Monogenic diabetes: An evidence-based clinical approach

Table 1 Various categories of monogenic diabetes with genes involved in the pathogenesis and the clinical features, with special emphasis on monogenic diabetes other than maturity-onset diabetes of the young and neonatal diabetes mellitus

Types	Subtypes/varieties	Gene/protein	Clinical features	Inheritance
MODY	MODY 1 to 14	See Table 2		See Table 2
Neonatal diabetes	Permanent NDM	See Table 2		See Table 2
	Transient NDM	See Table 2		See Table 2
Other monogenic diabetes with defective insulin synthesis and secretion	Mitochondrial DM	m.3243A > G	Maternally inherited diabetes and deafness	Maternal
	Wolfram syndrome 1 or 2	WFS1 or CISD2	DIDMOAD 1 or 2 diabetes insipidus, diabetes mellitus, optic atrophy and deafness	AR
	Rogers syndrome	SLC19A2	Thiamine-responsive megaloblastic anaemia, deafness, and diabetes	AR
	H or PHID syndrome	SLC29A3	H syndrome: Hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomaly, hearing loss, low height, hypogonadism and hyperglycaemia; PHID syndrome	AR
Monogenic autoimmune diabetes syndromes	IPEX syndrome	FOXP3	IPEX syndrome	XR
		LRBA	Common variable immunodeficiency 8	AR
		STAT3	Infancy-onset multi-system autoimmune disease type 1	AD
	APECED syndrome	AIRE	Autoimmune polyendocrinopathy syndrome type 1	AR
		IL2RA	Immunodeficiency 41 with lymphoproliferation and autoimmunity	AR
	IPEX-like syndrome	STAT1	IPEX-like syndrome	AD
		STAT5B	Growth defect, primary immunodeficiency, and endocrine abnormalities	AR
Insulin resistance syndromes	Congenital generalized lipodystrophy (Seip-Berardinelli syndrome)	AGPAT2	CGL1-acromegalic features	AR
		BSCL2	CGL2-cardiomyopathy, polyneuropathy, mental retardation	AR
		CAV1	CGL3-short stature, pulmonary arterial hypertension, and vitamin D resistance	AR
		PTRF	CGL4-congenital myopathy, pyloric stenosis, cardiomyopathy, atlantoaxial instability	AR
	Partial lipodystrophy	LMNA	FPLD2-fat loss from limbs; fat deposition in face, neck and perineum (Dunnigan variety)	AD
		PPARG	FPLD3-loss of subcutaneous fat from distal extremities	AD
		PLIN1	FPLD4-loss of subcutaneous fat from extremities	AD
		AKT2	AKT2 linked FPLD-loss of subcutaneous fat from extremities	AD
		CIDEC	FPLD5-fat loss of lower limbs and abdomen, and multilocular lipid droplets	AR
		LIPE	FPLD6-upper body pseudo-lipomatosis, fat loss from limbs, and muscle atrophy in some cases	AR
		LMNA	Mandibuloacral dysplasia A syndrome-skeletal anomaly, loss of extremity fat, neuropathy, premature ageing	AR
		ZMPST24	Mandibuloacral dysplasia B syndrome-skeletal anomaly, loss of fat, premature renal failure, progeroid	AR
		PIK3R1	SHORT syndrome	AD
		POLD1	MDPL syndrome	De novo
		WRN	Werner syndrome-progeria and cataract	AR

MODY: Maturity-onset diabetes of the young; DM: Diabetes mellitus; NDM: Neonatal diabetes mellitus; IPEX syndrome: Immuno-dysregulation, polyendocrinopathy, enteropathy, X-linked; PHID: Pigmented hypertrichosis and insulin-dependent diabetes mellitus; APECED: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; DIDMOAD: Diabetes insipidus, diabetes mellitus, optic atrophy and deafness; AD: Autosomal dominant; AR: Autosomal recessive; XR: X-linked recessive; CGL: Congenital generalized lipodystrophy; FPLD: Familial partial lipodystrophy; SHORT: Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly and teething delay; MDPL: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome.