Rett Syndrome

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 Use Syndrome.

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 the mother.

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 wasting).

A thorough evaluation of the neurological function (clinical, EEG, CT/MRI); cardiac function (clinical, ECG); respiratory function because of scoliosis and breathing dysfunction (clinical, chest radiographs, pulmonary function test if possible, and arterial blood gas analysis); and gastroesophageal reflux (clinical, endoscopy, manometry) is essential. Preoperative laboratory investigations should include electrolytes because of prolonged QT interval.

Careful intraoperative positioning is needed. A rapid sequence induction is recommended considering the increased risk of pulmonary aspiration because of gastroesophageal reflux. Delayed recovery is common after anesthesia. Postoperative intensive care admission is advised because of poor respiratory control. The need for mechanical ventilation is highly probable. Postoperative analgesia must take into account the already elevated endorphin levels and poor respiratory control. A case report of sudden death occurring 4 weeks after anesthesia is reported. Loco-regional anesthesia techniques have not been reported, but should be considered given the respiratory system involvement and the reduction in opioid use. However, patient compliance is most likely poor and sedation will be required.

Continue antiepileptic medication up to the operation and resume them afterwards as soon as possible. In case of prolonged surgical procedure, the administration of intraoperative Dilantin or phenobarbital must be considered to avoid undetected seizure activities. Consider the interaction between antiepileptic and anesthetic drugs. Avoid sedatives in the preoperative period since these patients may be very sensitive to their respiratory depressive effect. Careful titration of opioids is recommended. No problems have been reported with neuromuscular blocking agents.