Table 1.

Characteristic clinical features of subjects with Donohue syndrome (DS), Rabson–Mendenhall Syndrome (RMS) and Type A Insulin Resistance (Type A IR) [3,5,6,7,8,10,49,50,56,57,58,59,60,61,62,63].

	DS	RMS	Type A Insulin Resistance
Molecular genetics	Homozygous mutation in the insulin receptor (INSR) gene	Compound heterozygous mutation in INSR gene	Mutation in the insulin receptor gene (autosomal-dominant or autosomal-recessive)
Face	Proptosis	Resembling DS	Normal phenotype
	Infraorbital folds	or milder phenotype
	Large, posteriorly rotated ears
	Thick lips
	Gingival hyperplasia
	Broad nasal tip
Other	Large hands and feet (relative to body) Gingival hypertrophy	Early dentition and dental crowding Nail dysplasia	Usually not obese
	Abdominal distension
	Reduced lateral thoracic dimension
	Hyperplasia of nipples	Hyperplasia of nipples
	Genital enlargement	Genital enlargement
	Intrauterine growth restriction	Growth retardation (less severe than in DS)	Normal growth
	Postnatal failure to thrive
Organ pathologies	Organomegaly (kidney, liver, spleen)	Organomegaly (kidney, liver, spleen)
	Hypertrophic cardiomyopathy (HCOM)	Hypertrophic cardiomyopathy
	Nephrocalcinosis Renal tubular dysfunction	Nephrocalcinosis Renal tubular dysfunction
	Enlarged polycystic ovaries	Enlarged polycystic ovaries	Polycystic ovaries
	Rectal prolapse	Second decade: microvascular complications
	Cholestasis	Retinopathy Peripheral neuropathy Renal vascular complications
Skin Features	Hypertrichosis	Hypertrichosis	Hirsutism
	Acanthosis nigricans	Acanthosis nigricans	Acanthosis nigricans
	Hyperkeratosis
	Thick, hyperelastic skin
	Dry skin
	Decreased subcutaneous fat mass
Biochemical Findings	Hyperinsulinemia	Same as DS in first year	Hyperinsulinemia or
	Extremely elevated plasma insulin and C-peptide levels	of live Insulin level decline steadily	extreme resistance to exogenous insulin
	Hyperglycemia	Resulting in increased	Hyperandrogenism
	Fasting hypoglycemia	glucose levels, fewer hypoglycemic events	Increased serum testosterone
	Absence of ketoacidosis	Risk of ketoacidosis
	Decreased IGF-I and IGFBP-3 serum concentrations Hypercalciuria	Decreased IGF-I levels and IGFBP-3 Low triglyceride levels, high HDL levels Hypercalciuria
Neurological Findings	Severe global developmental delay	Variable developmental	No general impairment
	Axial hypotonia	delay to normal
	Muscle atrophy	Intelligence
Life expectancy	Usually death within first two years of life, due to intercurrent infections, severe hypoglycemia, cardiomyopathy	Usually death within second decade of life, due to ketoacidosis or microvascular complications