Introduction: Prompt diagnosis in Prader-Willi syndrome (PWS) is important for counselling the family and thus pre-empt the hyperphagic phase of the condition.
Objectives: To determine the key diagnostic features of PWS during the perinatal period and hence recommend strategies to ensure early diagnosis.
Study design: Retrospective case note review with prospective questionnaire survey of birth details for the affected child and healthy siblings in which mothers scored fetal movements on a scale of 1 (low) to 5 (high).
Results: Between 1991 and 2015 incluive 90 subjects (54M:36F) with PWS were seen in a multidisciplinary clinic. Cause was paternal deletion (56), maternal disomy (26), imprinting centre mutation (2), translocation/deletion (1), mutation-negative (1), tested elsewhere (5). Mean maternal/ paternal ages for disomic patients were 34.6/34.6 years, significantly older than for deletion at 26.4/29.6 years (P<0.001 & 0.004). PWS pregnancies featured polyhydramnios in 10/34 (29%), breech presentation in 15/53 (28%), and caesarean section delivery in 38/86 (44%). Median (range) birthweight and gestation for patients cf siblings were 2.76 (1.183.99) cf 3.3 (3.14.9) kg; and 39 (3043) cf 40 (3342) weeks, with prematurity (<37 weeks gestation) in 21 (23.6%) and low birthweight (<2500 g) in 28 (32%) of PWS patients. Median (range) fetal movement scores were 1(14) (n=80) for PWS cf 3(15) (n=94) siblings (p<0.001). Median (range) duration of nasogastric feeding and hospital stay was 30.5 days (2 days1.3 years) and 27 days (0 days2 years). Median (range) time to clinical/molecular genetic diagnosis (available≥1991) was 2.5 month (1 day46 years)/10 month (4 day46.5 years). Stratifying by year of birth <1980, 198089, 199099, 200009, and >2010 showed significant improvement in median time (days) to clinical/molecular diagnosis: 1862/8395, 97/3577, 74/73, 19/60 and 7/14 days (P<0.001). However from 20002015 inclusive clinical diagnosis was >28 days in 11 and >1 years in five patients.
Conclusions: Despite the overlap in features with prematurity, diagnosis of PWS can and should be made within days of birth if the key features, mostly hypotonia-related but including cryptorchism in males, are recognised and actively sought. Neonatal paediatricians need to be fully aware of the perinatal features of PWS, including a history of reduced fetal movements, so that unnecessary investigations such as MRI brain scan and muscle biopsy can be avoided.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology