Temple syndrome - an under-recognised multi-system growth disorder: large cohort analysis and proposed scoring system.

CONTEXT: Temple syndrome (TS14) is an imprinting disorder caused by abnormalities at chromosome 14q32.2. Its phenotype overlaps with Silver-Russell (SRS) and Prader-Willi (PWS) syndromes, contributing to under-recognition and delayed diagnosis. Its endocrine manifestations remain incompletely characterised. OBJECTIVE: To report the largest TS14 cohort to date to define the endocrine and clinical phenotype, evaluate management, response to growth hormone (GH) therapy, and develop a novel TS14-specific clinical score. DESIGN: Multicentre cohort study. SETTING: Specialist centres in United Kingdom and The Netherlands. PATIENTS: Seventy-one individuals with TS14. MAIN OUTCOME MEASURE: Endocrine and growth-related phenotypes, metabolic complications, and diagnostic performance of a scoring system. RESULTS: Genetic subtypes included maternal uniparental disomy (52%), hypomethylation (41%) and deletion (6). Most patients were born small for gestational age (68%). 73% had short stature at age 1-3 years, improving to 15% at age 11-14 years, with a greater improvement in those treated with GH. Baseline IGF-1 concentrations were ≥-2 SDS in all patients, while GH deficiency (GHD) was confirmed in 27%. Early feeding difficulties affected 87%, 47% developed obesity, and 20% had hyperphagia. Dyslipidaemia was present in 38% and central precocious puberty in 62%. Only 56.5% fulfilled ≥3 criteria of the Netchine-Harbison scoring system. We present a scoring system to identify which patients should be tested for TS14. CONCLUSION: The endocrine phenotype of TS14 encompasses growth failure, GHD, precocious puberty and disordered appetite, and requires age-specific management. Response to GH therapy was promising. A TS14-specific scoring system could enable earlier diagnosis and endocrine intervention, potentially improving outcomes.