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. 2017 Dec;19(12):1356-1366.
doi: 10.1038/gim.2017.53. Epub 2017 May 31.

Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients

Masayo Kagami  1 , Keisuke Nagasaki  2 , Rika Kosaki  3 , Reiko Horikawa  4 , Yasuhiro Naiki  4 , Shinji Saitoh  5 , Toshihiro Tajima  6 , Tohru Yorifuji  7 , Chikahiko Numakura  8 , Seiji Mizuno  9 , Akie Nakamura  1 , Keiko Matsubara  1 , Maki Fukami  1 , Tsutomu Ogata  1   10
Affiliations

Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients

Masayo Kagami et al. Genet Med. 2017 Dec.

Abstract

PurposeTemple syndrome (TS14) is a rare imprinting disorder caused by aberrations at the 14q32.2 imprinted region. Here, we report comprehensive molecular and clinical findings in 32 Japanese patients with TS14.MethodsWe performed molecular studies for TS14 in 356 patients with variable phenotypes, and clinical studies in all TS14 patients, including 13 previously reported.ResultsWe identified 19 new patients with TS14, and the total of 32 patients was made up of 23 patients with maternal uniparental disomy (UPD(14)mat), six patients with epimutations, and three patients with microdeletions. Clinical studies revealed both Prader-Willi syndrome (PWS)-like marked hypotonia and Silver-Russell syndrome (SRS)-like phenotype in 50% of patients, PWS-like hypotonia alone in 20% of patients, SRS-like phenotype alone in 20% of patients, and nonsyndromic growth failure in the remaining 10% of patients in infancy, and gonadotropin-dependent precocious puberty in 76% of patients who were pubescent or older.ConclusionThese results suggest that TS14 is not only a genetically diagnosed entity but also a clinically recognizable disorder. Genetic testing for TS14 should be considered in patients with growth failure plus both PWS-like hypotonia and SRS-like phenotypes in infancy, and/or precocious puberty, as well as a familial history of Kagami-Ogata syndrome due to maternal microdeletion at 14q32.2.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Photographs of nine patients with Temple syndrome. Silver-Russell syndrome–like craniofacial appearance became less remarkable with age, and truncal obesity became apparent with age.
Figure 2
Figure 2
Growth charts for 15 patients with Temple syndrome. B, breast; G, genitalia; GH, growth hormone; GHD, GH deficiency; GnRHa, gonadotropin-releasing hormone analog; PH, pubic hair; SGA–SS, small for gestational age and short in stature; TH, target height. The vertical bars adjacent to TH indicate target range.
Figure 3
Figure 3
Genotype–phenotype correlations in 16 patients with microdeletions involving the chromosome 14q32.2 imprinted region. The microdeletions were confirmed to be present on the paternally inherited chromosome 14 in patient 30–case 10 (indicated with black left–right double arrows), and are predicted to reside on the paternally inherited chromosome 14 in cases 11–13 on the basis of the phenotype (indicated with gray left–right double arrows). DLK1 and RTL1 shown in blue are PEGs, and the remaining genes shown in black are nonimprinted genes (DIO3 is unlikely to be a PEG). MEGs are shown in gray because they are not expressed from the paternally transmitted chromosome 14. The smallest overlapping region in patients with the TS14 phenotype is shaded with a yellow rectangle that contains DLK1 as the sole gene, and for patients with ID it is shaded with a pink rectangle. ID, intellectual disability; PP, precocious puberty; PWS, Prader-Willi syndrome; SRS, Silver-Russell syndrome; SS, short stature. For sources, see Supplementary Reference S2.
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