RETT SYNDROME

I. Definition

- Rett syndrome (specifically known as

Classic Rett syndrome) is a unique
postnatal neurological disorder that is -
first recognized in infancy and seen
almost always in girls, but can be rarely
seen in boys.

o Atypical Rett syndrome is a
neurodevelopmental disorder
that is diagnosed when a child
has some of the symptoms of Rett syndrome
but does not meet all the diagnostic criteria. 
o In males, this condition is described as MECP2-related severe neonatal
encephalopathy. The signs and symptoms in some males with an MECP2 gene
mutation are on the milder end of the spectrum.

- Rett syndrome strikes all racial and ethnic groups, and occurs worldwide in 1 of every
10,000 female births. Every day, about 20 girls are born with Rett syndrome.
Approximately, more than 6500 girls are born with this disease every year.

- It has been most often misdiagnosed as autism, cerebral palsy, or non-specific

developmental delay.

- The disease was named after Dr. Andreas Rett, an Australian physician who made the
first article on the said disease in 1966 but it was not recognized until the second
article that was written by Dr. Bengt Hagberg in 1983.

- Studies have determined that a girl with Rett syndrome has a 100% chance of reaching
age 10, a 90% chance of reaching age 20, a greater than 75% chance of reaching age
30, a  greater than 65% chance of reaching age 40, and a greater than 50% chance of
reaching age 50. In short many people who have Rett syndrome can live into
middle age and possibly beyond but with assistance throughout their lives.

II. Signs and symptoms

 III. Stages

1. Early onset
- This stage is sometimes unnoticeable. It starts between 6-18 months of age where the
affected child start to lose interest in toys or lack eye contact.
2. Rapid destructive stage
- Stage two starts between 1-4 years of age. They lose the ability to speak, slowed brain
and head growth (microcephaly) is evident and have repetitive hand movements
(wringing, washing, tapping). They also tend to put hands to the mouth often and have
difficulty to move on their own. Some cry, scream and become very irritable.

3. Plateau or Pseudo-stationary stage

- Stage three starts between 2-10 years of age. Apraxia (the inability to perform
purposive tasks or movements when asked as a result of brain damage), seizures and
motor problems occur during this stage. There is less crying and less irritability.
Improvement of hand and eye contact increases. Many girls remain in this stage for
the rest of their lives.

4. Late motor deterioration stage

- Slowing of developmental regression, joint deformities, reduced mobility, muscle
weakness, movement disorders and scoliosis develop in the last stage. Bruxism or the
grinding of teeth and repetitive movement or dystonia may also occur. Sudden death
can happen and is often caused by seizure, aspiration pneumonia, malnutrition, and
accidents.

IV. Causes

V. Inheritance

- In more than 99 percent of people

with Rett syndrome, there is no history
of the disorder in their family. Many of
these cases result from new mutations
in the MECP2 gene.

- Researchers determine that classic Rett

syndrome and variants caused
by MECP2 gene mutations have an X-
 linked dominant pattern of inheritance. A condition is considered X-linked if the
mutated gene that causes the disorder is located on the X chromosome, one of the
two sex chromosomes. The inheritance is dominant if one copy of the altered gene in
each cell is sufficient to cause the condition.

*Comparison of the normal female karyotype (left)

and the karyotype of female with Rett syndrome (right)
VI. Complications

VII. Diagnosis

 Blood Test

Genetic evaluation of a blood sample can identify whether a child has one of the known mutations
that cause Rett syndrome. Even if a child has a mutation of the Methylcytosine-binding protein 2
(MECP2) gene (which also occurs in other conditions), the symptoms of Rett syndrome may not
always be present, so health care providers also need to evaluate the child's symptoms to confirm
a diagnosis.

 Genetic Testing

Trough gene testing, mutations in another gene on the X-chromosome known as CDKL5 (cyclin-
dependent kinase-like 5) can cause an atypical form of Rett syndrome and generally test negative
for a MECP2 mutation. 

Main Diagnostic Criteria

 A pattern of development, regression, then recovery or stabilization
 Partial or complete loss of purposeful hand skills such as grasping with fingers, reaching
for things, or touching things on purpose
 Partial or complete loss of spoken language
 Repetitive hand movements, such as wringing the hands, washing, squeezing, clapping, or
rubbing
 Gait abnormalities, including walking on toes or with an unsteady, wide-based, stiff-legged
gait

VIII. Treatment/management
References

https://www.rettsyndrome.org/document.doc?id=168

https://www.gillettechildrens.org/conditions-care/rett-syndrome

https://www.rettsyndrome.org/about-rett-syndrome

https://ghr.nlm.nih.gov/condition/rett-syndrome

https://www.nichd.nih.gov/health/topics/rett/conditioninfo/diagnosed

https://www.mayoclinic.org/diseases-conditions/rett-syndrome/symptoms-causes/syc-20377227

http://www.rettuk.org/what-is-rett-syndrome/diagnosis/