Intrauterine Twin Discordancy and Partial Postnatal Catch-up Growth in a Girl with a Pathogenic IGF1R Mutation
Paula Ocaranza1, Monique Losekoot2, Marie J. E. Walenkamp3, Christiaan De Bruin4, Jan M. Wit4, Veronica Mericq11University of Chile Faculty of Medicine, Institute of Maternal and Child Research, Santiago, Chile2Leiden University Medical Center, Department of Clinical Genetics, Leiden, The Netherlands
3Emma Children’s Hospital, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
4Leiden University Medical Center, Department of Pediatrics, Leiden, The Netherlands
Objective: Insulin like growth factors-1 (IGF-1) is essential for normal in utero and postnatal human growth. It mediates its effects through the IGF-1 receptor (IGF1R), a widely expressed cell surface tyrosine kinase receptor. The aim of the study was to analyze pre- and post-natal growth, clinical features and laboratory findings in a small for gestational age (SGA) girl in whom discordant postnatal growth persisted and her appropriate for gestational age (AGA) brother.
Methods: A girl born with a low weight and length [-2.3 and -2.4 standard deviation (SD) score (SDS), respectively] 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). IGF-1 resistance was suspected because of elevated serum IGF-1 levels.
Results: Sequencing revealed the presence of a previously described pathogenic heterozygous mutation (p.Glu1050Lys) in the SGA girl which was not present in the parents nor in the AGA twin brother.
Conclusion: 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.
Manuscript Language: English
