Introduction

Rett syndrome (RTT) is a unique X-linked dominant neurodevelopmental disorder that affects 1 in 10,000 females. Six cardinal features evolve due to immaturity of the brain in RTT.

Two cortical features include severe mental retardation and epilepsy. The third feature is extra-pyramidal with dystonia, orthopaedic deformations of which scoliosis is the most common, secondary muscle wasting, incoordination of actions.

The fourth is monoaminergic dysfunction in the brainstem with dyspraxia, sleep disturbance, frequent daytime sleeping, night awakening and agitation.

The fifth feature may be due to incompetence of the neuronal network of inhibitions in the brainstem secondary to immaturity with abnormal breathing rhythms in the awake-state (3). These resulting abnormal breathing rhythms and accompanying autonomic dysfunctions can explain the sudden deaths accounting for at least 25% of all deaths in RTT. Irregular breathing in RTT as a consequence of immature brainstem function has been described in detail elsewhere.

The sixth feature recognised as part of brainstem dysfunction in RTT is dysautonomia. In addition to previously known autonomic features like delayed nociception and cold, blue extremities, there is a unique sympatho-vagal imbalance in which the sympathetic tone is normal but the parasympathetic tone is very low and remains at the neonatal level throughout life.