Williams-Beuren syndrome is a common chromosome microdeletion syndrome. Early diagnosis and treatment are very helpful for patients and their families. This study identified the chromosome karyotype in one fetus with ultrasonography abnormalities and three children with developmental disorders from four families. This provided guidance for subsequent pregnancy and prenatal diagnosis by using routine G-banding chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (arrayCGH). In one amniotic fluid sample from a pregnant woman with fetal abnormalities on an ultrasound screen and three peripheral blood samples from three children with developmental disorders, the decreased signal of ELN gene probes at 7q11.23 and heterozygous deletions at 7q11.23 were detected by MLPA and array-CGH analysis. The laboratory genetic tests of amniotic fluid samples were normal when the mothers from the four families became pregnant again. It was concluded that MLPA and array-CGH are rapid and accurate tools for the diagnosis of Williams-Beuren syndrome and can provide more information for clinical genetic counseling.