Background: The insulin-like growth factor 1 receptor (IGF IR) gene is located on chromosome 15q26.3. Heterozygous 15q26 deletions involving the IGFIR gene are rare, resulting in intrauterine and postnatal growth retardation, developmental delay and microcephaly. Limited evidence exists on the effect of growth hormone (GH) therapy in these cases. Methods: We report a series of cases with 15q26 deletions, including response to GH treatment. Results: Seven children (2 males) presented with short stature [median height standard deviation score (SDS) of -4.8 (range -3.0 to -5.6)]. GH was started at a median age of 5 years (range 1.8 to 12.4) for a median duration of 5.8 years (range 1.0 to 12.4). Median height SDS increased by +0.6 (range 0.1 to 1.0), +1.3 (range 0.1 to 2.4) and +1.4 (range 0.8 to 3.3) after 1 (n = 7), 5 (n = 4) and 10 years (n = 3) of GH treatment, respectively. Four patients reached final height after 5.8 to 12.4 years of GH with a median change in height SDS of +1.1 (range 0 to 3.3). Conclusion: This study demonstrates a moderate, though variable, response to GH therapy, suggesting that GH resistance caused by heterozygous IGFIR deletions can be partially overcome by GH therapy. The first-year response was moderate, and whilst long-term treatment improved height SDS, the final adult height remained reduced. Therefore, an individual trial of GH therapy may be appropriate in these patients.

Walenkamp MJ, Wit JM: Single gene mutations causing SGA. Best Pract Res Clin Endocrinol Metab 2008;22:433-446.
Abbott AM, Bueno R, Pedrini MT, Murray JM, Smith RJ: Insulin-like growth factor I receptor gene structure. J Biol Chem 1992;267:10759-10763.
Davidsson J, Collin A, Bjorkhem G, Soller M: Array based characterization of a terminal deletion involving chromosome subband 15q26.2: an emerging syndrome associated with growth retardation, cardiac defects and developmental delay. BMC Med Genet 2008;9:2.
Nuutinen M, Kouvalainen K, Knip M: Good growth response to growth hormone treatment in the ring chromosome 15 syndrome. J Med Genet 1995;32:486-487.
Okubo Y, Siddle K, Firth H, O'Rahilly S, Wilson LC, Willatt L, Fukushima T, Takahashi S, Petry CJ, Saukkonen T, et al: Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF-IR) gene and a tall child with three copies of the IGF-IR gene. J Clin Endocrinol Metab 2003;88:5981-5988.
Walenkamp MJ, de Muinck Keizer-Schrama SM, de Mos M, Kalf ME, van Duyvenvoorde HA, Boot AM, Kant SG, White SJ, Losekoot M, Den Dunnen JT, et al: Successful long-term growth hormone therapy in a girl with haploinsufficiency of the insulin-like growth factor-I receptor due to a terminal 15q26.2->qter deletion detected by multiplex ligation probe amplification. J Clin Endocrinol Metab 2008;93:2421-2425.
Ester WA, van Duyvenvoorde HA, de Wit CC, Broekman AJ, Ruivenkamp CAL, Lutgarde, LC Govaerts, Wit JM, Hokken-Koelega AC, Losekoot M: Two short children born small for gestational age with insulin-like growth factor 1 receptor haploinsufficiency illustrate the heterogeneity of its phenotype. J Clin Endocrinol Metab 2009;94:4717-4727.
Blum WF, Cotterill AM, Postel-Vinay MC, Ranke MB, Savage MO, Wilton P: Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls. Pharmacia Study Group on insulin-like growth factor I treatment in growth hormone insensitivity syndromes. Acta Paediatrica Supplement 1994;399:117-124.
Woods KA, Camacho-Hubner C, Savage MO, Clark AJ: Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 1996;335:1363-1367.
Wilson GN, Sauder SE, Bush M, Beitins IZ: Phenotypic delineation of ring chromosome 15 and Russel-Silver syndromes. J Med Genet 1985;22:233-236.
Roback EW, Barakat AJ, Dev VG, Mbikay M, Chretien M, Butler MG: An infant with deletion of the distal long arm of chromosome 15 (q26.1-qter) and loss of insulin-like growth factor 1 receptor gene. Am J Med Genet 1991;38:74-79.
Siebler T, Lopaczynski W, Terry CL, Casella SJ, Munson P, De Leon DD, Phang L, Blakemore KJ, McEvoy RC, Kelley RI, et al: Insulin-like growth factor I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15. J Clin Endocrinol Metab 1995;80:3447-3457.
Tonnies H, Schulze I, Hennies H, Neumann LM, Keitzer R, Neitzel H: De novo terminal deletion of chromosome 15q26.1 characterised by comparative genomic hybridisation and FISH with locus specific probes. J Med Genet 2001;38:617-621.
Biggio JR, Descartes MD, Carroll AJ, Holt RL: Congenital diaphragmatic hernia: is 15q26.1-26.2 a candidate locus? Am J Med Genet A 2004;126A:183-185.
Bhakta KY, Marlin SJ, Shen JJ, Fernandes CJ: Terminal deletion of chromosome 15q26.1: case report and brief literature review. J Perinatol 2005;25:429-432.
Pinson L, Perrin A, Plouzennec C, Parent P, Metz C, Collet M, Le Bris MJ, Douet-Guilbert N, Morel F, De Braekeleer M: Detection of an unexpected subtelomeric 15q26.2 -> qter deletion in a little girl: clinical and cytogenetic studies. Am J Med Genet A 2005;138A:160-165.
Rujirabanjerd S, Suwannarat W, Sripo T, Dissaneevate P, Permsirivanich W, Limprasert P: De novo subtelomeric deletion of 15q associated with satellite translocation in a child with developmental delay and severe growth retardation. Am J Med Genet A 2007;143:271-276.
Poot M, Eleveld MJ, van Genderen MM, Verrijin Stuart AA, Hochstenbach R, Beemer FA: Proportional growth failure and oculocutaneous albinism in a girl with a 6.87 Mb deletion of region 15q26.2->qter. Eur J Med Genet 2007;50:432-440.
Rudaks LI, Nicholl JK, Bratkovic D, Barnett CP: Short stature due to 15q26 microdeletion involving IGF1R: report of an additional case and review of the literature. Am J Med Genet A 2011;155:3139-3143.
Dateki S, Fukami M, Tanaka Y, Sasaki G, Moriuchi H, Ogata T: Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis. Endocr J 2011;58:155-159.
Nakamura E, Makita Y, Okamoto T, Nagaya K, Hayashi T, Sugimoto M, Manabe H, Taketazu G, Kajino H, Fujieda K: 5.78 Mb terminal deletion of chromosome 15q in a girl, evaluation of NR2F2 as candidate gene for congenital heart defects. Eur J Med Genet 2011;54:354-356.
Poot M, Stuart A, van Daalen E, van Iperen A, van Binsbergen E, Hochstenbach R: Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases. Eur J Med Gen 2013;56:346-350.
Tillmann V, Buckler JM, Kibirige MS, Price DA, Shalet SM, Wales JK, Addison MG, Gill MS, Whatmore AJ, Clayton PE: Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 1997;82:531-535.
Bakker B, Frane J, Anhalt H, Lippe B, Rosenfeld RG: Height velocity targets from the national cooperative growth study for first-year growth hormone responses in short children. J Clin Endocrinol Metab 2008;93:352-357.
Ranke MB, Lindberg A: Observed and predicted growth responses in prepubertal children with growth disorders: guidance of growth hormone treatment by empirical variables. J Clin Endocrinol Metab 2010:95:1229-1237.
Finkelstein BS, Imperiale TF, Speroff T, Marrero U, Radcliffe DJ, Cuttler L: Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis. Arch Pediatr Adolesc Med 2002;156:230-240.
Bang P, Bjerknes R, Dahlgren J, Dunkel L, Gustafsson J, Juul A, Kristrom B, Tapanainen P, Aberg V: A comparison of different definitions of growth response in short prepubertal children treated with growth hormone. Horm Res Paediatr 2011;75:335-345.
van der Eerden BC, Karperien M, Wit JM: Systemic and local regulation of the growth plate. Endocr Rev 2003;24:782-801.
de Lacerda L, Carvalho JA, Stannard B, Werner H, Boguszewski MC, Sandrini R, Malozowski SN, Leroith D, Underwood LE: In vitro and in vivo responses to short-term recombinant human insulin-like growth factor-1 (IGF-I) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene. Clin Endocrinol (Oxf) 1999;51:541-550.
Tanner JM, Buckler JM: Revision and update of Tanner-Whitehouse clinical longitudinal charts for height and weight. Eur J Pediatr 1997;156:248-249.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.