ESPE Abstracts

Background: Recently we described a family with several members having intrauterine and postnatal growth failure as well as signs of Silver–Russell syndrome (SRS) who carried a heterozygote nonsense mutation of IGF2. The patients had low IGF-II serum levels, but normal IGF-I serum levels.

Objective and hypotheses: We aimed to estimate the diagnostic value of the IGF-II, IGF-I and IGFBP-3 measurements in the assessment of children with SRS.

Method: We collected data from 52 genetically analysed children with SRS and 113 children with non-syndromic SGA short stature, seen during the last 20 years in our centre. Patients were prepubertal and GH treatment naive. The SRS patients fulfilled ≥4 of the following criteria: SGA, failure to thrive, short stature, relative macrocephaly, prominent forehead or skeletal asymmetry. 11p15 loss of methylation (11p15LOM) was present in 22 patients, maternal uniparental disomy of chromosome 7 (UPD7mat) in seven patients and IGF2 nonsense mutation (IGF2mut) in three patients. There were two carriers of structural chromosomal aberrations outside of 11p15 and 18 patients were tested negative (idiopathic). The SRS children were 4.7±2.1 years and the 113 SGA children 5.7±1.8 years of age. IGF-II, IGF-I and IGFBP-3 were measured by the same in-house RIAs during the full study period.

Results: The median IGF-II SDS values were in the different diagnostic categories in increasing order: IGF2mut -1.75, UPD7mat -1.69, non-syndromic SGA -1.55, idiopathic -0.65, and 11p15LOM -0.61. The median IGF-II to IGF-I concentration ratio was lowest with 2.57 (range; 2.51–2.96) in IGF2mut contrasting to a ratio of 5.44 (3.01–11.20) in 11p15LOM (P=0.036), 7.35 (3.19–13.82) in idiopathic, and 7.98 (5.31–10.52) in UPD7mat. Patients with UPD7mat had significantly lower values of IGF-I and IGFBP-3 than patients with 11p15LOM (P≤0.002).

Conclusion: The molecular diagnosis in SRS can be predicted based on IGFs and IGFBP-3.