ESPE Abstracts

Introduction: The first patient with Temple syndrome (TS, ORPHA 254516) was described in 1991. The genetic condition is rare (prevalence<1/1000 000, <100 described patients). An abnormal expression of genes in the imprinted 14q32.2 region has been revealed. The 14.32.2 region is characterized by three differentially methylated regions (DMRs) and a cluster of paternally and maternally expressed genes. Main clinical features are growth delay (pre-and postnatal), feeding difficulties, muscular hypotonia, developmental delay, facial dysmorphia, small hands and feet, central obesity, premature puberty. TS patients could present as Prader-Willi –like or Silver Russel spectrum disorder patients, the diagnosis is often delayed, longitudinal follow up data are scarce.

Material and methods: DNA extraction from peripheral blood, Whole exome sequencing (WES) and MS-MLPA (ME032 UPD7-UPD14) analysis were performed.

Case Presentation: Girl, born after 2^nd pregnancy (adopted), Sectio Caesarea, 40 gw, BW 1300g (SDS -6.08), BL 40 cm (SDS-4.6), HCF 30 cm (SDS -3.5), severe asphyxia; start of rhGH at 2 yrs (SDS_h -3.3 at start, low IGF1, hypoplastic anterior pituitary, partial hypoplasia corpus callosum, BA delay, hypoglycemia, GH<7 ng/ml), facial dysmorphism (broad, prominent forehead, short nose, flat nasal root, wide tip, downturned corners of mouth, micrognathia), acromicria. Linear catch up growth (rhGH dosages 20-30 mcg/kg/d, IGRO prediction model). Developmental delay (speech). Hyperphagia& behavioral problems. At 6.6 yrs: truncal obesity, precocious puberty, abrupt BA advancement (11 yrs), insulin resistance. Start of LH-RH, progression in insulin resistance, linear growth despite low rhGH dosages. Suspicion of TS.

COL9A3 mutations are found in pts with short stature. Variant COL9A3 -c.266G>A, p.Gly89Glu is novel and classified as variant of uncertain significance, its contribution to the clinical phenotype could not be excluded.

Conclusion: SGA/IUGR patients represent etiologically a very heterogeneous group. Differential diagnosis in overlapping PW-SRS phenotypes should include Temple syndrome. Extensive molecular studies (WES, WGS) should become more affordable in the routine work up of short stature.

Acknowledgements: Grant: D01-302/17.12.2021, D01-165/28.07.2022, MES:D-132/14.06.2022