Background/Aims: Temple syndrome is an imprinting disorder caused by maternal uniparental disomy of chromosome 14 (mat UPD14), paternal deletion of 14q32 or paternal hypomethylation of the intergenic differentially methylated region (MEG3/DLK1 IG-DMR). Patients with Temple syndrome have pre- and postnatal growth restriction, short stature, hypotonia, small hands and feet and precocious puberty. We sought to determine whether treatment with growth hormone improves growth outcomes in patients with Temple syndrome. Methods: This was a retrospective observational study reviewing the medical records of 14 patients with Temple syndrome, 7 of whom were treated with growth hormone. Results: After 1 year of growth hormone treatment, the height standard deviation score (SDS) increased a median of 1.31 SDS with a median increased height velocity of 5.30 cm/year. Conclusions: These results suggest short-term improvement in height SDS with growth hormone treatment similar to the response in patients treated under the small for gestational age indication. We recommend considering growth hormone therapy in all patients with Temple syndrome who have short stature.

1.
Temple
IK
,
Cockwell
A
,
Hassold
T
,
Pettay
D
,
Jacobs
P
.
Maternal uniparental disomy for chromosome 14
.
J Med Genet
.
1991
Aug
;
28
(
8
):
511
4
.
[PubMed]
0022-2593
2.
Ioannides
Y
,
Lokulo-Sodipe
K
,
Mackay
DJ
,
Davies
JH
,
Temple
IK
.
Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases
.
J Med Genet
.
2014
Aug
;
51
(
8
):
495
501
.
[PubMed]
0022-2593
3.
Briggs
TA
,
Lokulo-Sodipe
K
,
Chandler
KE
,
Mackay
DJ
,
Temple
IK
.
Temple syndrome as a result of isolated hypomethylation of the 14q32 imprinted DLK1/MEG3 region
.
Am J Med Genet A
.
2016
Jan
;
170A
(
1
):
170
5
.
[PubMed]
1552-4825
4.
Hoffmann
K
,
Heller
R
.
Uniparental disomies 7 and 14
.
Best Pract Res Clin Endocrinol Metab
.
2011
Feb
;
25
(
1
):
77
100
.
[PubMed]
1521-690X
5.
Kagami
M
,
Sekita
Y
,
Nishimura
G
,
Irie
M
,
Kato
F
,
Okada
M
, et al
Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes
.
Nat Genet
.
2008
Feb
;
40
(
2
):
237
42
.
[PubMed]
1061-4036
6.
Kagami
M
,
O’Sullivan
MJ
,
Green
AJ
,
Watabe
Y
,
Arisaka
O
,
Masawa
N
, et al
The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers
.
PLoS Genet
.
2010
Jun
;
6
(
6
):
e1000992
.
[PubMed]
1553-7390
7.
Dauber
A
,
Cunha-Silva
M
,
Macedo
DB
,
Brito
VN
,
Abreu
AP
,
Roberts
SA
, et al
Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty
.
J Clin Endocrinol Metab
.
2017
May
;
102
(
5
):
1557
67
.
[PubMed]
0021-972X
8.
Mitter
D
,
Buiting
K
,
von Eggeling
F
,
Kuechler
A
,
Liehr
T
,
Mau-Holzmann
UA
, et al
Is there a higher incidence of maternal uniparental disomy 14 [upd(14)mat]? Detection of 10 new patients by methylation-specific PCR
.
Am J Med Genet A
.
2006
Oct
;
140
(
19
):
2039
49
.
[PubMed]
1552-4825
9.
Hosoki
K
,
Kagami
M
,
Tanaka
T
,
Kubota
M
,
Kurosawa
K
,
Kato
M
,
Uetake
K
,
Tohyama
J
,
Ogata
T
,
Saitoh
S
:
Maternal uniparental disomy 14 syndrome demonstrates prader-willi syndrome-like phenotype.
The Journal of pediatrics
2009
;155:900-903 e901.
10.
Goto
M
,
Kagami
M
,
Nishimura
G
,
Yamagata
T
.
A patient with Temple syndrome satisfying the clinical diagnostic criteria of Silver-Russell syndrome
.
Am J Med Genet A
.
2016
Sep
;
170
(
9
):
2483
5
.
[PubMed]
1552-4825
11.
Kagami
M
,
Mizuno
S
,
Matsubara
K
,
Nakabayashi
K
,
Sano
S
,
Fuke
T
, et al
Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver-Russell Syndrome-compatible phenotype
.
Eur J Hum Genet
.
2015
Aug
;
23
(
8
):
1062
7
.
[PubMed]
1018-4813
12.
Kagami
M
,
Nagasaki
K
,
Kosaki
R
,
Horikawa
R
,
Naiki
Y
,
Saitoh
S
,
Tajima
T
,
Yorifuji
T
,
Numakura
C
,
Mizuno
S
,
Nakamura
A
,
Matsubara
K
,
Fukami
M
,
Ogata
T
: Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients. Genetics in medicine : official journal of the American College of Medical Genetics
2017
13.
Geoffron
S
,
Abi Habib
W
,
Chantot-Bastaraud
S
,
Dubern
B
,
Steunou
V
,
Azzi
S
, et al
Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome
.
J Clin Endocrinol Metab
.
2018
Jul
;
103
(
7
):
2436
46
.
[PubMed]
0021-972X
14.
Guaraldi
F
,
Beccuti
G
,
Gori
D
,
Ghizzoni
L
.
MANAGEMENT OF ENDOCRINE DISEASE: long-term outcomes of the treatment of central precocious puberty
.
Eur J Endocrinol
.
2016
Mar
;
174
(
3
):
R79
87
.
[PubMed]
0804-4643
15.
Glab
E
,
Wikiera
B
,
Bieniasz
J
,
Barg
E
:
The Influence of GnRH Analog Therapy on Growth in Central Precocious Puberty.
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
2016
;25:27-32.
16.
Takahashi
I
,
Takahashi
T
,
Utsunomiya
M
,
Takada
G
,
Koizumi
A
.
Long-acting gonadotropin-releasing hormone analogue treatment for central precocious puberty in maternal uniparental disomy chromosome 14
.
Tohoku J Exp Med
.
2005
Dec
;
207
(
4
):
333
8
.
[PubMed]
0040-8727
17.
Rekers-Mombarg
LT
,
Kamp
GA
,
Massa
GG
,
Wit
JM
;
Dutch Growth Hormone Working Group
.
Influence of growth hormone treatment on pubertal timing and pubertal growth in children with idiopathic short stature
.
J Pediatr Endocrinol Metab
.
1999
Sep-Oct
;
12
(
5
):
611
22
.
[PubMed]
0334-018X
18.
Wakeling
EL
,
Brioude
F
,
Lokulo-Sodipe
O
,
O’Connell
SM
,
Salem
J
,
Bliek
J
, et al
Diagnosis and management of Silver-Russell syndrome: first international consensus statement
.
Nat Rev Endocrinol
.
2017
Feb
;
13
(
2
):
105
24
.
[PubMed]
1759-5029
19.
Stalman
SE
,
Kamp
GA
,
Hendriks
YM
,
Hennekam
RC
,
Rotteveel
J
.
Positive effect of growth hormone treatment in maternal uniparental disomy chromosome 14
.
Clin Endocrinol (Oxf)
.
2015
Nov
;
83
(
5
):
671
6
.
[PubMed]
0300-0664
20.
Tohyama
J
,
Yamamoto
T
,
Hosoki
K
,
Nagasaki
K
,
Akasaka
N
,
Ohashi
T
, et al
West syndrome associated with mosaic duplication of FOXG1 in a patient with maternal uniparental disomy of chromosome 14
.
Am J Med Genet A
.
2011
Oct
;
155A
(
10
):
2584
8
.
[PubMed]
1552-4825
21.
Clayton
PE
,
Cianfarani
S
,
Czernichow
P
,
Johannsson
G
,
Rapaport
R
,
Rogol
A
.
Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society
.
J Clin Endocrinol Metab
.
2007
Mar
;
92
(
3
):
804
10
.
[PubMed]
0021-972X
22.
Smeets
CC
,
Zandwijken
GR
,
Renes
JS
,
Hokken-Koelega
AC
.
Long-Term Results of GH Treatment in Silver-Russell Syndrome (SRS): Do They Benefit the Same as Non-SRS Short-SGA?
J Clin Endocrinol Metab
.
2016
May
;
101
(
5
):
2105
12
.
[PubMed]
0021-972X
23.
de Zegher
F
,
Hokken-Koelega
A
.
Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term
.
Pediatrics
.
2005
Apr
;
115
(
4
):
e458
62
.
[PubMed]
0031-4005
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.