Endocrine Abstracts

JOINT373

Introduction: Beckwith–Wiedemann syndrome (BWS) is a rare syndrome with features of overgrowth, macroglossia, abdominal wall defects, hemihypertrophy and enlarged abdominal organs. It is caused by genetic or epigenetic defects within the chromosome 11p15.5 region which contains imprinted genes that are strong regulators of fetal growth. Molecular diagnosis of BWS is important because of different degrees of predisposition to embryonal tumours in various subtypes. Presentation of BWS is widely variable and may be associated with adrenal involvement. Congenital adrenal hyperplasia (CAH) is the leading cause of atypical genitalia in the female newborn. An elevated blood level of 17-hydroxyprogesterone (17-OHP) indicates 21-hydroxylase deficiency, and is used in neonatal screening of CAH to prevent adrenal crisis and early neonatal death. Previously, BWS was not a recognized cause of false positives for CAH screening but this has been reported recently in some cases of BWS. This case is presented because of a similar presentation.

Case description: A late preterm (36weeks gestational age) female presented at the 3^rd hour of life with anterior abdominal wall defect and swelling. Examination revealed coarse facial features, macroglossia, omphalocoele major, prominent labia majora with hyperpigmented and enlarged clitoris. Cardiorespiratory examination was essentially normal. Weight was (3600g) greater than the 97^th percentile for age and sex, with length (50cm) and occipitofrontal circumference (32cm) at 95^th and 50^th percentiles respectively. No hemihypertrophy was noticed. Bedside blood glucose was low (30mg/dl[1.7mmol/l]). Other serum investigations revealed low cortisol, elevated testosterone and 17-hydroxyprogesterone. Pelvic ultrasound scan (USS) showed female internal genitalia suggesting CAH. She was commenced on hydrocortisone while omphalocele major was managed conservatively. There was no enlargement of the adrenal glands and no tumours seen on abdominal USS. Genetic analysis showed hypomethylation at KCNQ1OT1:TSS-DMR (IC2) within 11p15.5 confirming a diagnosis of BWS. Clitoromegaly resolved at 6 months of age with normal pigmentation of the external genitalia. Steroids have been tailed off and repeat cortisol, testosterone and 17-hydroxyprogesterone are normal. Patient is being monitored as per the protocol for BWS with IC2 mutation (clinical assessment and USS in response to signs and/or symptoms or parental concern).

Conclusions: Beckwith-Wiedemann syndrome can present with features suggestive of CAH. Monitoring and genetic testing is essential for confirmation. In view of risk of adrenal crisis in infants with CAH, it may be better to err on the side of caution by commencing hydrocortisone especially when genetic screening is unavailable and tail off therapy if no longer needed.