ESPE Abstracts (2015) 84 P-2-397

Silver Russell syndrome: A Cause of Partial IGF1 Resistance?

Marie-Noëlle Dufourga, Laurence Perina, Muriel Houanga, Marie-Laure Daubarda, Frédéric Brioudea,b, Yves Le Bouca,b & Irène Netchinea,b


aAP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, F-75012 Paris, France; bSorbonne Universités, UPMC University Paris 06, F-75005 Paris, France


Background: Silver-Russell syndrome (SRS) is characterized by intrauterine and postnatal growth retardation, relative macrocephaly at birth, prominent forehead, severe feeding difficulties and body asymmetry. In around 50%, it is secondary to hypomethylation at the IGF2/H19 imprinted locus on 11p15 (11p15 LOM), and in 10% to a maternal disomy of chromosome 7 (mUPD7). Mechanisms of postnatal growth failure in SRS are not well understood.

Objective and hypotheses: Document IGF1 and IGFBP3 serum levels in SRS without and with GH therapy.

Method: IGF1 and IGFBP-3 serum levels were measured by IRMA and RIA respectively in SRS children without (n=45) and after one year of GH treatment (n=22).

Results: In the 45 children (median age: 3.9 years, median height: −3 SDS, 39 patients with 11p15 LOM and six patients with mUPD7) no IGF1 <−2 SDS level was documented, despite severe feeding difficulties. Basal levels of IGF1 and IGFBP-3 were increased >+2 SDS in respectively 24 and 11% of the SRS children before GH treatment and in 64 and 54% after 1 year of GH, only in the SRS group of patients with 11p15 LOM. The median 1 year growth response to GH (median dose 31 μg/kg per day), expressed as the change in height SDS score, was +0.8 (range 0 to +1.4).

Conclusion: Basal levels of both IGF1 and IGFBP-3 are increased for some SRS with 11p15 LOM even before GH treatment and very frequently during GH treatment. IGF1 levels are more often elevated than IGFBP-3 levels. During the first year of GH, growth velocity increased but only modestly, however GH augmentation was limited by elevated IGF1 levels in most patients. This suggests that SRS patients with 11p15 LOM have a partial IGF1 insensitivity of unknown mechanism complicating thereby the management of GH therapy in this group of patients.

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