P-227: WAGR syndrome with early metabolic dysfunction: the importance of genetic diagnosis and multidisciplinary care
R Dobrovolskiene, E Jasinskiene, R T Preiksa, I Stankute, R Traberg, R VerkauskieneAbstract
Introduction
WAGR syndrome is a rare contiguous gene deletion disorder characterized by the classical tetrad: Wilms tumor, aniridia, genitourinary anomalies, and a spectrum of developmental delays. It is caused by a deletion on chromosome 11p13, typically involving critical genes such as WT1 and PAX6.
Objectives
To present a rare clinical case of WAGR syndrome with multisystem involvement, including endocrine and metabolic abnormalities.
Methods
A 4-year-old girl was referred to a pediatric endocrinologist due to rapid weight gain and metabolic disturbances. Her anthropometric measurements were: height 100.2 cm (10th–25th percentile), weight 19 kg (75th–90th percentile), and BMI 18.92 kg/m2 (approaching the 97th percentile). Laboratory evaluation revealed fasting hyperglycemia (up to 5.84 mmol/L) with insulin resistance (HOMA-IR 3.63), and central hypothyroidism (low TSH and low FT4). Previous medical history: she was the first child in the family. Aniridia was diagnosed shortly after birth. At the age of 1.5 years, she was diagnosed with nephroblastoma (Wilms tumor) of the right kidney. Given the suspicion of a rare syndromic condition, the patient was referred for genetic evaluation.
Results
Genetic testing identified a pathogenic heterozygous deletion >7 Mb on chromosome 11p13, encompassing multiple genes including PAX6, WT1, BDNF, FSHB, DCDC1, ELP4, RCN1, HIPK3, and CD44. Haploinsufficiency of WT1, PAX6, and BDNF is considered central to the patient’s phenotype, contributing to tumor predisposition, ocular abnormalities, and neurodevelopmental and metabolic features.
Conclusions
This case highlights the critical role of genetic testing in patients with congenital anomalies and multisystem involvement. WAGR syndrome may also present with endocrine and metabolic disturbances, including obesity, insulin resistance, and hypothyroidism. Early diagnosis and coordinated multidisciplinary management are essential to optimize clinical outcomes.