Ross syndrome: a case series of five patients

INTRODUCTION

Ross syndrome, initially described by Ross in 1958, is a rare peripheral autonomic nervous system disorder.¹ The condition is marked by three main features: segmental hypohidrosis or anhidrosis, areflexia, and Holmes-Adie’s tonic pupil. Harlequin syndrome represents the first two component of this triad, while Holmes-Adie syndrome includes the latter two features, posing challenges in differentiation from Ross syndrome due to their shared pathogenesis.² Etiological factors include autoimmunity, viral infections, genetic factors, autonomic denervation, and nuclear synuclein deposition. The exact cause of selective cholinergic denervation remains under research.

Approximately 60 cases worldwide exhibit the classical triad of symptoms and signs.³ Here, we report five cases with clinical and histological features of Ross syndrome.

CASE SERIES

Case 1

A middle-aged female homemaker presented with an absence of sweating on the left side of the body with increased heat tolerance and left-sided headache for 1 year. She also had increased sweating over the right side. Past- history revealed multiple episodes of seizures in 2017. There was no history of palpitations, orthostatic hypotension, syncope, urinary or bowel complaints or trauma to the spine. Clinical examination revealed anhidrosis on the left side with hyperhidrosis on the right side predominantly involving C3-7 and T6-10 dermatomes. Starch iodine test reflected the clinical findings (Figure 1 A-C).

Deep tendon reflexes were absent. Ophthalmological examination revealed mid-dilated left pupil with the absent pupillary light reaction but reacting better to accommodation was noted suggesting a tonic pupil with light-near dissociation.

Case 2

A middle-aged male construction worker presented with an absence of sweating on the right side of the body with increased heat tolerance for 10 years. He also had increased sweating over the left side (Figure 2 A and B).

Case 3

A middle-aged female homemaker presented with an absence of sweating on the left side of the body with increased heat tolerance and increased sweating over the right side for six years (Figure 3 A-D). There was history of palpitations, tingling and numbness, easy fatiguability, epigastric pain and discomfort. The patient had been on beta-blockers for the past three years.

Case 4

A middle-aged female homemaker presented with an absence of sweating on the right side of the body with increased heat tolerance and increased sweating over the left side for two years (Figure 4 A-C).

Case 5

A young male student presented with an absence of sweating on the right side of the body with increased heat tolerance for three years. He also had increased sweating over the left side (Figure 5A and B).

In all five patients, there was no history of spine trauma, family history was insignificant, blood pressure was normal in both supine and standing positions, sensory examination was normal, and peripheral nerves were not thickened.

Histopathology was done in all the patients which has been mentioned in Figure 6, 7 and Table 1.

Based on the findings mentioned above and in Table 1, Ross syndrome was diagnosed in all five patients. They were advised to avoid heat exposure and to wear damp clothing during household chores or other physical activities to prevent episodic hyperthermia.

DISCUSSION

Ross syndrome is a rare disorder of the peripheral autonomic system, characterized by segmental hypohidrosis/anhidrosis, areflexia, and Holmes-Adie’s tonic pupil. In our case series of five patients, two had the complete triad, while three had incomplete forms with varying combinations of symptoms.

The condition results from primary impairment of postganglionic sudomotor and pupillary fibers, affecting both genders and typically presenting between ages 3 and 50. The tonic pupil and decreased sweating are linked to dysfunction of cholinergic fibres innervating the iris and sweat glands.⁴ Extensive anhidrosis can trigger compensatory hyperhidrosis, which may be severe and require treatment. This could be due to compensatory mechanisms or early loss of presynaptic M2 cholinergic receptors.⁵

Differential diagnoses include Shy-Drager disease, multiple sclerosis, diabetes, leprosy, and polyneuropathies.⁶ Hyporeflexia arises from involvement of neurons in the dorsal root ganglia and spinal interneurons and may be accompanied by other autonomic dysfunctions, including orthostatic hypotension and cardiac dysautonomia.^7,8

No specific treatment exists for Ross syndrome, and management focuses on symptom control. Hyperhidrosis can be treated with botulinum toxin, iontophoresis, or anticholinergics, while hypohidrosis is managed by avoiding hot environments and damp clothing.^9,10

CONCLUSION

Ross syndrome is a rare disorder of peripheral nervous system characterized by segmental hypohidrosis/ anhidrosis, areflexia, and Holmes-Adie’s tonic pupil. In our case series of five patients, a diagnosis of 'complete' Ross syndrome was made for two patients, while the remaining patients were diagnosed with 'incomplete' Ross syndrome. Although Ross syndrome is benign, it can significantly impact social interactions, making proper patient counselling essential. The discovery of five cases from a single centre suggests that Ross syndrome may be more common than previously reported in the literature.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

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