Background: We already described a partial IGF1 primary deficiency due to an exon 4 homozygous missense mutation (g.65941 G>A). A few patients are now described with a heterozygous IGF1 deletion or mutation, questioning about IGF1 haplo insufficiency role in short stature.
Results: We describe a boy born from consanguineous parents, with an intra uterine growth restriction (IUGR). Birth weight: 2520 g (−1 SDS) birth length: 46 cm (−2 SDS), and head circumference: 33.5 cm (−1 SDS) at 39 weeks. Mothers height was 147 cm (−2.9 SDS) and fathers height was 173 cm (0 SDS). This child had a history of failure to thrive. At presentation at 2 years, he had post natal growth failure, his height was at 80.5 cm, (−2 SDS) and weight at 8.720 kg (−2 SDS), and a normal head circumference. He had no frontal bossing and no hemi hypotrophy. Penis and testes were normal. Usual nutritional markers and free T4, TSH levels were normal, IGF1 was at 33 ng/ml (n: 13136) in the lower range contrasting with a mildly elevated IGFBP3 at 3 μg/ml (n: 0.953.35). Direct sequencing of IGF1 gene revealed an exon 4 heterozygous mutation g.65941 G>A that we had previously identified in some relatives of this new patient. We had demonstrated that the resulting protein (IGF1-R36Q) had a 4 times lower affinity to the IGF Receptor than the WT. In this new patient, the molecular defect inherited probably from his mother, raises the question of its repercussion on the placenta function and on the foetal growth when present even at a heterozygous status only.
Conclusion: We speculate that IGF1 signaling may act in a dose-dependent way leading to a mild impaired growth phenotype in this case.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology