By Jennifer M. Kalish, MD, PhD, Attending Geneticist, and Evan R. Hathaway, MS, LCGC, Genetic Counselor

Beckwith-Wiedemann syndrome (BWS) is a complex multisystem overgrowth and cancer predisposition disorder that affects about 1 in 10,000 live births. Assisted reproductive technologies (ART) increases the risk to 1 in 1,100 live births. Improved clinical and molecular diagnostic guidelines have been developed with guidance from the BWS Clinic and Registry at CHOP in conjunction with centers throughout Europe.

Several of the cardinal features of BWS, including macroglossia, omphalocele, hyperinsulinism, and increased risk for embryonal tumors, require evaluation and management in the neonatal period. Additional features that would be unlikely to impact neonatal course but can lead to a diagnosis of BWS are facial nevus simplex, nephromegaly, hepatomegaly, placentomegaly, polyhydramnios, ear creases or pits, transient hypoglycemia, umbilical hernia, diastasis recti, and being large for gestational age (LGA).

Macroglossia

Approximately 90% of children with BWS have macroglossia. An enlarged tongue can cause feeding and respiratory issues in the neonatal period and beyond. Infants presenting with macroglossia should undergo a feeding evaluation and polysomnography which can be utilized as an objective measure for obstructive sleep apnea. An evaluation by a plastic surgeon familiar with macroglossia is also necessary to consider the utility of tongue reduction to improve immediate feeding and breathing concerns as well as avoid potential speech development and structural jaw issues in the future.

Hyperinsulinism

While a significant percentage of neonates with BWS have transient hypoglycemia that resolves within the first few days of life, roughly 20% will have prolonged hypoglycemia due to hyperinsulinism (HI) that requires escalated treatment. Neonates with suspected or confirmed BWS should be screened for hypoglycemia, and infants with low plasma glucose levels should be evaluated by an endocrinologist familiar with HI. Treatment of HI can include medical therapies, pancreatectomy, and/or continuous feeds.

Embryonal Tumors

As children with BWS have an increased risk for developing embryonal tumors, specifically Wilms tumor and hepatoblastoma, tumor screening should be initiated immediately for any baby suspected to have BWS. The screening guidelines for BWS are complete abdominal ultrasounds every 3 months and serum alpha-fetoprotein (AFP) levels until the fourth birthday, followed by renal ultrasounds every 3 months until age 7.

Omphalocele

No specific recommendations for omphalocele management exist for babies with BWS, and standard practices should be observed.

Careful and timely consideration of the recommendations is necessary for comprehensive care of neonates with BWS.

One of the many newborns with BWS we have cared for at CHOP presented prenatally with an omphalocele on a 12-week ultrasound. His mother was referred to our Center for Fetal Diagnosis and Treatment at the time, and a diagnosis of BWS was highly suspected due to the additional prenatal features of being LGA along with enlarged kidneys and liver. The child was born via caesarean section at 34 weeks after his mother presented to our hospital’s Garbose Family Special Delivery Unit with premature rupture of membranes. After birth, he was immediately transferred to our Harriet and Ronald Lassin Newborn/Infant Intensive Care Unit (N/IICU) where a clinical diagnosis of BWS was made based on features of omphalocele, LGA, macroglossia, hypoglycemia, and facial nevus simplex. This diagnosis was confirmed through molecular testing. Due to prolonged hypoglycemia, Endocrinology was consulted, and he was confirmed to have hyperinsulinism. His blood glucose levels were maintained via total parenteral and enteral feeds with a background glucose infusion rate until he passed a cure fast prior to discharge. During his initial N/IICU stay he was evaluated for feeding and breathing concerns due to his enlarged tongue, and it was determined that an early tongue reduction was not required. He later had a hemiglossectomy at 13 months of age. His first tumor screening through abdominal ultrasound and AFP was completed on the second day of life and was not concerning for any lesions. However, at approximately one and half months old, when the child was close to being discharged from the N/IICU, his AFP was noted to increase and a new liver mass was determined to be a hepatoblastoma. He underwent chemotherapy prior to surgical resection of the tumor and omphalocele repair.

Our experience with this child and many other children with BWS has enabled us to improve our clinical management of the neonate with BWS. In an effort to streamline our own practices and provide a resource for other institutions, we have developed a pathway describing the necessary evaluations and interventions for newborns suspected to have BWS. The pathway will be available in a Web-based format later this year.

For more information on BWS including ongoing research, the BWS Registry, and educational resources for families and providers please our research website or read more about the BWS clinic.