Clinical Report: Temple Syndrome in 60 Genetically Confirmed Japanese Patients
Overview
This study presents comprehensive clinical data on 60 Japanese patients with genetically confirmed Temple syndrome (TS14), highlighting frequent features such as small for gestational age, postnatal short stature, and central precocious puberty. The report also details the effectiveness of growth hormone and GnRH analog therapies, neurodevelopmental outcomes, and metabolic complications including obesity, hypercholesterolemia, and diabetes mellitus.
Background
Temple syndrome (TS14) is a rare imprinting disorder caused by genetic or epigenetic abnormalities in the 14q32.2 region, including maternal uniparental disomy 14, epimutations, and deletions. Clinically, TS14 is characterized by prenatal and postnatal growth failure, Silver-Russell and Prader-Willi syndrome-like features in infancy, and central precocious puberty in childhood. Additional complications include psychomotor developmental delay, metabolic disturbances, and placental hypoplasia. Despite advances, long-term outcomes and detailed phenotypic features require further elucidation.
Data Highlights
Clinical Feature
Prevalence (%)
Small for gestational age (SGA)
88.3
Postnatal short stature (~2 years)
87.0
Central precocious puberty (CPP)
86.0
Intellectual/developmental disabilities
21.6
Neurodevelopmental disorders
21.6
Obesity
20.0
Hypercholesterolemia (≥6 years)
26.5
Diabetes mellitus (≥9 years)
12.8
Special class enrollment in childhood
42.9
College attendance or employment in adulthood
98.2
Key Findings
88.3% of patients were small for gestational age at birth.
87.0% exhibited postnatal short stature around 2 years of age.
86.0% developed central precocious puberty, effectively managed with GnRH analog therapy.
Growth hormone therapy in 32 patients improved median height SD score from −3.4 to −2.4.
Approximately 21.6% had intellectual and neurodevelopmental disabilities, with 42.9% requiring special education during childhood but 98.2% achieving college attendance or employment in adulthood.
Metabolic complications included obesity (20%), hypercholesterolemia (26.5% in patients aged ≥6 years), and diabetes mellitus (12.8% in patients aged ≥9 years), often preceding obesity and controlled by oral medications.
Clinical Implications
Clinicians should consider TS14 in patients presenting with SGA, postnatal short stature, and CPP, especially when accompanied by SRS- or PWS-like features. Early intervention with growth hormone and GnRH analog therapies can improve growth and pubertal outcomes. Monitoring for neurodevelopmental issues and metabolic complications such as hypercholesterolemia and diabetes mellitus is essential, even before obesity develops, to enable timely management.
Conclusion
This comprehensive analysis clarifies the clinical spectrum and natural history of Temple syndrome, supporting an efficient diagnostic approach and tailored management strategies to improve patient outcomes across growth, development, and metabolic health.
References
Ogata et al. 2023 -- Temple Syndrome: In-Depth Clinical Analysis of 60 Genetically Verified Japanese Patients
