Case Report: Beckwith-Wiedemann syndrome with congenital heart disease

Introduction

Chromosome defects cause the Beckwith-Wiedemann syndrome (BWS) in genetic mutation at 11p15. It is prone to embryonal tumors such as Wilms tumor, hepatoblastoma, and neuroblastoma in the first seven years of life.¹ At birth, macroglossia, a defect in the abdominal wall, and hypoglycemia are the most typical signs and symptoms seen in BWS. In a patient presenting with hyperinsulinemia not responding to treatment, BWS should be suspected.²

During antenatal visits, the mother can undergo an investigation like amniocentesis or chorionic villus sampling. This diagnostic tool is only followed in some primigravida in India. It is recommended only when a BWS child is in the family. Ultrasonic studies can determine the renal function or the presence of embryonal tumors, omphalocele, and macroglossia. On ultrasonography, placental mesenchymal dysplasia and polyhydramnios can be suspected as BWS. Congenital heart disease is commonly associated with BWS. Pathogenesis between PDA (patent ductus arteriosus) and BWS is not known. It is found that PDA amniocentesis is seen in various human genetic syndromes, chromosomal aberrations, or single-gene mutations.³

Medical and surgical treatment is a way to manage BWS. Medical management starts in neonatal periods in screening for hypoglycemia, which should be taken immediately after birth and monitored before discharge. Scanning for tumors through ultrasonography is initiated if BWS is diagnosed or suspected.

Guidelines given by the American Association for Cancer Research Childhood Cancer Predisposition Workshop (AACR-CCPW) include abdominal ultrasound after diagnosis every 90 days til four years of age, and AFP (alfa fetoprotein) screening is mandatory for diagnosed patients of BWS till seven years of age which should be done every three months, to prevent complication.⁴

Surgical treatment includes the need for surgery for abdominal wall defects. An example is omphalocele, which is done early in the neonatal period. Tongue reduction surgery for macroglossia depends on the patient’s clinical status, including sleep apnea, feeding problems, respiratory difficulties, speech, and orthodontic problems. Surgical treatment has excellent and favorable outcomes before two to three years of life. Because of long-term illness, patients’ behavioral, emotional, and psychosocial development is hampered. This part of treatment is always neglected, so early psychological assessment must be done for long-term benefits.⁵

BWS is seen in 1 in 10,400 to 13,800 cases, and the association between BWS and congenital heart disease is not reported in the literature despite an extensive search. Therefore, we wanted to draw attention to this rare case report.⁶

Case report

Patient information

An 11-month-old female child was referred to the pediatric ward for macroglossia, tachypnea, chest retraction, and not feeding correctly with no history of cyanosis or signs of developmental delay (Figure 1).

Figure 1. Macroglossia with chest retraction in patients of BWS.

The patient was born via elective cesarean section at 37 weeks to a primigravida mother with no history of previous abortion and no history of leaking or bleeding per vagina. The mother had no history of diabetes or hypertension during pregnancy. The weight of the baby was 3.5 kg outside the present center. Because of macroglossia since birth, pediatricians diagnosed her with Beckwith-Wiedemann syndrome. Antenatal history was uneventful. Ultrasonography was done twice during pregnancy, but macroglossia was not recognized. No history of neonatal intensive care unit (NICU stay). There is no family history of similar complaints and no history of birth or congenital anomalies in the family. The mother narrated that the patient has frequent fever, cold, and cough episodes after two months of life. She was taken to a local practitioner, where she was given antihistamines and paracetamol for cold, cough and fever which was used to get relief for a short period of time. Due to frequent episodes of cough and cold, she was referred to the private pediatric center, where the pediatrician noted a continuous murmur on the upper left sternal border, and an echocardiogram scan (2D ECHO) was done, which showed signs of PDA (Figure 2).

Figure 2. ECHO showing PDA.

Considering the need for closure, the patient was transferred to our center. On examination, body temp was 37C, heart rate was 160/min, and oxygen saturation was 94%. No cyanosis or abdominal wall opening was seen. The abdominal examination and central nervous system (CNS) examination were normal. Anaesthesia fitness was done. Hb-9.5, TLC-7300, platelets 3 lakhs, and blood sugar 80mg/dl, which was normal. Chest radiography showed cardiomegaly. Ultrasonography (USG) of the abdomen and computed tomography (CT scan) were normal. Magnetic resonance imaging (MRI) of the brain was normal. 2D ECHO showed signs of a 4 mm PDA (Figure 2). Devise closure was done, and the patient was shifted to the pediatric intensive care unit (PICU). The procedure was performed successfully without any complication. The patient was discharged 15 days after surgery. Parents were explained about the diagnosis and the risk factors associated with BWS. During our discussions with parents about the long-term follow-up and potential complications that can arise in the future, we noticed that some of them were feeling anxious and fearful. Our healthcare professionals recognized this and took the time to provide them with extra support and empathy. It’s important to ensure that parents have the resources they need to cope with the challenges.

The patient was observed for developmental milestones during follow-up, which were found normal for their age. Additionally, abdominal examinations were conducted to check for organomegaly, and abdominal ultrasound and pelvis were repeated every three months during the follow-up period. Diagnosed patients of BWS must undergo alpha-fetoprotein (AFP) screening until they are seven years old, which should be done every three months to prevent complications. These protocols were followed in the present case report, as recommended by healthcare organizations.

Discussion

A genetic mutation of chromosome defects at 11p15 causes Beckwith-Wiedemann syndrome. Genetic evaluation should be done for diagnosis. A study by Schneid H, Vazquez MP, et al. showed that a genetic analysis on 11p15 chromosomes and its change in mutation could diagnose BWS. This test was not done in the present case report because of non-availability.⁷

A study by Kathleen H. Wang et al. showed that neonatal hypoglycemia is common in patients diagnosed with BWS. It is generally temporary and ends within a few days, but in some cases, persistent hyperinsulinism (HI) can occur early in life. In the present case report, hypoglycemia was not recorded during the neonatal period or followup, opposite to the study.⁸

In our case report, we observed macroglossia, a commonly seen symptom in patients with BWS, as Paganini L et al. demonstrated during their studies.⁹

The patient with macroglossia should undergo surgery before the age of two years, according to a study conducted by Wang KH, Kupa J et al. Dentists need to monitor the patient’s teeth eruption after surgery. The present research recommended surgery for the patient and referred them to a dentist for evaluation.¹⁰

In a recent case report, a higher incidence of congenital heart disease was associated with BWS, which aligns with a study conducted by Elliott M. et al. and Pettenati MJ. Healthcare providers must be aware of this potential association in patients with BWS. The present case report recommends further evaluation for CHD in patients with BWS.¹¹ It is seen that patients with BWS have normal milestone development. In the study, Kalish JM et al. showed that patients with BWS usually have normal gross and fine motor development, similar to the present study.¹²

Healthcare providers need to be aware of the potential association between BWS and childhood tumors, as highlighted in the study by Mussa A et al. The most common tumors associated with BWS are Wilms and hepatoblastoma, while neuroblastoma, rhabdomyosarcoma, and adrenal carcinoma are less common. However, it is worth noting that no tumors were observed in the present case report, which contrasts with the findings.¹³

Brioude et al.¹⁴ in the expert consensus document ‘Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome’ recommended the guidelines by the American Association for Cancer Research Childhood Cancer Predisposition Workshop (AACR-CCPW), which were followed in the present case report.

Being diagnosed with BWS can have a significant impact on patients and their families. As Meijer S.A. et al. noted, the increased risk of tumors and the need for ongoing monitoring can lead to heightened psychological and social stress. This can be particularly difficult for families as children grow older. The present case report showed that anxiety and fear about the child’s disease were present in the parents, underscoring the need for healthcare providers to be aware of these potential psychological impacts and provide support as needed.¹⁵

In conclusion, physicians and society must understand the impact of rare disorders like BWS and their potential association with PDA. Regular screening for tumors and following guidelines from organizations such as AACR-CCPW are essential for patients with BWS. It is also crucial for healthcare providers to be aware of the potential psychosocial effects of BWS on patients and their families and provide necessary support. Timely intervention can be critical in addressing any emotional or behavioral issues.