Rett syndrome is a disorder seen in female children characterized by the loss of verbal abilities and cognition, and the development of ataxia and stereotyped hand-.
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A 4-year-old girl comes to the office because she has stopped talking suddenly. She had a roughly 20-word vocabulary at her last visit, one month ago, but has not talked in two days. Her parents say she has become less socially engaged since the last visit, but they thought she was just shy. Physical examination shows an unsteady gait and throughout the exam she sat quietly in the corner, wringing her hands together. She has bruises on her knees, which her parents say happened after falls. Which of the following is the most likely diagnosis?
A classic feature is that children often make repetitive hand movements - like flapping their hands or clasping their hands together tightly.
The disease was named after Dr. Andreas Rett, a pediatrician who discovered the syndrome in the 1960s.
To begin, the brain is composed of billions of interconnected neurons, each of which is made of up dendrites, that receive signals from other neurons, the soma, or cell body, which has all of the neuron’s main organelles, and the axon which sends signals to other neurons.
In Rett syndrome there’s an X-linked autosomal dominant mutation of the Methyl-CpG-binding protein 2 gene, or MECP2 gene, which codes for MeCP2 protein.
The mutation in the MECP2 gene usually occurs sporadically, meaning that it’s usually not inherited from a parent.
It’s thought that the MeCP2 protein helps to silence or turn off other genes.
Males have only one X chromosome, so if there’s a mutation in the MECP2 gene, then they cannot make functional MeCP2 protein, and that might be why males with the mutation typically die in utero or shortly after birth.
Females have 2 X chromosomes, however, so one mutated MECP2 gene can be compensated for by a normal MeCP2 gene on the other X chromosome.
The genes that are regulated by MeCP2 proteins are particularly important for brain development, specifically to help establish neuronal connections.
So in young girls, when they’re first born, the low levels of MeCP2 proteins are sufficient for normal brain development. But as the brain grows more complex, the level of MeCP2 becomes insufficient and the brain fails to develop normally.
In addition to neurologic effects, Rett syndrome is also associated with prolonged QT syndrome, which is when it takes longer than usual for the heart to repolarize.
Rett syndrome can be thought of in four main stages.
The first stage is the early onset stage and occurs between ages 6 to 18 months.
Before 6 months of age, children with Rett syndrome develop normally, but starting around 6 months, children start to lose interest in play and no longer maintain eye contact.
The second stage is the rapid deterioration stage and occurs between ages 1 to 4 years. In this stage there is a dramatic regressions in speech and motor skills.