MECP2 duplication syndrome

Overview

MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, seizures that may not improve with treatment, or muscle stiffness (spasticity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately one third of people with this condition cannot walk without assistance. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with almost half succumbing by age 25.

Symptoms

Only males are affected, although female carriers may have some mild neuropsychiatric features, such as anxiety.

MECP2 duplication syndrome is characterized by

  • severe to profound mental retardation
  • infantile hypotonia
  • mild dysmorphic features
  • poor speech development
  • autistic features, seizures
  • Hypotonia
  • As a result of hypotonia, motor development including sitting, crawling, and walking is severely delayed or impaired
  • Recurrent respiratory infections (in 75%)
  • Epilepsy (in 50%)
  • Constipation and/or reflux
  • Ataxia
  • Progressive spasticity (usually noticed in the legs more than the arms)
  • Stereotyped movements of hands
  • Teeth grinding
  • Developmental regression occurs in some boys

Only males are affected, although female carriers may have some mild neuropsychiatric features, such as anxiety.

Causes

MECP2 duplication syndrome is caused by a genetic change in which there is an extra copy of the MECP2 gene in each cell. This extra copy of the MECP2 gene is caused by a duplication of genetic material on the long (q) arm of the X chromosome. The size of the duplication varies from 100,000 to 900,000 DNA building blocks (base pairs), also written as 100 to 900 kilobases (kb). The MECP2 gene is always included in this duplication, and other genes may be involved, depending on the size of the duplicated segment. Extra copies of these other genes do not seem to affect the severity of the condition, because people with larger duplications have signs and symptoms that are similar to people with smaller duplications.

The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. An extra copy of the MECP2 gene leads to the production of excess MeCP2 protein, which is unable to properly regulate the expression of other genes. The misregulation of gene expression in the brain results in abnormal nerve cell (neuronal) function. These neuronal abnormalities cause irregular brain activity, leading to the signs and symptoms of MECP2 duplication syndrome.

Prognosis

The prognosis of Lubs X-linked mental retardation syndrome usually refers to the likely outcome of Lubs X-linked mental retardation syndrome. The prognosis of Lubs X-linked mental retardation syndrome may include the duration of Lubs X-linked mental retardation syndrome, chances of complications of Lubs X-linked mental retardation syndrome, probable outcomes, prospects for recovery, recovery period for Lubs X-linked mental retardation syndrome, survival rates, death rates, and other outcome possibilities in the overall prognosis of Lubs X-linked mental retardation syndrome. Naturally, such forecast issues are by their nature unpredictable.