Clinical Scorecard: Temple Syndrome: In-Depth Clinical Analysis of 60 Genetically Verified Japanese Patients
At a Glance
Category
Detail
Condition
Temple syndrome (TS14), a rare 14q32.2-related imprinting disorder
Key Mechanisms
Loss of DLK1 expression causing central precocious puberty and growth/metabolic abnormalities; involvement of RTL1 and epigenetic alterations (UPD(14)mat, epimutation, deletions)
Target Population
Patients with genetically confirmed TS14, including maternal uniparental disomy 14, epimutation, and deletions
Care Setting
Specialized clinical genetics and pediatric endocrinology settings
Key Highlights
High prevalence of small for gestational age (88.3%), postnatal short stature (~2 years, 87.0%), and central precocious puberty (86.0%) in TS14 patients
Metabolic complications include obesity (20.0%), hypercholesterolemia (26.5% in patients ≥6 years), and diabetes mellitus (12.8% in patients ≥9 years), often preceding obesity
Intellectual/developmental disabilities and neurodevelopmental disorders present in ~21.6%; majority attend college or work in adulthood despite childhood special class enrollment
Guideline-Based Recommendations
Diagnosis
Confirm TS14 by identifying (epi)genetic aberrations in chromosome 14q32.2 imprinted region via genetic testing
Consider TS14 diagnosis in patients with SGA, postnatal short stature, SRS-like and/or PWS-like features, and central precocious puberty
Use methylation analysis and genetic testing to differentiate UPD(14)mat, epimutation, and deletions
Management
Administer growth hormone (GH) therapy to improve height SDS in patients with short stature
Use GnRH analog therapy to manage central precocious puberty effectively
Monitor and treat metabolic complications such as hypercholesterolemia and diabetes mellitus with appropriate oral medications
Provide developmental support and educational accommodations as needed
Monitoring & Follow-up
Regular assessment of growth parameters including height, weight, and bone age
Monitor pubertal development and initiate GnRH analog therapy when indicated
Screen for metabolic complications including lipid profile and glucose metabolism starting in early childhood
Evaluate neurodevelopmental status and cognitive function periodically
Risks
Risk of central precocious puberty leading to early maturation
Potential for intellectual and neurodevelopmental disabilities
Metabolic risks including obesity, hypercholesterolemia, and diabetes mellitus even before obesity onset
Patient & Prescribing Data
60 genetically confirmed Japanese TS14 patients including UPD(14)mat, epimutation, and deletion subtypes
GH therapy improved median height SD score from −3.4 to −2.4; GnRH analog therapy effectively ameliorated central precocious puberty; metabolic complications controlled by oral medications in most cases
Clinical Best Practices
Early genetic testing for suspected TS14 based on clinical features and growth patterns
Timely initiation of GH and GnRH analog therapies to optimize growth and pubertal outcomes
Comprehensive metabolic screening and management starting in childhood
Multidisciplinary approach including endocrinology, genetics, developmental pediatrics, and metabolic specialists
Long-term follow-up into adulthood to monitor educational and occupational outcomes
