Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections.
Six children with GD (age: 36.8 ± 14.1 months, 5 boys) having mutations in MID1, CDK4, SFRP1, EN2, RXRG-GLRB, or MECP2, and five children with typical development (TD, age: 38.5 ± 20.5 months, 4 boys) underwent a 3 Tesla MRI including diffusion weighted imaging (DWI).
One patient's symptoms suggest an extension of the known spectrum of MECP2 associated phenotypes to include global developmental delay with obsessive compulsive disorder and attention deficit hyperactivity disorder.
Furthermore, a complex duplication spanning of the MECP2 gene was identified in two brothers who presented with developmental delay and intellectual disability.
Methyl-CpG binding protein 2 gene (MECP2) testing is indicated for patients with numerous clinical presentations, including Rett syndrome (classic and atypical), unexplained neonatal encephalopathy, Angelman syndrome, nonspecific mental retardation, autism (females), and an X-linked family history of developmental delay.
Males with duplication of the Xq28 region, including methyl CpG-binding protein 2 (MECP2), exhibit a characteristic phenotype, including developmental delay, intellectual disability, limited or absent speech, limited or absent ambulation, and recurrent respiratory infections.
We sequenced MECP2 in 51 females with various clinical presentations, including developmental delay, autism, atypical and classical RTT, referred to our laboratories for testing.
Rett syndrome (RS) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2 (Xq28) and characterized by normal development until 6-12 months of age, followed by regression with loss of acquired skills, gradual onset of microcephaly, stereotypic hand movements and psychomotor delay.
Although the etiology of the infections is not understood, we recommend considering MECP2 dosage studies and a genetics referral in individuals with severe developmental delay and neurologic findings, especially when a history of recurrent respiratory ailments has been documented.
This report supports broadening the phenotype of patients who should be considered for MECP2 mutation analysis to include cases of developmental delay and hypotonia without evidence of an initial period of normal development.