Further Outpatient Care
Routinely monitor somatic growth and development at 3-month intervals.
Further Inpatient Care
Weaning from diazoxide mandates an inpatient fasting study to ensure that the child can maintain euglycemia.
The tumor most commonly associated with Beckwith-Wiedemann syndrome (BWS) is Wilms tumor. [57]
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Once Wilms tumor has been diagnosed in a child, evaluation for a partial nephrectomy is strongly encouraged. See the image below.
Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
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Children with Beckwith-Wiedemann syndrome who develop cancer and are screened in intervals of fewer than 4 months display an average Wilms tumor size of approximately 3.5 cm, as opposed to a size of 11-13 cm in children who are not screened for Wilms tumor.
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Consideration for a partial nephrectomy is important because nonmalignant renal disease and metachronous Wilms tumor carry high risk of morbidity. Imaging findings and medical records of 152 neonates, infants, children, and adults with Beckwith-Wiedemann syndrome (age range, 1 d to 30 y; median age, 15 mo) were retrospectively reviewed by 3 radiologists. [13]
- Correlation to available pathologic material revealed 38 (25%) of 152 patients with Beckwith-Wiedemann syndrome had 45 nonmalignant renal abnormalities, including medullary renal cysts (n=19, 13%), caliceal diverticula (n=2, 1%), hydronephrosis (n=18, 12%), and nephrolithiasis (n=6, 4%).
- Thirty-three (87%) of the 38 patients with nonmalignant renal disease were asymptomatic.
- Clinical manifestations of the remaining 5 patients included urinary tract infections (n=4) and flank pain due to obstructive stone disease (n=1).
- Nonmalignant renal disease was mistaken for Wilms tumor in 2 patients, resulting in unnecessary nephrectomies.
- Seven children (18%) had Wilms tumor and nonmalignant renal disease.
- Children's Oncology Group is considering a submitted protocol for conducting the partial nephrectomy trial in children with Beckwith-Wiedemann syndrome and Wilms tumor.
The second most common cancer occurring in patients with Beckwith-Wiedemann syndrome is hepatoblastoma.
Inpatient & Outpatient Medications
Neonatal hypoglycemia in patients with Beckwith-Wiedemann syndrome tends to be transient. Attempts to taper diazoxide may be initiated in the outpatient setting after age 6 months and then completed with an inpatient fasting study within a few days of discontinuing diazoxide.
Transfer
Maintain airway and euglycemia (with intravenous dextrose) en route to a tertiary care center.
Deterrence/Prevention
Screening for cancer is warranted if early identification of the tumor leads to improved survival and/or decreased morbidity associated with cancer treatment. The 2 most common cancers associated with Beckwith-Wiedemann syndrome (Wilms tumor and hepatoblastoma) meet these criteria.
The authors recommend screening for cancer in children with Beckwith-Wiedemann syndrome, despite the observation that cancer does not develop in most children with Beckwith-Wiedemann syndrome. Cancer develops in approximately 1 in 10 children with Beckwith-Wiedemann syndrome; however, this risk is high enough to warrant cancer screening. The risk of cancer is age-dependent; the risk is higher in patients younger than 4 years, lower in patients aged 5-10 years, and near the baseline risk of cancer in the general population in patients older than 10 years. [14]
Prenatal ultrasonography permits early detection of severely affected patients with Beckwith-Wiedemann syndrome. More critically, prenatal diagnosis allows physicians to anticipate the most serious health consequences associated with Beckwith-Wiedemann syndrome, namely, hypoglycemia and abdominal tumors. [15]
The length of screening intervals for ultrasonographic examination is not well established; however, the authors believe that screening in intervals fewer than 4 months is appropriate. Screening for Wilms tumor using abdominal ultrasonography at intervals no less frequently than every 4 months was been shown in one large series to detect every case of early-stage Wilms tumor.
A false perception is that the screening interval can be increased from 3 months to 6 months to 12 months as a child becomes older. This is not true because Wilms tumor grows too fast to justify screening every 6-12 months. In fact, the authors have several patients who underwent screening every 6 months and were found to have late-stage Wilms tumor.
Using routine abdominal ultrasonography to identify tumors has proven cost effective because physical examination (eg, palpation), even by experienced professionals or well-trained parents, is ineffective for early (small) tumors, which are most amenable to resection. However, in the absence of reliable ultrasonography, physical examination is the next best screening test available.
Repeated ultrasonography remains highly effective for detection of abdominal masses, despite its high cost compared with the cost of physical examination. In patients with tumors identified by ultrasonographic screening, the average size of the tumor was 4 cm, as opposed to 12 cm when palpation alone was used. Prenatal genetic testing is not commercially available.
As with Wilms tumor, hepatoblastoma can be identified using abdominal ultrasonography. However, abdominal ultrasonography does not view the entire liver. Fortunately, alpha-fetal protein (AFP), a protein generated by fetal liver, is a suitable marker for hepatoblastoma. At birth, AFP levels are high and then gradually decline to adult levels by age 10-11 months. However, most infants with hepatoblastoma do not display a declining AFP measurement; rather, their AFP level rapidly increases. In a small case series of 5 patients with Beckwith-Wiedemann syndrome, early stage hepatoblastoma (stage 1) was identified by elevated AFP level after serial evaluation for a maximum 8 weeks. [16]
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AFP levels that increase dramatically but do not continue to drop during the first year of life are worrisome. For example, an AFP level that increases from 18 ng/mL to 180 ng/mL warrants further investigation, as does an AFP level that does not decline by the time the infant is aged 6 months. When such situations occur, the authors recommend repeating the AFP measurement in about 2 weeks and considering imaging studies (eg, liver ultrasonography, CT, MRI). Reports describe several children with Beckwith-Wiedemann syndrome in whom AFP measurements were elevated yet imaging studies did not initially reveal the tumor.
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Hepatoblastoma is also a fast-growing cancer. Because of the fast growth, the authors recommend AFP measurement every 6 weeks and ultrasonography of the liver and kidney every 12 weeks. Liver and renal ultrasonography can be performed at the same time. Unlike the risk of Wilms tumor, the risk of hepatoblastoma declines after 4 years of age; thus, screening with AFP is recommended in patients as old as 4 years. The authors see no value in conducting liver ultrasonography after age 4 years.
As with all screening programs, the physician and family must consider the risk-benefit ratio for the child. The authors recommend screening with AFP level until age 4 years and with ultrasonography until age 8 years, based on the observation that most but not all hepatoblastomas and Wilms tumor occur by these ages. The decision to screen beyond these ages is individual, weighing benefits against the risks. The major risk of screening is misdiagnosis of cancer that results in inappropriate surgery. The authors have experienced 3 such incidents. A cost-effective model describing the costs and benefits of screening for cancer was conducted in this population. Although imperfect, the model, coupled with available data, strongly favors screening for Wilms tumor and hepatoblastoma. [17]
Children with Beckwith-Wiedemann syndrome can develop other cancers, including neuroblastoma, rhabdomyosarcoma, or adrenocortical carcinoma. Fortunately, these cancers are rare in children with Beckwith-Wiedemann syndrome, and screening for these has no proven benefit.
Complications
Medical and surgical complications are possible with treatment of abdominal tumors.
Prognosis
Prognosis is fair and depends primarily on the status of the airway and on aggressive prevention of hypoglycemia.
Patient Education
Instruct parents and caregivers how to perform monthly palpation for abdominal masses. Any unusual finding should prompt professional evaluation.
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Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
