| Respiratory |
| Alveolar hypoventilation, with increased PCO2 and hypoxemia. Low tidal volume and/or respiratory rate. |
| Lack of normal ventilatory and arousal responses to hypercarbia and hypoxemia |
| Limited breath-to-breath variability |
| Cardiac |
| Decreased beat-to-beat variability of heart rate |
| Attenuated heart rate response to exercise |
| Orthostatic hypotension |
| Attenuation of normal sleep-related blood pressure decrement |
| Prolonged sinus pauses |
| Facial features |
| Box-shaped face (shorter and flatter), with inferior reflection of the lateral segment of the vermillion border on the upper lip |
| Gastrointestinal |
| Hirschsprung disease (16 to 20%) |
| Severe constipation |
| Esophageal dysmotility; dysphagia |
| Neural crest tumors |
| eg, neuroblastoma, ganglioneuroblastoma, or ganglioneuroma |
| Ophthalmologic |
| Pupillary abnormalities (meiosis; altered pupillary response to light) |
| Altered accommodation (with accommodative strabismus) |
| Neuropsychological |
| Decreased perception of anxiety |
| Cognitive delays |
| Sudomotor |
| Sporadic profuse sweating |
| Decreased basal body temperature |
