User:Psu2c3/sandbox

Signs and symptoms
The symptoms of Rett syndrome are wide and varied across the lifespan, so different symptoms can present themselves at different times, according to a developmental timeline. The symptoms can encompass those of Autism, Cerebral Palsy, Parkinson’s disease, Anxiety, and Epilepsy.

In Rett Syndrome, girls will show no signs and so will appear normal from birth. Initial development is normal and children will reach all their early developmental milestones. Onset of Rett syndrome occurs between the age of 6 and 18 months. This is known as a period of developmental stagnation where the girl’s development will either slow considerably or stop completely.

This is followed by a period of developmental regression, which occurs between the age of 1-4 years, where language and motor milestones are lost. There is a loss of purposeful hand movements and quite often stereotypical hand movements, like hand washing or wringing, are observed. Due to the loss of language and social skills, girls tend to be extremely anxious and easily distressed in social contexts, which can lead to autism- related behaviours being observed. It is because of this that Rett Syndrome can be misdiagnosed early as autism. Girls often show breathing irregularities such as breath-holding and hyperventilation. It is common during this period for children to experience seizures.

From the age of 3 to 10 years, a stabilisation period will occur, where there will be a reduction in the loss of skills and some may be able to regain some of the skills lost, such as motor and communication skills, so that overall some improvement in their condition may be seen. This is where potential therapies, medications and aids may be implemented to improve their quality of life.

From the age of 10 years and above, a deterioration of motor skills is observed which is consistent to that of Parkinson’s disease and includes: an overall decrease in mobility, scoliosis, dystonia, and muscle rigidity.

In summary, the common symptoms of Rett syndrome are :
 * Avoidance of eye contact
 * Loss of speech
 * Stereotypical hand movements (hand washing/ wringing)
 * Incontinence
 * Screaming fits
 * Breathing irregularities
 * Short stature
 * Motor difficulties
 * Difficulties swallowing
 * Hypotonia
 * Microcephaly (Poor head growth seen in some)
 * Gastrointestinal problems
 * Muscle spasticity
 * Dystonia
 * Bruxism (teeth grinding)
 * Scoliosis

Variants
Congenital variant: (FOXG1 variant)

The FOXG1 gene produces a protein called the ‘forkhead box G1’ protein which is a transcription factor (which helps to regulate the activity of genes) that turns off genes which are no longer needed. This gene has an important role in brain development of the cerebellum, which controls voluntary movement, language and learning. Changes in this gene cause FOXG1 syndrome, a rare disorder, which causes impaired development and structural brain abnormalities. This was previously thought to be a congenital variant of Rett syndrome but now it is considered to be a distinct syndrome.

Symptoms include: microcephaly, low muscle tone, motor difficulties, poor eye contact, stereotypical hand movements, loss of speech.

Zappella variant: (preserved speech variant)

This variant is caused by mutations of the MECP2 gene. Symptoms include: stereotypical hand movements but patients typically recover some degree of speech and hand use. The typical symptoms like scoliosis and epilepsy are rare in this particular variant.

Hanefeld variant: (CDKL5 variant)

The CDKL5 gene produces a protein which is important for typical brain development. It is not known what this proteins function is, but it is believed to regulate the function of the MECP2 gene (gene attributed to Rett syndrome). Children affected by this gene suffer from seizures that begin at only a few months of age. Other symptoms include : scoliosis, motor difficulties, visual impairments, sensory issues and gastrointestinal difficulties, limited speech and lack of eye contact.

Diagnosis
Diagnosis of Rett syndrome usually doesn’t occur for a number of years because symptoms don’t begin to appear until the child is between the age of 6 to 18 months.

Diagnosis will occur mainly based on the child’s symptoms and their meeting the criteria for diagnosing Rett Syndrome, however, confirmation will occur because of an identified MECP2 gene mutation found using a genetic blood test. It is not possible to confirm Rett syndrome simply through genetic testing because mutations of the MECP2 gene can have an influence in other conditions (e.g. MECP2 duplication syndrome and PPM-X syndrome) so as a result a combination of the results from the genetic test and the observable symptoms of Rett syndrome in the child are used to diagnose.