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.