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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