PO-0069 Terminal Deletion Of Chromosome 15q Resulting In Haploinsufficiency Of The Igf-1 Receptor And Marked Elevation Of Igf-1

Abstract

<h3>Introduction</h3> Ten to fifteen percent of small for gestational age (SGA) infants demonstrate failure of catch-up growth. Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene due to monosomy 15q is an extremely rare cause with 16 cases reported in the literature. We describe the phenotype of such a patient including biochemical findings, auxology and management. <h3>Case</h3> A three-year-old female with global developmental delay and autistic spectrum disorder was evaluated for short stature. Height was 82 cm (-3.7 SDS) and weight was 12.5 kg (-1.3 SDS). She was born at term weighing 2.88 kg and was microcephalic and dysmorphic. Array CGH revealed an unbalanced translocation resulting in trisomy of the terminal portion of chromosome 10p and monosomy 15q26.3- &gt;qter which contains the region coding for IGF1R. IGF-1(243 µg/L) and IGFBP-3 (3501 ng/ml) levels were markedly elevated; +4.7 SDS and +3.3 SDS respectively. The marked elevation in IGF-1 levels was considered a relative contraindication to GH therapy. <h3>Discussion</h3> Haploinsufficency of IGF1R gene is associated with elevated levels of IGF-1 as a result of target organ resistance. Exogenous growth hormone, while further elevating IGF-1, in many cases facilitates catch-up growth albeit to a lesser extent than other ex-SGA infants. In this case IGF-1 levels were exceptionally high, precluding growth hormone therapy. <h3>Conclusion</h3> Deletions involving the IGF1R gene are a rare but treatable cause of short stature. This case is unusual however, as marked elevation of IGF-1 at baseline precluded GH therapy.