Systematic Review of Females With Intellectual Disability and MECP2 Duplication.

MECP2

Full MECP2 duplication (tandem, unbalanced autosomal translocation or other terminal duplication); severity modulated by rearrangement type and X-inactivation

This registered systematic review (PROSPERO CRD420250652426) of PubMed, EMBASE and Google Scholar, with individual participant data extraction, compiles females with a full MECP2 duplication and intellectual disability, compared with a published male dataset. Of 590 full texts, 41 unique records were included: tandem duplications (59%), unbalanced autosomal translocations (32%), other terminal duplications (7.3%) and one triplication. Females with tandem duplications mostly showed skewed X-inactivation (14/18 reports), mild-to-moderate developmental delay, partially retained speech and ambulation, and fewer neurological and systemic manifestations than males. Conversely, females with unbalanced translocations or other terminal duplications had severe intellectual disability, absent speech (5/9 reports) and severe epilepsy (drug-resistant epilepsy in 8/16 reports), resembling male MECP2 duplication syndrome.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

When counselling a girl with an MECP2 duplication, the type of rearrangement matters as much as the duplication itself: looking for an unbalanced translocation and studying X-inactivation guide prognosis. The synthesis rests on 41 published cases, with a likely publication bias towards symptomatic forms. It is a reminder that CNV analysis on exome/genome benefits from specifying the structure of the gain (tandem or terminal), not just the copy number.

Analysis by Dr Thibaut Benquey