Rett's disorder Health Article

Definition

Rett's disorder, which is also known as Rett's syndrome or RS, belongs to a group of childhood disorders known as pervasive developmental disorders(PDDs) or autistic spectrum disorders. It is classified by the mental health professional's handbook (the Diagnostic and Statistical Manual of Mental Disordersor the DSM-IV-TR) as a developmental disorder of childhood. Rett's disorder is characterized by an early-onset slowing of the infant's head growth and a reduction in brainsize, as much as 30%.

Description

RS was first described by an Austrian physician, Andreas Rett, in 1966; prior to 1983, however, little was known about the syndrome because its occurrence is quite rare. Although RS was thought at first to result from the destruction or degeneration of brain tissue, genetic research has indicated that it is caused by the failure of the infant's brain to develop normally. This developmental failure is in turn caused by a genetic mutation affecting production of a key protein that regulates brain development.

Rett's disorder has a distinctive onset and course. The child— almost always a girl— develops normally during the first five months of life. After the fifth month, head growth slows down and the child loses whatever purposeful hand movements she had developed during her first five months. After 30 months, the child frequently develops repetitive hand-washing or hand-wringing gestures; 50%–80% of children with the disorder will eventually develop epilepsy. Rett's disorder is also associated with severe or profound mental retardation.

Causes

The cause of Rett's disorder is a genetic mutation on the long arm of the X chromosome (Xq28) at a locus known as MECP2. The gene was discovered in 1999, and it produces a protein known as MeCP2, which is essential to life and crucial to the normal development of the human brain. The mutation that causes Rett's disorder allows other genes to become or remain active at inappropriate points in the brain's development. These activated genes interfere with the normal pattern of development and maturation of the brain's functions. Although Rett's disorder was previously thought to result from degeneration or deterioration of brain tissue, the discovery of the Rett's gene provides evidence that the disorder may be due to a failure of normal brain development. The sensory, motor, and emotional functions of the brain are not integrated in Rett's patients as they are in persons without the mutation. Certain regions of the brain in Rett's patients essentially remain at an infantile stage of development.

RS is classified by geneticists as an X-linked dominant disorder with a high rate of new mutations. Most of these mutations (99.5%) occur while the fetus is developing in the mother's womb; only 0.5% of cases of Rett's disorder are recurrences within families. One of the most important aspects of the discovery of the Rett gene is that RS is the first disorder in humans to be traced to defects in a protein (MeCP2) that controls the expression of other genes through its interaction with methylated DNA. The discovery uncovered a new class of genetic disease that might extend far beyond RS in its applications to other disorders related to developmental failures of the nervous system.