Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Infants born small for gestational age (SGA) are susceptible to metabolic complications.
• Insulin-like growth factor 1 (IGF-1) resistance, caused by IGF-1 receptor (IGF1R) mutations, is a rare genetic disorder leading to proportionate growth retardation.
• The link between impaired IGF1R function and comorbidities like disturbed glucose homeostasis is not fully understood.

Observation:

• Genetic analysis of two SGA male siblings and their father identified a novel heterozygous mutation (p.Cys1248Tyr) in the IGF1R gene.
• Both brothers exhibited similar growth patterns, even during recombinant human growth hormone treatment.
• Oral glucose tolerance tests revealed variable progressive impaired glucose tolerance in the brothers, while the father had developed type 2 diabetes mellitus.

Findings:

• The identified novel IGF1R mutation is strongly associated with proportionate growth retardation in the affected siblings.
• The IGF1R mutation appears to predispose individuals to disturbances in carbohydrate homeostasis, as evidenced by impaired glucose tolerance and type 2 diabetes.

Implications:

• This study highlights the potential role of IGF1R mutations in the development of metabolic complications, particularly glucose intolerance, in SGA individuals.
• Close metabolic monitoring is crucial for patients with IGF1R mutations, especially when initiating growth hormone therapy.
• Further research into the mechanisms linking IGF1R function to glucose homeostasis is warranted.