MECP2 duplication phenotype in symptomatic females: Report of three further cases

Background: Xq28 duplications, including MECP2 (methyl CpG-binding protein 2; OMIM 300005), have been
identified in approximately 140 male patients presenting with hypotonia, severe developmental delay/intellectual
disability, limited or absent speech and ambulation, and recurrent respiratory infections. Female patients with Xq28
duplication have been rarely reported and are usually asymptomatic. Altogether, only fifteen symptomatic females
with Xq28 duplications including MECP2 have been reported so far: six of them had interstitial duplications while
the remaining had a duplication due to an unbalanced X;autosome translocation. Some of these females present
with unspecific mild to moderate intellectual disability whereas a more complex phenotype is reported for females
with unbalanced X;autosome translocations.
Findings: Here we report on the clinical features of three other adolescent to adult female patients with Xq28
interstitial duplications of variable size, all including MECP2 gene.
Conclusions: Mild to moderate cognitive impairment together with learning difficulties and speech delay were
evident in each of our patients. Moreover, early inadequate behavioral patterns followed by persistent difficulties in
the social and communication domains, as well as the occurrence of mild psychiatric disturbances, are common
features of these three patients.