Beckwith-Wiedemann Syndrome Associated with Congenital Hypothyroidism in a Preterm Neonate: A Case Report and Literature Review

J Perinatol. 2009;29(6):455-457. 

In This Article

Abstract and Case Report

Abstract

This report describes for the first time the association of Beckwith-Wiedemann syndrome (BWS) and hypothyroidism in a 25 weeks preterm neonate. Antenatal diagnosis of exomphalos in association with postnatal transient hypoglycemia and macroglossia formed the basis of the diagnosis of BWS. Primary hypothyroidism was detected on routine Guthrie card examination. Molecular DNA analysis demonstrated biparental inheritance of chromosome 11p15.5. Dosage analysis of differently methylated region showed evidence of loss of maternal methylation at KvDMR1.

Case Report

A male infant was born prematurely at 25 weeks gestation weighing 830 g (50th centile) to unrelated Black Caribbean parents. The infant's mother was 34 years old and had previously lost an infant at 2 days of age as a result of group B streptococcus septicemia. An exomphalos was detected on the 20-week anomaly ultrasound scan, which contained bowel and mesentery. There were no other major malformations (Figure 1a and b). At delivery, the Apgar score was 7 and 9 at 1 and 5 min, respectively. The infant was electively intubated and surfactant was administered.

Figure 1.

(a) and (b) show 20-week anomaly scan. The straight arrow in (a) and (b) indicates the exomphalos containing part of the bowel and its mesentery, the interrupted arrow in (b) points to the gastric bubble in the abdominal cavity.

After birth, an exomphalos minor was confirmed. Further examination revealed macroglossia, but no other organomegaly. Detailed echocardiogram revealed no structural heart abnormalities. Abdominal ultrasound scan demonstrated normal liver size and texture and normal kidneys.

The blood glucose level was < 2 mmol l-1. The infant was treated for hypoglycemia in the first few days of life. He required increasing concentrations of glucose infusion up to 20 mg kg-1 min-1 to maintain euglycemia. Initially, the infant was on conventional ventilation. However, as a result of worsening lung disease, high frequency oscillation was used till his care was withdrawn at 25 days of life. Respiratory deterioration was compounded by a large 2.4 mm persistent ductus arteriosus, which failed to close despite two courses of ibuprofen therapy. Vasopressor resistant hypotension required maximal ionotropic support and parenteral hydrocortisone.

The infant developed acute renal failure with rising serum potassium levels and low urine output, which was treated by an intravenous infusion of salbutamol, insulin/dextrose, calcium resonium and sodium bicarbonate. He developed late onset coagulase negative staphylococcus septicemia with meningitis on day 12 of life; this was treated with intravenous vancomycin and piptazobactam. He remained on total parenteral nutrition and never established entral feeds. On day 14 of life he developed 2:1 heart block. Thyroid function tests were requested. These revealed high thyroid stimulating hormone (TSH) levels of > 100 mU l-1 and low levels of triiodothyronine (T3; 3 pmol l-1), which is indicative of primary hypothyroidism. He was started on an intravenous infusion of T3. High blood spot TSH concentration of 83 mU l-1, equivalent to 160 mU l-1 plasma (normal range up to 10 mU l-1) was also detected on routine Guthrie card examination, confirming the presence of congenital hypothyroidism. There was no history of thyroid disease in his pedigree.

In view of the significant deterioration in the infants' clinical condition, his care was withdrawn on day 25 of life. Chromosomal analysis revealed normal male karyotype. Molecular DNA analysis using polymerase chain reaction (PCR) demonstrated biparental inheritance of chromosome 11p15.5 with no evidence of mosaic isodisomy. Dosage analysis of differently methylated region showed evidence of loss of maternal methylation at KvDMR1 consistent with a diagnosis of Beckwith-Wiedemann syndrome (BWS). Molecular analysis was performed by PCR amplification of the KvDMR1 region following bisulfite treatment. The PCR product was digested with the restriction enzyme, BstU1, to enable differentiation between the parental alleles. The digested products were resolved by gel electrophoresis. Postmortem examination was declined by parents.

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