MECP2 Gene

MECP2-related severe neonatal encephalopathy is a neurological disorder that primarily affects males and causes brain dysfunction (encephalopathy). Affected males have a small head size (microcephaly), poor muscle tone (hypotonia) in infancy, movement disorders, rigidity, and seizures. Infants with this condition appear normal at birth but then develop severe encephalopathy within the first week of life. These babies experience poor feeding, leading to a failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MECP2-related severe neonatal encephalopathy have severe to profound intellectual disability. Affected males have breathing problems, with some having episodes in which breathing slows or stops for short periods (apnea). As the child ages, the apnea episodes tend to last longer, especially during sleep, and affected babies often require use of a machine to help regulate their breathing (mechanical ventilation). Most males with MECP2-related severe neonatal encephalopathy do not live past the age of 2 because of respiratory failure.

MECP2-related severe neonatal encephalopathy is the most severe condition in a spectrum of disorders with the same genetic cause. The mildest is PPM-X syndrome, followed by MECP2 duplication syndrome, then Rett syndrome (which exclusively affects females), and finally MECP2-related severe neonatal encephalopathy.

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, or muscle stiffness (rigidity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. About half of individuals have seizures, often of the tonic-clonic type. This type of seizure involves a loss of consciousness, muscle rigidity, and convulsions and may not respond to medication. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately half of individuals learn to walk, and about one-third of people with this condition require assistance when walking. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with only half surviving past age 25.

PPM-X syndrome is a condition characterized by psychotic disorders (most commonly bipolar disorder), a pattern of movement abnormalities known as parkinsonism, and mild to severe intellectual disability with impaired language development. Other symptoms may include muscle stiffness (spasticity), exaggerated reflexes, and an abnormally small head (microcephaly). Affected males may have enlarged testes (macro-orchidism). Not all affected individuals have all these symptoms, but most have intellectual disability. Males with this condition are typically more severely affected than females, who usually have only mild intellectual disability or learning disabilities.