Intrauterine twin discordancy followed by partial postnatal catch-up growth in a girl with a pathogenic IGF1R mutation

Background: IGF-1 is essential for normal human growth in utero and postnatally. It mediates its effects through the IGF-1 receptor (IGF1R), a widely expressed cell surface tyrosine kinase receptor.

Objective: The aim of the study was to analyze pre- and postnatal growth, clinical features and laboratory findings of discordant twins: one small for gestational age (SGA) girl and one appropriate for gestational age (AGA) brother in whom discordant postnatal growth persisted.

Patient and methods: A girl born with a low weight and length (-2.4 SDS) but borderline low head circumference (-1.6 SD) presented with a height of -1.7 SDS, in contrast to a normal height twin brother (0.0 SDS). Because of elevated serum IGF-1 levels, IGF-1 resistance was suspected.

Results: Sequencing revealed the presence of a previously described pathogenic heterozygous mutation (p.Glu1050Lys) in the SGA girl, not present in the parents nor the AGA twin brother.

Conclusions: The pathogenic IGF1R mutation in this girl led to intrauterine growth retardation followed by partial postnatal catch-up growth. Height in mid-childhood was in the lower half of the reference range, but still 1.7 SD shorter than her twin brother.