5-HTT polymorphisms in congenital central hypoventilation syndrome contribute to a modified resting CO2 set point
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Background . Central respiratory chemoreceptors are not definitively identified, but the retrotrapezoid nucleus is the main center whose absence is characteristic of congenital central hypoventilation syndrome (CCHS). Intense chemosensory stimuli activate circuits that are wake- or attention-promoting, such as the raphe, which modulates chemoreflexes. The main objective of our study was to assess whether residual central CO 2 chemosensitivity in CCHS is related to serotonin transporter gene polymorphisms (homozygous long (ll) variant versus variants with short form, ss or sl). Twenty-three children with CCHS and PHOX2B pathogenic variants had peripheral (controller gain measurement) and central CO 2 chemosensitivity assessment (hyperoxic, hypercapnic test), resting end-tidal PCO 2 (PETCO 2 ) measurement and 5-HTT polymorphism determination. Results . The percentages of the ll, ls, and ss genotypes were 5/23 (22%), 14/23 (61%) and 4/23 (17%), respectively, and were not influenced by Phox2b mutations. Both central (0.16 L/min/mmHg [0.02; 0.33] versus 0.21 [0.06; 0.41], P=0.551) and peripheral (0.47 L/min/mmHg [0.026; 0.71] versus 0.67 [0.24; 1.26], P=0.602) CO 2 chemosensitivities were not significantly different when comparing the L group (n=5) and the S group (n=18), while their resting PETCO 2 values were different; the L group presented a higher PETCO 2 value than the S group did (49.3 mmHg [46.9; 53.0] versus 42.0 [36.7; 44.8], P=0.014). Conclusions . The CO 2 chemosensitivity of children with CCHS was not related to 5-HTT transporter polymorphisms, whereas the ll homozygous variant contributed to resting alveolar hypoventilation.
