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

Abstract

BackgroundXq28 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.FindingsHere 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.ConclusionsMild 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.

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

“…). Moreover, among these seven patients, three were mildly affected, one was moderately affected, and three, including the twins, had severe to profound ID (Table ). The mean size of the duplicated segment in the reported patients with an intraC dupMECP2 was 506 kb (min.…”

“…Here, we report on a new series of six sporadic females with interstitial dupMECP2 in order to further delineate the clinical spectrum of dupMECP2 in females and further discuss the difficulties of genetic counselling in such cases. These patients were identified among 99 patients with a dupMECP2 in France and Switzerland (two patients), and increased to 20 the number of females reported in the literature, compared with 140 male patients . A recruitment bias is probable, due to the fact that the affected females are probably more often reported because they are uncommon.…”

“…To date, 14 female patients with an intraC dupMECP2 of various sizes have been described in the literature . Among these, seven (50%) had inherited the duplication from their mother (Table , Figs and ).…”

“…Among these, seven (50%) had inherited the duplication from their mother (Table , Figs and ). Among these seven patients with an inherited intraC dupMECP2, including twins , four had an affected male in the family, and all of the carrier mothers were asymptomatic except one who had learning difficulties and depression (Table and Fig. ).…”

Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration

“…With the clinical application of array-CGH, Xq28 microduplications, including MECP2 gene, emerged as one of the most common genomic rearrangements in males with developmental delay [3]. …”