To date, 6 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability is the core feature, together with minor facial dysmorphisms and obesity. We describe the first case of a young patient with a maternally inherited microduplication in 17p13.1 presenting with growth hormone deficiency. The boy was addressed to the endocrine division for growth retardation (weight and height <3rd percentile). Besides minor facial dysmorphisms, physical and neurological examinations were normal except for motor dyspraxia. Basic blood tests and endocrinological investigations were normal, but IGF1 levels were low for his age. Growth hormone deficiency was confirmed. Hypothalamic pituitary MRI was normal. His karyotype was 46XY. Array-CGH analysis detected a 422-kb copy number gain in the spanning region 17p13.1 inherited from his mother. Although familial short stature is considered a “normal” variation of growth retardation, hormonal and genetic investigation is essential in the etiological diagnosis.

Keywords:
Comparative genomic analysis, Familial short stature, Growth hormone deficiency, Microduplication syndrome 17p13.1
1.
Belligni EF, Di Gregorio E, Biamino E, Calcia A, Molinatto C, et al: 790 Kb microduplication in chromosome band 17p13.1 associated with intellectual disability, afebrile seizures, dysmorphic features, diabetes, and hypothyroidism. Eur J Med Genet 55:222-224 (2012).
2.
Blassnig-Ezeh A, Bandelier C, Frühmesser A, Revencu N, Krabichler B, et al: Severe growth retardation, delayed bone age, and facial dysmorphism in two patients with microduplications in 2p16→p22. Am J Med Genet 161:3176-3181 (2013).
3.
Carvalho CM, Vasanth S, Shinawi M, Russell C, Ramocki MB, et al: Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes. Am J Hum Genet 95:565-578 (2014).
4.
Coutton C, Devillard F, Vieville G, Amblard F, Lopez G, et al: 17p13.1 microduplication in a boy with Silver-Russell syndrome features and intellectual disability. Am J Med Genet A 158A:2564-2570 (2012).
5.
Dauber A, Yu Y, Turchin MC, Chiang CW, Meng YA, et al: Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions. Am J Hum Genet 89:751-759 (2011).
6.
Franco LM, de Ravel T, Graham BH, Frenkel SM, Van Driessche J, et al: A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion. Eur J Hum Genet 18:258-261 (2010).
7.
Komoike Y, Shimojima K, Liang JS, Fujii H, Maegaki Y, et al: A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish. J Hum Genet 55:155-162 (2010).
8.
Kuroda Y, Ohashi I, Tominaga M, Saito T, Nagai J, et al: De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity. Am J Med Genet A 164:1550-1554 (2014).
9.
Lukusa T, Fryns JP: Pure de novo 17q25.3 micro duplication characterized by micro array CGH in a dysmorphic infant with growth retardation, developmental delay and distal arthrogryposis. Genet Couns 21:25-34 (2010).
10.
Maini I, Ivanovski I, Iodice A, Rosato S, Pollazzon M, et al: Endocrinological abnormalities are a main feature of 17p13.1 microduplication syndrome: a new case and literature review. Mol Syndromol 7:337-343 (2016).
11.
Mooneyham KA, Holden KR, Cathey S, Dwivedi A, Dupont BR, Lyons MJ: Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome. Am J Med Genet A 164:2887-2891 (2014).
12.
Mul D, Wu S, de Paus RA, Oostdijk W, Lankester AC, et al: A mosaic de novo duplication of 17q21-25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NFkB activation. Eur J Endocrinol 166:743-752 (2012).
13.
Murray PG, Dattani MT, Clayton PE: Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child 101:96-100 (2016).
14.
Roos L, Jønch AE, Kjaergaard S, Taudorf K, Simonsen H, et al: A new microduplication syndrome encompassing the region of the Miller-Dieker (17p13 deletion) syndrome. J Med Genet 46:703-710 (2009).
15.
Thiel CT, Dörr HG, Trautmann U, Hoyer J, Hofmann K, et al: A de novo 7.6 Mb tandem duplication of 14q32.2-qter associated with primordial short stature with neurosecretory growth hormone dysfunction, distinct facial anomalies and mild developmental delay. Eur J Med Genet 51:362-367 (2008).
16.
Wit JM, Oostdijk W, Losekoot M, van Duyvenvoorde HA, Ruivenkamp CA, Kant SG: Mechanisms in endocrinology: novel genetic causes of short stature. Eur J Endocrinol 174:R145-173 (2016).
© 2018 S. Karger AG, Basel
2018
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.