IllnessDiabetes mellitus, MODY; differential diagnosis

NGS +

[Sanger]

MODY is the most common form of monogenic diabetes. The clinical features of MODY vary according to genetic aetiology. Most common subtypes are HNF1A-MODY (30-50%), GCK-MODY (30-50%), HNF4A-MODY (10%) and HNF1B-MODY (1-5%). The latter is also known as kidney cysts and diabetes syndrome. At least nine other less common genetic subtypes have been described. Patients with HNF1A and HNF4A mutations have slowly progressive beta cell dysfunction. Vascular complications of diabetes are observed with a similar frequency to type 1 or type 2 diabetes. GCK-associated MODY is characterised by asymptomatic, non-progressive mild fasting hyperglycaemia with low postprandial glucose excursions from birth and is not associated with vascular complications. Indications for genetic testing for MODY include the occurrence of diabetes in adolescence or young adulthood, maintenance of endogenous insulin production and usually a significant family history of diabetes. Inheritance is usually autosomal dominant; penetrance values vary according to mutated genes.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK500456/

• APPL1, BLK, KLF11, PAX4: evidence for causing MODY needs to be expanded/confirmed
• Allelic: Allelic: Ventricular septal defect 1 (GATA4)
• Allelic: Aniridia (PAX6)
• Allelic: Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Allelic: Atrial septal defect 2 (GATA4)
• Allelic: Atrial septal defect 9 (GATA6)
• Allelic: Atrioventricular septal defect 4 (GATA4)
• Allelic: Atrioventricular septal defect 5 (GATA6)
• Allelic: Cardiomyopathy, dilated, 1A (LMNA)
• Allelic: Carotid intimal medial thickness 1 (PPARG)
• Allelic: Cataract 41 (WFS1)
• Allelic: Cataract with late-onset corneal dystrophy (PAX6)
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Coloboma of optic nerve (PAX6)
• Allelic: Coloboma, ocular (PAX6)
• Allelic: Colorectal cancer, susceptibility to, 10 (POLD1)
• Allelic: Deafness, AD 6/14/38 (WFS1)
• Allelic: Diabetes mellitus, insulin-dependent (HNF1A)
• Allelic: Diabetes mellitus, insulin-dependent, 20 (HNF1A)
• Allelic: Diabetes mellitus, ketosis-prone, susceptibility to (PAX4)
• Allelic: Diabetes mellitus, noninsulin-dependent (ABCC8, HNF1B, HNF4A)
• Allelic: Diabetes mellitus, noninsulin-dependent, 2 (HNF1A)
• Allelic: Diabetes mellitus, noninsulin-dependent, late onset (GCK)
• Allelic: Diabetes mellitus, permanent neonatal (ABCC8, GCK, INS)
• Allelic: Diabetes mellitus, permanent neonatal, with neurologic features (KCNJ11)
• Allelic: Diabetes mellitus, transient neonatal 2 (ABCC8)
• Allelic: Diabetes mellitus, transient neonatal, 3 (KCNJ11)
• Allelic: Diabetes mellitus, type 1 (INS)
• Allelic: Diabetes mellitus, type 2 (PAX4)
• Allelic: Diabetes mellitus, type 2, susceptibility to (KCNJ11, PDX1, NEUROD1)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Allelic: Foveal hypoplasia 1 (PAX6)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hepatic adenoma, somatic (HNF1A)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 1 (ABCC8)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 3 (GCK)
• Allelic: Hyperproinsulinemia (INS)
• Allelic: Hypoglycemia of infancy, leucine-sensitive (ABCC8)
• Allelic: Keratitis (PAX6)
• Allelic: Lipodystrophy, familial partial, type 3 (PPARG)
• Allelic: Malouf syndrome (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Morning glory disc anomaly (PAX6)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Obesity, resistance to (PPARG)
• Allelic: Obesity, severe (PPARG)
• Allelic: Optic nerve hypoplasia (PAX6)
• Allelic: Pancreatic agenesis 1 (PDX1)
• Allelic: Pancreatic agenesis and congenital heart defects (GATA6)
• Allelic: Persistent truncus arteriosus (GATA6)
• Allelic: Renal cell carcinoma (HNF1A, HNF1B)
• Allelic: Renal cysts and diabetes syndrome (HNF1B)
• Allelic: Restrictive dermopathy 2 (LMNA)
• Allelic: Testicular anomalies +/- congenital heart disease (GATA4)
• Allelic: Tetralogy of Fallot (GATA4)
• Allelic: Tetralogy of Fallot (GATA6)
• Diabetes Mellitus, noninsulin-dependent, with acanthosis nigricans + hypertension (PPARG)
• Diabetes [panelapp] (PAX6)
• Diabetes mellitus [MONDO:0005015, panelapp] (ZBTB20)
• Diabetes mellitus, insulin-resistant, with acanthosis nigricans (INSR)
• Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Diabetes, type 2 (PPARG)
• Donohue syndrome (INSR)
• Fanconi renotubular syndrome 4, with MODY (HNF4A)
• Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Hutchinson-Gilford progeria (LMNA)
• Hyperinsulinemic hypoglycemia, familial, 5 (INSR)
• Hyperphenylalaninemia, BH4-deficient, D (PCBD1)
• Insulin resistance, severe, digenic (PPARG)
• Lipodystrophy, familial partial, type 2 (LMNA)
• Lipodystrophy, familial partial, type 4 (PLIN1)
• MODY, type I (HNF4A)
• MODY, type II (GCK)
• MODY, type III (HNF1A)
• MODY, type IV (PDX1)
• MODY, type IX (PAX4)
• MODY, type VI (NEUROD1)
• MODY, type VII (KLF11)
• MODY, type VIII (CEL)
• MODY, type X (INS)
• MODY, type XI (BLK)
• MODY, type XIII (KCNJ11)
• MODY, type XIV (APPL1)
• Mandibular hypoplasia, deafness, progeroid features + lipodystrophy syndrome (POLD1)
• Microcephaly, short stature, and impaired glucose metabolism 1 (TRMT10A)
• Mitchell-Riley s.: neonat. diab., pancreatic hypopl., intest. atresia, gallbladder a-/hypopl. (RFX6)
• Neonatal diabetes mellitus [MONDO:0016391, panelapp] (GATA6)
• Pancreatic agenesis and congenital heart defects (GATA6)
• Pancreatic hypoplasia-diabetes-congenital heart disease syndrome [MONDO:0010802, panelapp] (GATA4)
• Permanent neonatal diabetes melllitus [MONDO:0100164, panelapp] (GATA4)
• Pigmented hypertrichotic dermatosis with insulin-dependent diabetes, PHID syndrome (SLC29A3)
• Primrose syndr.: special face, macroceph., ID, calcified ears, sparse hair, muscle wasting (ZBTB20)
• Rabson-Mendenhall syndrome (INSR)
• Transient neonatal diabetes mellitus [MONDO:0020525, panelapp] (GATA4)
• Wolfram syndrome 1 (WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)