Williams Beuren syndrome (WBS) is a multisystemic disorder caused by a hemizygous deletion of 1.5Mb on
chromosome 7q11.23 spanning 28 genes. A few patients with larger and smaller WBS deletion have been reported.
They show clinical features that vary between isolated SVAS to the full spectrum of WBS phenotype, associated with
epilepsy or autism spectrum behavior. Here we describe four patients with atypical WBS 7q11.23 deletions. Two carry
B3.5Mb larger deletion towards the telomere that includes Huntingtin-interacting protein 1 (HIP1) and tyrosine
3-monooxygenase/tryptophan 5-monooxigenase activation protein gamma (YWHAG) genes. Other two carry a shorter deletion
of B1.2Mb at centromeric side that excludes the distal WBS genes BAZ1B and FZD9. Along with previously reported cases,
genotype–phenotype correlation in the patients described here further suggests that haploinsufficiency of HIP1 and YWHAG
might cause the severe neurological and neuropsychological deficits including epilepsy and autistic traits, and that the
preservation of BAZ1B and FZD9 genes may be related to mild facial features and moderate neuropsychological deficits.
This report highlights the importance to characterize additional patients with 7q11.23 atypical deletions comparing
neuropsychological and clinical features between these individuals to shed light on the pathogenic role of genes within
and flanking the WBS region.
