ESPE Abstracts

Background: Beckwith–Wiedemann Syndrome (BWS) is a clinical and genetically heterogeneous entity encompassing overgrowth and variable manifestations. Early diagnosis of BWS is crucial due to the increased risk for developing embryonal malignancies (mainly below 5 years of age).

Objective: We aimed to screen the presence of underdiagnosed BWS among ‘non-syndromic’ obese children.

Method: We studied 159 children (95 males/64 females) diagnosed with early-onset (<5 years) severe (BMI–SDS >+3 SDS) obesity. A custom-made methylation-specific multiple-ligand-probe-assay (MS-MLPA), with HhaI as a methylation-sensitive restriction enzyme, was used to analyze blood cell DNA methylation at the 11p15.5 region. The assay contains 11 probes, including one for the imprinting-center 1 (IC1) locus (H19) and one for IC2 (KCNQ1). Probes located at fully unmethylated loci were included as technical controls, as well as probes without the HhaI recognition site for methylation quantification.

Results: Hypomethylation at KCNQ1 locus was identified in two patients (60 and 33% methylation decrease respectively). None of them fullfilled the minimum criteria proposed for diagnosing BWS. The patient with 60% methylation impairment, presented no major nor minor criteria for BWS, with suitable birth anthropometry and height and bone age according to her target height and chronological age, respectively. In contrast, the patient with a 33% methylation impairment, presented a more severe, predominantly abdominal obesity (BMI >+8SDS), with pre- (birth length and weight 53 cm and 4.0 kg, respectively) and postnatal macrosomy (height +2.7 SDS), gestational polihydramnios, diastasis recti and advanced bone age (>+1.5 years over chronological age) among proposed BWS diagnostic criteria (one major+three minor). No liver or kidney ultrasonographic abnormalities nor elevation in plasma α-fetoprotein levels were found, but patients had never been tested before their molecular diagnosis.

Conclusion: Some overgrowth syndromes, particularly BWS, can present clinically as early-onset obesity leading to misdiagnosis and misclassification as ‘common’ obesities.