Abstract
The 22q13.3 deletion syndrome has been widely reported, with a known phenotype including
global developmental delay, normal to accelerated growth and a characteristic facial
appearance. A duplication syndrome involving this region has also been reported, with
a somewhat more variable phenotype including psychomotor retardation, growth restriction,
characteristic facial appearance differing from that seen in the deletion syndrome,
and multiple malformations. The majority of reported patients have terminal duplications,
with only three previous reports of interstitial duplication of the region. Herein
we report a young woman with a de novo 569 kb interstitial duplication of 22q13.2 and short stature, speech and language
impairment, refractive amblyopia, menorrhagia and facial dysmorphism. Comparison of
her phenotype to previously reported patients with interstitial duplications reveals
common traits including growth restriction, craniofacial anomalies and developmental
delays. Included in the duplicated region is the gene EP300, mutations and deletions of which are implicated in Rubinstein-Taybi syndrome and
thyrotroph embryonic factor, which has been proposed to be related to the pituitary
hypoplasia seen in one patient with a large duplication, and several other genes without
clear relation to disease.
Keywords
Copy number variation - microduplication - speech and language impairment - array
comparative genomic hybridization
