Temple Syndrome

A number sign (#) is used with this entry because Temple syndrome is an imprinting disorder involving genes within the imprinted region of chromosome 14q32.

Description

Temple syndrome is a short stature disorder of imprinting. The cardinal features are low birth weight, hypotonia and motor delay, feeding problems early in life, early puberty, and significantly reduced final height. Facial features include a broad forehead and short nose with a wide nasal tip, and the majority of patients have small hands and feet. However, many of the clinical features are nonspecific, making diagnosis difficult. In addition, isodisomy may uncover recessive disorders, which may influence the phenotype in maternal uniparental disomy of chromosome 14 (UPD14mat) cases (summary by Ioannides et al., 2014).

Clinical Features

Temple et al. (1991) reported a boy who inherited a balanced 13;14 Robertsonian translocation from his mother. Molecular studies showed that neither chromosome 14 was of paternal origin. The proband had hydrocephalus, bifid uvula, premature puberty, short stature, and small testes. Early motor milestones were delayed, but speech was advanced; intellectual development remained good at 17 years of age, and he was expected to attend university. Temple et al. (1991) stated that this was the first reported case of maternal uniparental disomy of chromosome 14 in humans.

Ioannides et al. (2014) reviewed 51 published cases of Temple syndrome associated with maternal uniparental disomy of chromosome 14 (40 cases), paternal deletions on chromosome 14 (5 cases), or loss of methylation at the intergenic differentially methylated region (IG-DMR; 6 cases). Hypotonia and motor delay were reported in 93% and 83% of cases, respectively. Early puberty was reported in 86% of cases, with mean age of menarche at about 10 years. Small hands (87%) and feet (96%) were frequently reported. Premature birth was common (30%) as were feeding difficulties. There was evidence of mildly reduced intellectual ability, with measured IQs reported between 75 and 95. Obesity was reported in 49% of cases, and 3 patients developed type 2 diabetes. Two patients had recurrent hypoglycemia, 1 of whom was found to be growth hormone-deficient.

Nomenclature

Buiting et al. (2008) suggested the designation 'Temple syndrome' for this disorder because 'Temple was the first to describe a patient with UPD(14)mat and a patient with a DLK1/GTL2 epimutation (Temple et al. (1991, 2007)).'