Abstract
Temple syndrome is a rare imprinting disorder, caused by alterations in the critical imprinted region 14q32 of chromosome 14. It is characterized by pre- and postnatal growth retardation, truncal hypotonia and facial dysmorphism in the neonatal period. We report an 18-year-old girl with a late diagnosis of Temple syndrome presenting with all typical signs and symptoms including small for gestational age at birth, feeding difficulties, muscle hypotonia and delayed developmental milestones, central precocious puberty, truncal obesity and reduced growth. The patient is the second reported in the literature with signs of clinical and biochemical hyperandrogenism and the first treated with Dehydrocortisone®, with a good response. The clinical diagnosis of this patient was made after long-term follow up at a single center for rare endocrine diseases, and a molecular genetics diagnosis of complete hypomethylation of 14q32 chromosome imprinting center (DLK/GTL2) was recently established. Growth hormone treatment was not given and although precocious puberty was treated in line with standard protocols, her final height remained below the target range. Increased awareness of Temple syndrome and timely molecular diagnosis enables improvement of clinical care of these patients as well as prevention of inherent metabolic consequences.
Keywords: Temple syndrome, late diagnosis, long-term follow-up
Read the full text
4 sections · 2 figures · 2 tables · PDF
Create your free account to read the full text.
- Full text with figures and tables
- PDF and supplementary files
- Access on every Galenos journal
One Galenos account works on every Galenos journal site.
References
Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P. Maternal uniparental disomy for chromosome 14. J Med Genet. 1991;28:511-514.
Gillessen-Kaesbach G, Albrecht B, Eggermann T, Elbracht M, Mitter D, Morlot S, van Ravenswaaij-Arts CMA, Schulz S, Strobl-Wildemann G, Buiting K, Beygo J. Molecular and clinical studies in 8 patients with Temple syndrome. Clin Genet. 2018;93:1179-1188. Epub 2018 Mar 25
Beygo J, Mertel C, Kaya S, Gillessen-Kaesbach G, Eggermann T, Horsthemke B, Buiting K. The origin of imprinting defects in Temple syndrome and comparison with other imprinting disorders. Epigenetics. 2018;13:822-828.
Temple IK, Shrubb V, Lever M, Bullman H, Mackay DJ. Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14. J Med Genet. 2007;44:637-640. Epub 2007 Jun 29
Buiting K, Kanber D, Martín-Subero JI, Lieb W, Terhal P, Albrecht B, Purmann S, Gross S, Lich C, Siebert R, Horsthemke B, Gillessen-Kaesbach G. Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster. Hum Mutat. 2008;29:1141-1146.
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;170:70-175. Epub 2015 Sep 23
Kagami M, Yanagisawa A, Ota M, Matsuoka K, Nakamura A, Matsubara K, Nakabayashi K, Takada S, Fukami M, Ogata T. Temple syndrome in a patient with variably methylated CpGs at the primary MEG3/DLK1:IG-DMR and severely hypomethylated CpGs at the secondary MEG3:TSS-DMR. Clin Epigenetics. 2019;11:42.
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;51:495-501. Epub 2014 Jun 2
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;83:671-676. Epub 2015 Jul 28
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. Genet Med. 2017;19:1356-1366. Epub 2017 May 31
Luk HM. Temple syndrome misdiagnosed as Silver-Russell syndrome. Clin Dysmorphol. 201;25:82-83.
Hoffmann K, Heller R. Uniparental disomies 7 and 14. Best Pract Res Clin Endocrinol Metab. 2011;25:77-100.
Kimura T, Kagami M, Matsubara K, Yatsuga S, Mukasa R, Yatsuga C, Matsumoto T, Koga Y. Temple syndrome diagnosed in an adult patient with clinical autism spectrum disorder. Clin Case Rep. 2018;7:15-18.
Mackay D, Bliek J, Kagami M, Tenorio-Castano J, Pereda A, Brioude F, Netchine I, Papingi D, de Franco E, Lever M, Sillibourne J, Lombardi P, Gaston V, Tauber M, Diene G, Bieth E, Fernandez L, Nevado J, Tümer Z, Riccio A, Maher ER, Beygo J, Tannorella P, Russo S, de Nanclares GP, Temple IK, Ogata T, Lapunzina P, Eggermann T. First step towards a consensus strategy for multi-locus diagnostic testing of imprinting disorders. Clin Epigenetics. 2022;14:143.
Mitter D, Buiting K, von Eggeling F, Kuechler A, Liehr T, Mau-Holzmann UA, Prott EC, Wieczorek D, Gillessen-Kaesbach G. 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;140:2039-2049.
Lande A, Kroken M, Rabben K, Retterstøl L. Temple syndrome as a differential diagnosis to Prader-Willi syndrome: Identifying three new patients. Am J Med Genet A. 2018;176:175-180. Epub 2017 Nov 21
Azzi S, Salem J, Thibaud N, Chantot-Bastaraud S, Lieber E, Netchine I, Harbison MD. A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome. J Med Genet. 2015;52:446-453. Epub 2015 May 7
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;170:2483-2485. Epub 2016 Jun 30
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. J Pediatr. 2009;155:900-903. Epub 2009 Oct 1
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;92:804-810. Epub 2007 Jan 2
Brightman DS, Lokulo-Sodipe O, Searle BA, Mackay DJG, Davies JH, Temple IK, Dauber A. Growth Hormone Improves Short-Term Growth in Patients with Temple Syndrome. Horm Res Paediatr. 2018;90:407-413. Epub 2019 Mar 5
Nordenström A, Falhammar H. MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency. Eur J Endocrinol. 2019;180:127-145.
Wakeling EL, Brioude F, Lokulo-Sodipe O, O’Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13:105-124. Epub 2016 Sep 2
Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab. 2008;93:4183-4197. Epub 2008 Aug 12 Erratum in: J Clin Endocrinol Metab. 2010;95:5465.
