Discussion:
Rett syndrome-related breathing features, like hyperpnoea followed by breath-holding, Valsalva efforts, and periodic breathing, are easily identifiable during wakefulness. Such symptoms usually reduce or even abruptly disappear at sleep onset[1]. Among the patients with Rett syndrome with pathological polygraph, nearly all present obstructive events during sleep, with a thin minority of central events associated with severe obstructive ones[2]. Remarkably, no patient with RS showed hypoventilation or hypercapnia[2]. MECP2 gene plays an important role in autonomic system regulation [3]. Animal models showed an important role of MECP2 in breathing centres sensitivity to CO2, and its mutations may lead to the typical respiratory instability of RS[4]. To the best of our knowledge, this is the first case reporting hypoxemia and hypoventilation in a patient affected by RS. No articles perform an in-depth analysis of breathing patterns of RS variants, in particular during sleep-time. Patients with CRS are a peculiar cohort; they will never walk autonomously and may acquire the ability to articulate few simple words at best, usually show severe mental retardation since the very first’s months of life. At the diagnosis, only a few cases present epilepsy (the landmark of the classic form), but electrical activity alterations are nearly always identified at the EEG[5], [6].
As previously stressed, the congenital variant is deeply impacted by hypotonia that is as severe as to cause scoliosis within the very first years of life[7]. Therefore, in CRS, hypotony maybe, per se, cause desaturation and hypoventilation as for other neuromuscular diseases in children[8], suggesting different pathogenesis than for classic form of RS. The normality of PtcCO2 during waketime (when muscle strength is relatively increased) supports this suggestion. Of particular interest is the persistent periodic breathing of this patient. Breathing centres homeostasis is very fragile in RS due to MECP2mutation[4], with a consequent high gain loop causing periodic breathing. Such events may be boosted by repeated desaturations caused by CRS-related hypotonia[9], [10]. Therefore, although a ST mode of ventilation is usually preferred to maximize patient comfort, an assisted pressure-controlled mode could be necessary to overcome the lack of appropriate respiratory centres control. Providing an adequate ventilation in such patients could contribute to the daytime quality of life and hypotonia improvement, as already reported for other hypotonic diseases[8].
In conclusion, we think that this single case suggests the need for a very early polygraph or at least pulse oximetry plus capnography in each patient affected by the congenital variant of Rett syndrome. Broadly speaking, we suggest considering a diagnosis of congenital Rett syndrome patients with hypotonia without a diagnosis.
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