Endocrine Abstracts

Congenital imprinting disorders (IDs) are a group of rare conditions affecting growth, metabolism and development caused by aberrant expression of imprinted genes in a parent-of-origin dependent manner. The internationally recognised IDs are Prader Willi Syndrome (PWS), Angelman Syndrome (AS), Beckwith Wiedemann Syndrome (BWS), Silver Russell Syndrome (SRS), Temple Syndrome (TS14), Pseudohypoparathyroidism (PHP), Transient Neonatal Diabetes Mellitus (TNDM) and Kagami-Ogata Syndrome (KOS14). Given their broad clinical overlap and complex underlying molecular mechanisms, diagnosis can be challenging. Mechanisms causing IDs include methylation defects, uniparental disomy, chromosomal imbalances and mutations in imprinted genes. Such mechanisms can be associated with factors such as assisted reproductive technology and advanced maternal age and it is postulated that frequency of IDs is increasing. Few population studies have been performed worldwide and for the less common IDs, frequency is unknown. We examine incidence, prevalence, genotype and clinical characteristics of IDs in Irish children. 4 years of prospective case ascertainment via the Irish Paediatric Surveillance Unit identified 47 new cases of IDs yielding an incidence of 0.9 per 100,000 in Irish children. To date, almost 200 prevalent cases have been identified via review of genetic laboratory records, paediatrician reporting and database searches at Children’s Health Ireland. PWS accounts for more than one third of these while TNDM, PHP, TS and KOS are very rare. Genotype and clinical characteristics were examined through review of genetic records, parent questionnaires and retrospective chart review. >90% cases of PWS and BWS had genetic testing in the first 6 months of life reflecting high levels of recognition. Children with SRS and AS were older at time of molecular diagnosis. Rates of delivery by caesarean section, prematurity, low birth weight and admission to the neonatal unit are higher than the national averages in this cohort. The number of health professionals who have been involved in care ranged from 2 to >15. Studying the epidemiology of these conditions and their associated burden of medical care is imperative to the planning and delivery of health services to these patients.