MECP2 triplication in 3 brothers – A rarely described cause of familial neurological regression in boys

Male patients with large duplications of the methyl CpG-binding protein 2 (MECP2) gene have been identified with a characteristic phenotype consisting of infantile hypotonia replaced by spasticity, developmental delay, severe mental retardation and recurrent respiratory infections. Only one patient with MECP2 triplication, with a more severe phenotype has been reported so far. We report three brothers of unrelated parents with MECP2 triplication. Their phenotypic features include macrocephaly with large ears, infantile hypotonia, developmental delay, significant constipation, recurrent severe respiratory tract infections from early childhood, and seizures followed by neurological regression in late childhood. Our cases indicate that MECP2 triplication is similar to or more severe than that of MECP2 duplication syndrome.

► We describe three brothers with MECP2 triplication.
► Their facial features include macrocephaly and large ears.
► They had hypotonia, developmental delay, constipation and respiratory infections.
► In later childhood, seizures and neurological regression occur.
► MECP2 triplication is similar or more severe than MECP2 duplication.