Temple Syndrome: Clinical Findings, Body Composition and Cognition in 15 Patients

Abstract

Background: Temple syndrome (TS14) is an imprinting disorder caused by a maternal uniparental disomy of chromosome 14 (UPD(14)mat), paternal deletion of 14q32 or an isolated methylation defect of the MEG3-DMR. Studies on phenotypical characteristics in TS14 are scarce and patients with TS14 often experience delay in diagnosis, which has adverse effects on their health. TS14 is often characterized as either Prader–Willi-like, Silver–Russell-like or as a Silver–Russell spectrum disorder. Methods: This study describes 15 patients with TS14 who visited the Dutch Reference Center for Prader–Willi-like from December 2018 to January 2022. Results: Eight patients had UPD(14)mat and seven a methylation defect. The most common symptoms were intra-uterine growth retardation (IUGR) (100%), hypotonia (100%), precocious puberty (89%), small for gestational age (SGA) birth (67%), tube feeding after birth (53%) and psycho-behavioral problems (53%). Median (interquartile range (IQR)) IQ was 91.5 (84.25; 100.0), whilst many patients were enrolled in special education (54%). The median (IQR) fat mass % (FM%) SDS was 2.53 (2.26; 2.90) and lean body mass (LBM) SDS −2.03 (−3.22; −1.28). There were no significant differences in clinical characteristics between patients with a UPD(14)mat and a methylation defect. Conclusions: Our patients share a distinct phenotype consisting of IUGR, SGA birth, precocious puberty, hypotonia, tube feeding after birth, psycho-behavioral problems and abnormal body composition with a high FM% and low LBM. Whilst similarities with Prader–Willi syndrome (PWS) and Silver–Russell syndrome (SRS) exist, TS14 is a discernible syndrome, deserving a tailored clinical approach. Testing for TS14 should be considered in patients with a PWS or SRS phenotype in infancy if PWS/SRS testing is negative.

The Effects of 5 Years of Growth Hormone Treatment on Growth and Body Composition in Patients with Temple Syndrome

“…Our group started GH at a median (IQR) age of 7.3 (5.0; 8.4) years, which is relatively late. This is mostly due to the fact that patients with TS14 often experience a delay in diagnosis [5] and GH treatment is not always immediately started. More research is needed to determine whether an earlier start of GH treatment in patients with TS14 leads to better outcomes, as it does in patients with PWS.…”

“…This study describes 13 children (entire group) and a subgroup of 5 prepubertal children (prepubertal group) with a molecular genetic diagnosis of TS14 who visited our Dutch Reference Center for PWS/PWL between December 2018 and May 2022. A detailed description of the patients’ phenotypical traits was reported in a previous publication [5]. Six patients started GH treatment during this period as participants of a GH trial in children with PWL and completed at least 1 year of treatment; 5 out of these 6 patients remained prepubertal.…”

“…Most, but not all, patients have short stature [4]. Almost all patients have central precocious puberty, which is often treated with GnRH analogs (GnRHa) [4][5][6]. Without treatment, central precocious puberty can result in a short adult height.…”

“…Improving body composition is the main reason for GH treatment in patients with PWS. As patients with TS14 have a similar body composition to patients with PWS, with a low lean body mass (LBM) and a high fat mass percentage (FM%) [5], optimizing body composition could be an important reason for GH treatment in this group of patients. As many patients with TS14 do have short stature [4], their growth could also benefit from treatment with GH.…”

Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes

“…For instance, a 4-year-old patient with hetero- and isoUPD14 from mothers on chromosome 14q11.2q24.3 (14q11.2q24.3 (20520197–76786044) x2 hmz) exhibited low birth weight, hypotonia, motor retardation, feeding problems and short stature ( Shin et al, 2016 ). In addition, only a few patients with TS demonstrated obesity, type 2 diabetes mellitus, inguinal hernia, constipation, hyperparathyroidism ( Chan et al, 2019 ) and cognitive development from normal to moderately delayed ( Juriaans et al, 2022 ). So far, TS demonstrated a milder condition, and there is no reported case the same as ours that results in such a rapid death of severe respiratory failure and shock.…”