Reliability of Composite Autonomic Symptom Score (COMPASS)-31 in Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by alveolar hypoventilation and variable autonomic nervous system (ANS) dysfunction (ANSD) due to mutations in PHOX2B, a gene crucial for ANS neural crest lineage differentiation.

Objectives and methods: Our prospective study aims were twofold: to (1) assess the relationships between the subjective Composite Autonomic Symptom Score (COMPASS)-31 and objective indices of ANSD obtained from heart rate variability analyses, ambulatory blood pressure (BP) monitoring, and CO₂ chemosensitivities and (2) describe the organ system ANSD, its relationship to PHOX2B genotype, and its consequences on quality of life (PedsQL) in children with CCHS.

Results: Thirty-two PHOX2B mutation-confirmed subjects (median [range] age 9.2 years (4.4; 18.0), 15 girls) were enrolled. COMPASS-31 was assessed in 32 matched (sex and age, range: 4.3; 18.9 years) healthy controls. As compared to healthy controls, children with CCHS had increased vasomotor (p = 0.001), secretomotor (p = 0.021), gastrointestinal (p = 0.002) and pupillomotor (p = 0.028) scores and decreased orthostatic intolerance scores (p = 0.050). There was no difference in overall COMPASS-31 score between CCHS and controls (p = 0.083). However, in CCHS, overall COMPASS-31 scores correlated with high frequencies (HF) normalized (cardiac parasympathetic modulation: R = -0.53; p = 0.002), low frequencies (LF)/HF ratio (R = 0.56; p< 0.001), and both systolic and diastolic nighttime BP dipping (R = 0.45, p = 0.012 and R = 0.40, p = 0.028, respectively). No significant relationships between COMPASS-31 scores and chemosensitivity testing, PedsQL scores, or PHOX2B genotype were identified.

Conclusions: COMPASS-31 identified some aspects of CCHS-related ANSD, and scores correlate with objective ANS function measures, supporting the potential utility of COMPASS-31 in CCHS.