Maternal Uniparental Disomy 14 (Temple Syndrome) as a Result of a Robertsonian Translocation

Abstract

Maternal uniparental disomy of chromosome 14 (upd(14)mat) or Temple syndrome is an imprinting disorder associated with a relatively mild phenotype. The absence of specific congenital malformations makes this condition underdiagnosed in clinical practice. A boy with a de novo robertsonian translocation 45,XY,rob(13;14)(q10;q10) is reported; a CGH/SNP array showed a loss of heterozygosity in 14q11.2q13.1. The final diagnosis of upd(14)mat was made by microsatellite analysis, which showed a combination of heterodisomy and isodisomy for different regions of chromosome 14. Obesity after initial failure to thrive developed, while compulsive eating habits were not present, which was helpful for the clinical differential diagnosis of Prader-Willi syndrome. In addition, the boy presented with many phenotypic features associated with upd(14)mat along with hypoesthesia to pain, previously unreported in this disorder, and bilateral cryptorchidism, also rarely described. These features, as well as other clinical manifestations (i.e., truncal obesity, altered pubertal timing), may suggest a hypothalamic-pituitary involvement. A detailed cytogenetic and molecular characterization of the genomic rearrangement is presented. Early genetic diagnosis permits a specific follow-up of children with upd(14)mat in order to optimize the long-term outcome.

Association of BMI with Linear Growth and Pubertal Development

“…As noted in our observations and in other studies , higher prepubertal BMI is associated with earlier pubertal development, possibly through increased secretion of adipokines (e.g., leptin) that may trigger activity of the gonadotrophin‐releasing hormone pulse generator . In addition, some genetic signals may influence both BMI and pubertal development . Earlier pubertal development typically leads to earlier cessation of linear growth and, therefore, smaller adolescent height gains.…”

Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG)

“…53 Maternal UPD14 is the most widely recognized cause of TS; it results in loss of expression of all paternally expressed genes (DLK1, RTL1, and DIO3) and overexpression of maternally expressed genes (noncoding RNAs GTL2/MEG3, MEG8, RTL1as, and additional micro-RNAs [miRNAs] and small nucleolar RNAs [snoRNAs]) at chromosome 14q32.2. 54,55 In rare cases, maternal UPD14 has been reported in association with mosaicism, 56 Robertsonian translocations, 57 and sSMC. 58 Paternal UPD14 and Kagami-Ogata syndrome Kagami-Ogata syndrome (KOS, MIM 608149) is characterized by a severe phenotype with polyhydramnios, large omphalocele, thoracic dysplasia (coat-hanger sign on X-rays) with respiratory failure, abdominal wall defects, poor growth, developmental delay, and facial abnormalities including full cheeks and protruding philtrum.…”

Clinical management of pregnancies with positive screening results for rare autosomal aneuploidies at a single center

“…However, fetal loss due to unexplained vaginal bleeding was present in this pregnancy. As described previously, UPD is associated with multiple imprinting disorders, such as transient neonatal diabetes mellitus, 22 Russell-Silver syndrome, 23 Beckwith-Wiedemann syndrome, 24 maternal and paternal UPD (14) syndromes, 25,26 Angelman syndrome, Prader-Willi syndrome, 27 and UPD(20) maternal and paternal syndrome. 28,29 Other reports have also shown that aneuploidies at NIPT have a high risk of fetal UPD.…”