Clinical presentation and autonomic profile in Ross syndrome

Background: Ross syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and segmental anhidrosis. We sought to characterize the clinical presentation, associated autoimmune disorders, and autonomic profile in patients with Ross syndrome to further elucidate its pathophysiology. Methods: We performed a retrospective chart review of all patients who underwent a thermoregulatory sweat test (TST) between 1998 and 2020 and had confirmation of the diagnosis of Ross syndrome by an autonomic disorders specialist. Standardized autonomic reflex testing was reviewed when available. Results: Twenty-six patients with Ross syndrome were identified. The most common initial reported manifestation was an abnormal segmental sweating response in 16 patients (described as hyperhidrosis in 12 patients and anhidrosis in 4 patients) while a tonic pupil was the initial manifestation in 10 patients. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency. An associated autoimmune disorder was identified in one patient. Positive autoantibodies were found in a minority of patients often with unclear clinical significance. Distributions of anhidrosis encountered were segmental (n = 15), widespread (n = 7), and global (n = 4). Well-circumscribed small areas of preserved sweating within areas of anhidrosis were observed in the majority of patients (88.5%). Anhidrosis progressed slowly over time and sudomotor dysfunction was predominantly (post)ganglionic. Cardiovagal and adrenergic functions were preserved in most patients. Conclusions: The pattern of autonomic dysfunction in Ross syndrome is suggestive of a limited autonomic ganglioneuropathy. Sudomotor impairment is prominent and should be the focus of symptomatic management; however, clinicians should be aware of symptoms beyond the classic triad.