INS)
• Diabetes mellitus, noninsulin-dependent (ABCC8)
• Diabetes mellitus, permanent neonatal 1 (GCK)
• Diabetes mellitus, permanent neonatal 3, with/-out neurologic features (ABCC8)
• Diabetes mellitus, permanent neonatal 4 (INS)
• Diabetes, permanent neonatal 2, with/-out neurologic features (KCNJ11)
• Diarrhea 2, with microvillus atrophy (MYO5B)
• Diarrhea 5, with tufting enteropathy, congenital (EPCAM)
• Gastrointestinal defects + immunodeficiency syndrome (TTC7A)
• Growth hormone insensitivity with immune dysregulation 1, AR (STAT5B)
• Growth hormone insensitivity with immune dysregulation 2, AD (STAT5B)
• Hyper-IgE recurrent infection syndrome (STAT3)
• Hyper-IgE recurrent infection syndrome, AR (DOCK8)
• Hyperinsulinemic hypoglycemia, familial, 1 (ABCC8)
• Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
• Hyperinsulinemic hypoglycemia, familial, 3 (GCK)
• Hyperproinsulinemia (INS)
• Hypoglycemia of infancy, leucine-sensitive (ABCC8)
• IDDM-Secretory diarrhea syndrome; DMSD
• Immune dysregulation with autoimmunity, immunodeficiency + lymphoproliferation (CTLA4)
• Immune dysregulation-polyendocrinopathy-enteropathy-XL syndrome (FOXP3)
• Immunodeficiency 12 (MALT1)
• Immunodeficiency 31A, mycobacteriosis, AD (STAT1)
• Immunodeficiency 31B, mycobacterial + viral infections, AR (STAT1)
• Immunodeficiency 31C, chronic mucocutaneous candidiasis, AD (STAT1)
• Immunodeficiency 41 with lymphoproliferation + autoimmunity (IL2RA)
• Immunodeficiency 60 (BACH2)
• Immunodeficiency, common variable, 8, with autoimmunity (LRBA)
• Immunodysregulation, polyendocrinopathy, enteropathy, XL (FOXP3)
• Inflammatory bowel disease 25, early onset, (IL10RB)
• Inflammatory bowel disease 28, early onset, AR (IL10RA)
• Neutropenia, severe congenital, XL (WAS)
• Omenn syndrome (DCLRE1C, RAG1, RAG2)
• Pancreatic + cerebellar agenesis (PTF1A)
• Pancreatic agenesis + congenital heart defects (GATA6)
• Pancreatic agenesis 1 (PDX1)
• Pancreatic agenesis 2 (PTF1A)
• Severe combined immunodeficiency, Athabascan type (DCLRE1C)
• Severe combined immunodeficiency, B cell-negative (RAG1, RAG2)
• Thrombocytopenia, XL (WAS)
• Thrombocytopenia, XL, intermittent (WAS)
• Trichohepatoenteric syndrome 1 (TTC37)
• Trichohepatoenteric syndrome 2 (SKIV2L)
• Wiskott-Aldrich syndrome (WAS)
• a/b T-cell lymphopenia + g/d T-cell expansion, severe cytomegalovirus infection, autoimmunity (RAG1)