BACKGROUND: Global developmental delay and mental retardation are associated 
with X-linked disorders including Hunter syndrome (mucopolysaccharidosis type 
II) and Fragile X syndrome (FXS). Single nucleotide mutations in the iduronate 
2-sulfatase (IDS) gene at Xq28 most commonly cause Hunter syndrome while a CGG 
expansion in the FMR1 gene at Xq27.3 is associated with Fragile X syndrome. Gene 
deletions of the Xq27-28 region are less frequently found in either condition 
with rare reports in females. Additionally, an association between Xq27-28 
deletions and skewed X-inactivation of the normal X chromosome observed in 
previous studies suggested a primary role of the Xq27-28 region in 
X-inactivation.
CASE PRESENTATION: We describe the clinical, molecular and biochemical 
evaluations of a four year-old female patient with global developmental delay 
and a hemizygous deletion of Xq27.3q28 (144,270,614-154,845,961 bp), a 10.6 Mb 
region that contains >100 genes including IDS and FMR1. A literature review 
revealed rare cases with similar deletions that included IDS and FMR1 in females 
with developmental delay, variable features of Hunter syndrome, and skewed 
X-inactivation of the normal X chromosome. In contrast, our patient exhibited 
skewed X-inactivation of the deleted X chromosome and tested negative for Hunter 
syndrome.
CONCLUSIONS: This is a report of a female with a 10.6 Mb Xq27-28 deletion with 
skewed inactivation of the deleted X chromosome. Contrary to previous reports, 
our observations do not support a primary role of the Xq27-28 region in 
X-inactivation. A review of the genes in the deletion region revealed several 
potential genes that may contribute to the patient's developmental delays, and 
sequencing of the active X chromosome may provide insight into the etiology of 
this clinical presentation.