Prader-Willi-like phenotype in fragile X syndrome

A 3-year-old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical-cytogenetic-molecular grounds, Prader-Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR-1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader-Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader-Willi syndrome is negative. Clinical behavior can be of help.