Imagine two new parents of an adorable little girl. Every day these parents watch their child grow and learn. The young girl begins to crawl and say her first words, like "mama" and "dada". She looks like any other healthy five month old baby. But soon her parents start to notice that their daughter isn't progressing as quickly as she once was. She doesn't try to pull herself up to walk like other children her age and she begins to cry all the time. Finally, her parents visit the doctors and after months and months of testing, their worlds are shattered. Their little girl has Rett Syndrome, a tragic and progressive neurological disorder that is perhaps one of the most heartbreaking and misunderstood disorders.
Rett Syndrome affects approximately 1 in every 10,000 to 15,000 females (National Institute of Neurological Disorders and Stroke [NINDS]). It affects all types of race and ethnicity. Children with this disorder are usually born healthy and show a normal period of growth and development. However, around 6 to 18 months of life, there is a slowing down of skills, followed by a stage of regression where the child loses any communication skills gained and significant use of her hands. Stereotypical characteristics become apparent, with many health problems such as seizures, difficulty swallowing and breathing, and irritability, among countless other symptoms (Hunter 25). First studied by Dr. Rett in Sweden, Rett Syndrome was only first recognized in the United States in 1983, when it was published in a prominent medical journal (D. Harbin). Until then, many girls with this disorder were misdiagnosed with other disorders such as autism, cerebral palsy, or general developmental delay (Hunter 26). Despite the progress made in diagnosing the disorder, unfortunately it is still commonly misdiagnosed today. Rett Syndrome is caused by a mutation in the MECP2 gene on the X chromosome. Scientists and Researchers only indentified this gene in 1999 (NINDS). Because it affects the X chromosome and females have two X chromosomes, the disorder affects almost exclusively females. Few males are also affected, but their symptoms are usually so severe, that they do not survive past age one, if not in utero (D. Harbin). The MECP2 gene has been found to play a significant role in "silencing", or turning off other target genes on the X chromosome. If these genes remain on or active at the wrong time, normal development and nerve cell function can be affected, causing Rett Syndrome. The severity of Rett Syndrome depends on the percent of MECP2 genes that are active. Physiologically, in females that have Rett Syndrome, there is a lack of maturity in the olfactory neurons and the brain is 30% smaller than normal. Because the cell junctions are not well developed, the nerve cells are very close together, when they should be further apart. Different regions of the brain are affected in the following way: Frontal Lobe: necessary for mood and emotion; cerebral blood flow is reduced as it would be in a 7 week old child. Caudate: involved in cognition, awareness, and behavior; much smaller than normal. Cerebellum: needed for equilibrium and balance; reduced cell numbers. Hippocampus: necessary for processing information; thinning. Substantia Nigra: necessary for movement and critical thinking; reduction in the pigment, melanin, and degeneration of cells. Medulla (Brain stem): strong evidence of immaturity, leading to problems with the autonomic nervous system such as sleep, salivation, breathing, heart rate, swallowing, constipation, poor circulation in the extremities, and reduced sensitivity to pain. "Neurotransmitters: reduced numbers; these include 1) Dopamine - necessary for movement and critical thinking, 2) Acetylcholine - necessary for memory, cognition, movement control, and 3) Glutamate - necessary for brain plasticity, important in seizures and cell death" (Hunter 34). As a result of these symptoms, there is immaturity in the atrio-ventricular condition system and there are many gastrointestinal problems that are associated with Rett Syndrome, the most significant being malnutrition. There is progressive weight and height failure unless "aggressive nutritional rehabilitation is begun" (E. Harbin), such as placing a feeding tube in the stomach. Another major problem associated with Rett Syndrome is the occurrence of seizures.
Stages of Rett Syndrome
There are four stages of this disorder. Stage 1 begins around 6 to 18 months of age. The symptoms are just beginning and can be vague, so this stage is often overlooked. In stage 1, there is a slowing of developmental skills. The child may have a "floppy' body due to hypotonia (loss of muscle tone) (NINDS). The baby shows little eye contact and seems disinterested in toys and other objects and she is appears to be calm and quiet. There are other delays in major gross motor developments, especially sitting, crawling, and pulling up to stand. Rate of head growth is slowed and lack of attention can be noticeable. This stage may last only a few months up to a year (Hunter 29).
Stage 2 begins from one to four years of age and can from weeks to months. This is the regression period in which developmental decline is observed. This is often the most tragic stage because the girl will begin to lose most of her acquired skills. She loses the ability to speak and all gross motor skills. This can have a rapid onset or be more gradual, depending on how severe the case is. Stereotypical hand movements develop such as hand-wringing or hand to mouth movements. Breathing irregularities are common, including breath holding, hyperventilation, apnea, and rapid or shallow breathing. There is a major loss of social skills and little interaction can be observed. Girls can exhibit inappropriate laughing and /or crying and have general irritability. Gait is awkward and movements are unsteady, uncoordinated, and jerky. The child has trouble initiating movement, so walking is hard and usually requires assistance with braces. Tooth grinding is also very common.
Stage 3 begins from age two to ten years old. This is a plateau stage, where regression is over and the girl is somewhat stable. This stage can last for many years. Motor problems, scoliosis, and seizures become more prominent. Improvement is seen in behavior and the child is less irritable and once again develops good eye contact and interacts socially. She is more alert than in the previous stages, and attention and communication skills improve. However, she still is unable to speak. Many girls with Rett Syndrome remain in this stage for most of their life.
Stage 4 usually begins after the age of ten. The major characteristic of this stage is reduced mobility. Stage 4-A describes those girls who once could walk, but no longer do so. Stage 4-B describes those girls who could never walk. In this period, muscle weakness and rigidity are prominent features that contribute to an overall loss of movement. Poor circulation causes feet to be swollen, cold, and often bluish in color. There is no further decline in cognitive skills, communication, or hand skills. Puberty begins at a normal age in general, women with Rett Syndrome look younger than they actually are (Hunter 30).
In all four stages, the major debilitating aspect of Rett Syndrome is apraxia, the inability to program the body to perform motor movements (Hunter 26). Everything is impaired, including eye gaze and speech, making communication impossible for most people. Because of this, it is almost impossible to make an accurate assessment of intelligence. These girls are basically trapped inside their minds because traditional testing requires them to use speech and/or hand movements, which is obviously impossible (Hunter 26) However, there are girls who are able to communicate through the use of a computer that follows the user's slightest eye movement. Dr Rett once said, "Of our daughters, they feel all the love given to them. They have a great sensitivity for love. I am sure of this. There are many mysteries, and one of them is the girls' eyes. I tell all the parents to look at their eyes. The eyes are talking to them. I am sure the girls understand everything, but they can do nothing with the information." (International Rett Syndrome Foundation [IRSF])
Treatment & Prognosis
There is no cure of Rett Syndrome yet, but there are various treatments for the symptoms. These include treatments for the orthopedic disabilities, medication for seizures, and nutritional programs and feeding tubes to treat the difficulty of eating and swallowing. Many girls are on several drugs at once and have tried countless others to improve their state of living. Although some drugs work for one girl, they may not on others.
Despite their sever impairments, women with Rett Syndrome have a 70% survival rate at age 35 and live at least into her 40's (E. Harbin). However as the affected get older, the risk of death is increased. The majority of deaths are unexplained and sudden. The major factors associated with unexplained death in Rett Syndrome are uncontrolled seizures, swallowing difficulties, and lack of mobility. Many other deaths of resulted from pneumonia, gastrointestinal infections, and malnutrition. Life expectancy of a person with Rett Syndrome largely depends upon the quality of care she receives as well. The oldest living woman in the United States living with Rett Syndrome is 58 years old (IRSF).
Now that the defective gene has been identified, researchers are currently trying to further clarify the specific location on the gene so that amniocentesis and other genetic testing can be more accurate. Scientists are also working on developing a mouse genome so that they can do testing in laboratories, with hopes towards a cure and improved treatment (D. Harbin).