Temple Syndrome: Comprehensive Clinical Study in Genetically Confirmed 60 Japanese Patients.

Objective: Temple syndrome (TS14) is a rare 14q32.2-related imprinting disorder. Here, we report comprehensive clinical findings in TS14.

Methods: We obtained detailed clinical findings in 60 Japanese patients with genetically confirmed TS14, using a questionnaire to attending physicians. The 60 patients consisted of 31 with UPD(14)mat, 22 with epimutation, five with deletions, and two with UPD(14)mat or epimutation.

Results: Small for gestational age, postnatal (∼2 years of age) short stature, and central precocious puberty (CPP) were identified in 88.3%, 87.0%, and 86.0% of patients, respectively. Growth hormone therapy was performed in 32 patients, increasing the median height SDS for height from -3.4 to -2.4, and gonadotropin-releasing hormone analog therapy was performed in 32 patients, ameliorating CPP. Furthermore, the survey showed intellectual and developmental disabilities in 21.6% of patients, neurodevelopmental disorders in 21.6% of patients, obesity in 20.0% of patients, hypercholesterolemia in 26.5% of patients aged ≥6 years, diabetes mellitus in 12.8% of patients aged ≥9 years, and Silver-Russell syndrome-like and/or Prader-Will syndrome-like phenotypes in 87.7% of patients in infancy. Notably, 42.9% of patients were enrolled in special classes in childhood, whereas 98.2% of patients attended college or had jobs in adulthood. Hypercholesterolemia and diabetes mellitus were observed before the development of obesity in a substantial fraction of TS14 patients, and were controlled by oral medications in most affected patients.

Conclusion: These results clarify the detailed clinical characteristics in TS14. On the basis of the above findings, we propose efficient diagnostic approach and pertinent clinical management for TS14 patients.