Endocrine Abstracts

Introduction: The IGF1-receptor (IGF1R) gene is located on the distal long arm of chromosome 15 (bands q26.3). Short stature due to mutation or deletion of IGF1R gene is rare. Mutation of this gene is better known compared to deletion as a cause of growth hormone resistance. We report a girl with pre and postnatal growth failure with chromosome 15q deletion and 16q duplication.

Case report: Our patient was born at term weighing 2.7 kg (2nd centile). She was ventilated for 2 days for respiratory distress syndrome. She had multiple VSD, dysmorphic features of flat mid-face, small mouth, thin upper lip and limb deformities of prominent interphalangeal joints and bilateral metatarsus varus. At 6 weeks old she required tracheostomy for congenital subglottic stenosis. Chromosomal analysis showed 15q deletion and unbalanced duplication of 16q [46xx, del(15) t(15;16) (q26.1:q22.3)]. The father was a balanced translocation carrier of chromosome 15 and 16. She had moderate learning difficulties and developmental delay. At age 5, both weight and height were <2 SDS. Bone age was delayed by 2.7 years. IGF1 was 2.5 nmol/l (4–20) and IGFBP3 was normal. GH stimulation test to glucagon was normal. By age 10, her height was −2.6 SDS. Repeat IGF1 was 11.8 nmol/l (12–50). Comparative genomic hybridisation (CGH) studies refined breakpoints to (q26.3:q23.1) and interestingly, the IGF1R gene was not deleted as it was proximal to the deletion. She is awaiting commencement of growth hormone therapy.

Conclusion: Pre and postnatal growth failure due to IGF1-receptor gene deletion on chromosome 15 is rare. These children have dysmorphic features and limb deformities. Although her IGF1R gene was not deleted, she fits the described features and we hypothesise that epigenic effects have lead to functional IGF1-receptor dysfunction. Alternately her low IGF1 represents partial IGF1 deficiency. Previous case report has reported benefit from growth hormone therapy.