Bone Status in a Patient with Insulin-Like Growth Factor-1 Receptor Deletion Syndrome: Bone Quality and Structure Evaluation Using Dual-Energy X-Ray Absorptiometry, Peripheral Quantitative Computed Tomography, and Quantitative Ultrasonography

摘要

Haploinsufficiency of the insulin-like growth factor ( IGF )-1 receptor ( IGF1R ) gene is a rare, probably under-diagnosed, cause of short stature. However, the effects of IGF1R haploinsufficiency on glucose metabolism, bone status, and metabolism have rarely been investigated. We report the case of a patient referred to our center at the age of 18?months for short stature, failure to thrive, and Silver–Russell-like phenotype. Genetic analysis did not show hypomethylation of the 11p15.5 region or uniparental disomy of chromosome 7. Growth hormone (GH) stimulation tests revealed GH deficiency, whereas IGF-1 was 248?ng/mL. r-hGH treatment showed only a slight improvement (from ?4.4 to ?3.5 SDS). At 10?years of age, the child was re-evaluated: CGH-array identified a heterozygous de novo 4.92?Mb deletion in 15q26.2, including the IGF1R gene. Dual-energy X-ray absorptiometry showed a normal bone mineral density z -score, while peripheral quantitative computed tomography revealed reduced cortical and increased trabecular elements. A phalangeal bone quantitative ultrasonography showed significantly reduced amplitude-dependent speed of sound and bone transmission time values. The changes in bone architecture, quality, and metabolism in heterozygous IGF1R deletion patients, support the hypothesis that IGF-1 can be a key factor in bone modeling and accrual.