Rett syndrome

Category: Illness or disabilities

Type

Involuntary

Introduction and description

 

Rett syndrome (RTT), originally termed cerebroatrophic hyperammonemia, is a rare genetic postnatal neurological disorder of the grey matter of the brain that almost exclusively affects females but has also been found in male patients. 

It was first described by Austrian pediatrician Andreas Rett in 1966.

Rett syndrome was formerly classified as a pervasive developmental disorder by the Diagnostic and Statistical Manual of Mental Disorders (DSM), together with the autism spectrum disorders and childhood disintegrative disorder.

Then in 199, Huda Zoghbi demonstrated  that Rett syndrome is caused by mutations in the gene MECP2.  None of this helps the patient of course, it just means that more doctors are fighting over who should treat the person.

Symptoms

 

The clinical features include small hands and feet and a deceleration of the rate of head growth (including microcephaly in some). Repetitive stereotyped hand movements, such as wringing and/or repeatedly putting hands into the mouth, are also noted.

People with Rett syndrome are prone to gastrointestinal disorders and up to 80% have seizures. They typically have no verbal skills, and about 50% of affected individuals do not walk. Scoliosis, growth failure, and constipation are very common and can be problematic.

The signs of this disorder are most easily confused with those of Angelman syndrome, cerebral palsy and autism. Rett syndrome occurs in approximately 1:10,000 live female births in all geographies, and across all races and ethnicities.

Causes

Genetically, Rett syndrome (RTT) is theoretically 'caused' by mutations in the gene MECP2 located on the X chromosome (which is involved in transcriptional silencing and epigenetic regulation of methylated DNA).

But this is not a true cause.  One should be asking - what caused the mutation?

 

To add even more confusion to an already confusing picture, the illness can arise sporadically.  In at least 95% of Rett syndrome cases, the cause is a de novo mutation in the child, that is, it is not inherited from either parent. Parents are generally genotypically normal, without a MECP2 mutation.  In cases of the sporadic form of RTT, the mutated MECP2 is thought to be derived almost exclusively from a de novo mutation on the male copy of the X chromosome. It is not yet known what causes the sperm to mutate.

In less than 10% of RTT cases, mutations in the genes CDKL5 or FOXG1 have also been found to resemble it.  In some very rare cases, no known mutated gene can be found.

So whatever the cause is, it doesn't always result in genetic mutations.

Rett syndrome bears many similarities to so called  inherited or genetic diseases.  In other words, scientists have established that the damage to a gene or genes can result in a set of symptoms, but they have still not worked their way back to establish the true cause - was it nanoparticles, toxins such as pesticides, insecticides, overdosing on fluroride in the water; was it heavy metals such as lead, mercury or cadmium; was it  vaccines or other pharmaceuticals; or was it a virus, bacteria, fungus, bacteriophage or parasite?

For more details please see the description on Inherited and genetic diseases, which discusses these causes in more detail