A severe and global developmental disorder affecting
the central nervous system (CNS) characterized by autism, dementia, ataxia, and loss
of purposeful use of the hand. It is known as a uniform and striking progressive
encephalopathy. Evolution in four phases after diagnosis is typical.
Cardiac, respiratory, and gastrointestinal (GI) signs are associated.
RTS; Autism Dementia Ataxia and Loss of Purposeful Hand
First described by Andreas Rett, Austrian pediatrician in
1966; Hagberg in 1983 report 35 patients from France, Portugal, and Sweden.
Only females are affected; incidence estimated at
1:15,000 to 1:20,000 in the general population. However, it has been
suggested that the prevalence is about 1 in 10,000 to 15,000 female newborns
in the United States but most are not reported or misdiagnosed.
Probably X-linked dominant with 100%
antenatal lethality in hemizygous male. All cases should be new mutations
explicable on the basis of gonadal mosaicism or X-autosomal translocation in
Caused by mutation in the gene encoding
methyl-CpG-binding protein-2 (MECP2) located on Xq28. Exact physiopathology
is still unknown, but several reports have shown elevated endorphin levels
in cerebrospinal fluid (CSF) and respiratory pattern is improved with opioid antagonists.
The loss of function of MECP2 protein might intervene at the level of
neurotransmitters and lead to cerebral hypoperfusion.
Clinically evocated. Essential criteria are abnormal
prenatal and perinatal period; an apparently normal psychomotor development
until 6 months of age; a deceleration of head growth (between 5 months and 4
years of age); a loss of acquired purposeful hand skills with development of
severely impaired speech associated with severe psychomotor retardation,
stereotypic hand movements, and gait and truncal apraxia.
Usually normal development until age 1 year followed by regression of language milestones,
with appearance of fine tremor of the hands, ataxic gait, and loss of purposeful movement
of the hands, which may not appear until the girl is 2 to 3 years old. Autistic
behavior becomes evident at this stage. Rupture of head growth becomes evident and is
known as “acquired” microcephalia. The disease is also marked with generalized
tonic-clonic seizures that are well-controlled by antiepileptic drugs, peculiar sighing
respiration, and periods of apnea. There are associated vasomotor disturbances of the
legs. After the initial neurological degradation phase, the disease appears to
plateau (between 6 and 18 months of age) followed by a rapid regression that stays
for a few weeks to a few months. It is followed by stabilization for a few years and,
finally, by a long phase of motor deterioration with loss of ambulation. Clinical features
can also involved heart (prolonged QT interval and T-wave abnormalities), respiratory system (periodic apnea while awake or hyperventilation, breath holding), GI (constipation, gastroesophageal reflux, cachexia), muscles and skeleton
(scoliosis, kyphosis, small feet, vasomotor disturbance with cold feet, muscle
A thorough evaluation of the neurological function
(clinical, EEG, CT/MRI); cardiac function (clinical, ECG); respiratory ...