Rett Syndrome (RTT)
Rett Syndrome (RTT) is a genetic disease which presents with a seemingly normal development up until 1-3 years of age.
The disease is only present in females, as it is an X-linked dominant disorder and males with a defective X chromosome die prematurely. It is rare, with an estimate of 1:10000 - 1:15000 live female births. (4)
This is when Stage II begins, with deterioration of mental processes. The rate of deterioration varies. Symptoms include babble or loss of speech, unable to use hands properly, no wanting to socialize, not sleeping well and poor head growth. (1)
Stage III is when the deterioration reaches a plateau, with the landmarks of the disease present. These include: stereotyped …show more content…
Mutations in the gene coding for Cyclin-Dependent Kinase-Like 5 (CDKL5) present like early-seizure onset Rett 's and cause severe mental retardation. They can show features similar to Rett Syndrome even lacking the MECP2 mutation. (8) Patients with mutations in the FOXG1 gene can present with the congenital variant of Rett’s. The gene codes for a protein which may share common roles with MECP2 in brain development. (9)
Diagnosis of Rett’s is clinical, not genetic. The main criteria, the key component of diagnosis of Rett’s include: loss of hand skills, spoken language, and normal gait, plus stereotyped hand movements. See Fig 1 for details.
There is a diagnostic test available for Rett’s Syndrome which finds the mutation for up to 95% of females with typical Rett’s. A combination of sequencing via PCR (finds 80-85% cases) and deletion analysis (adds another 10%) is used for the test. This gives a very sensitive test.
The test can be requested when a clinician or parent wants it.Since symptoms of Rett’s are highly varied, doctors often have a hard time knowing when to refer a patient to be tested.
The test is expensive and time consuming and there is no specific screening test. The expense of the test, the lack of an effective treatment and low incidence of Rett’s provides disincentive for the test to be widely …show more content…
Also, since most cases are from a spontaneous mutation, there is no carrier testing.
The effect of genotype on phenotype has been studied. Mobility, self-care, upper and lower extremity use (phenotypes) varies among the different mutations of MECP2 (genotypes). The significance of this is to try earlier intervention for patients with higher risk mutations, and for a more accurate prognosis. See Fig 2 for the results table. (2)
To summarize the differences, R133C was the least affected overall by symptoms. For mobility, T158M patients were most affected and R133C the least. For self-care and upper extremity use, patients with large deletions, R255X and R168X were most affected. Those who had uncommon mutations or R133C were least affected. There was also some differences depending on if the mutation was missense or truncating. For example, truncation mutation patients tended to have progressed onto Stage IV earlier, had higher rates of microcephaly, and exhibited different types of tremor. (2)
As of now there is no cure for Rett’s. Patient’s are managed symptomatically such as with sleep aids, social medications, physical therapy