Case Report of a Child with Harlequin Syndrome and Nance-Horan Syndrome

Case Report

Austin J Clin Ophthalmol. 2024; 11(1): 1174.

Case Report of a Child with Harlequin Syndrome and Nance-Horan Syndrome

Breen HA¹; McLoone E¹; Jackson AJ²*

¹Department of Ophthalmology, Royal Victoria Hospital, Belfast, UK

²Northern Ireland Clinical Research Network, Belfast Health and Social Care Trust, UK

*Corresponding author: Jackson AJ Ophthalmology Department, Royal Victoria Hospital, 274 Grosvenor Road, Belfast, BT12 6BA, United Kingdom. Tel: 03005550114 Email: Jonathan.jackson@belfasttrust.hscni.net

Received: December 06, 2023 Accepted: January 19, 2024 Published: January 26, 2024

Abstract

We present the case of a child with idiopathic Harlequin Syndrome and X linked recessive Nance Horan Syndrome, the first case that we are aware of with both rare syndromes occurring simultaneously.

Nance Horan Syndrome causes congenital cataract and variable intellectual disability with facial and dental anomalies. Harlequin Syndrome is characterized by hemifacial flushing due to contralateral loss of sympathetic innervation to the skin.

The co-presentation of these two conditions posed a diagnostic challenge due to iatrogenic post-lensectomy pupillary changes.

Keywords: Nance Horan Syndrome; Harlequin Syndrome; Facial flushing; Congenital cataract; Iatrogenic miosis; c.4449C>G p.(Tyr1483Ter)

Abbreviations: NHS: Nance Horan Syndrome; T2-T3: thoracic vertebral level 2-3; CCFDN: Congenital cataracts, Facial Dysmorphism and Neuropathy; HCC: Hypomyelination and Congenital Cataracts

Introduction

Harlequin Syndrome is a rare condition caused by unilateral autonomic dysregulation affecting the face and sometimes the arms and trunk [1,2]. Patients demonstrate episodic, often striking, hemifacial flushing and diaphoresis with an abrupt demarcation at the midline. It is usually precipitated by exercise, heat or emotion but has also been observed during the sleep/wake cycle in infancy [3]. The skin on the affected side is unable to flush or perspire due to lack of autonomic vasomotor and sudomotor innervation [1-3]. The contralateral skin experiences compensatory sympathetic hyperstimulation resulting in excessive flushing and perspiration [1].

Harlequin Syndrome can be idiopathic or secondary [2,4]. Secondary Harlequin Syndrome can be caused by lesions of the sympathetic pathway that run from the hypothalamus to the lateral horn of the spinal cord, travel via T2-T3 nerve roots to the sympathetic chain and extend onto the internal and external carotid arteries via the superior cervical ganglion [1-3]. Thus traumatic, compressive, inflammatory, ischemic or iatrogenic insults at any part of this sympathetic pathway can result in Harlequin syndrome with or without other dysautonomic syndromes such as Horner’s, Holmes-Adie and Ross syndromes. [2-7].

Nance-Horan Syndrome (NHS) is a rare X-linked recessive disorder characterized by congenital cataract, dysmorphic facies and dental anomalies [8-10]. Microcornea, microphthalmia, strabismus, nystagmus and moderate intellectual disability are also associated [8, 9]. As it is X-linked, it tends to present with a more severe phenotype in affected males. Female heterozygotes are variably affected and can be asymptomatic. They display a classic lens opacity of variable severity centered on the posterior Y-suture [11].

Case Report

We present the case of a young girl with both Harlequin Syndrome and symptomatic Nance-Horan Syndrome. The authors are not aware of another documented case of these two syndromes simultaneously affecting one patient.

Our patient presented to the Royal Victoria Hospital Pediatric Ophthalmology Department in Belfast, United Kingdom, as an infant in 2018 for screening due to a maternal family history of congenital cataract.

She had a visually significant lens opacity in her left eye and a mild cataract in her right eye. She does not exhibit any other features of NHS.

She underwent left lensectomy at two months of age with subsequent aphakic contact lens correction. She required occlusion therapy following left lensectomy to stimulate left visual development. At six months old she was noted to have a small left esotropia and manifest nystagmus. At two and a half she developed a small right esotropia that was felt to be related to deterioration of right vision due to progression of her right cataract. She required right lensectomy with aphakic spectacle correction at the age of two years and ten months.

After her primary lensectomy in 2018 genetic testing identified a mutation in the NHS gene described as c.4449C>G p.(Tyr1483Ter). At that time the mutation was not known to be pathogenic. This mutation has since been identified in another family with NHS and upgraded to “likely pathogenic”. NHS was therefore felt to be the underlying unifying cause of her and her mother’s congenital cataracts.

At eighteen months old, fourteen months after her left lensectomy and sixteen months prior to her right lensectomy, her mother observed two episodes of hemifacial flushing involving her left brow, cheek and upper lip. These lasted for a few hours and spontaneously resolved. The patient was not demonstrably upset or overheated but we can speculate that she may have been undertaking exercise as part of her usual daily activities at the time of onset. The patient was otherwise well with no systemic or neurological symptoms (Figure 1).

Citation: Breen HA, McLoone E, Jackson AJ. Case Report of a Child with Harlequin Syndrome and Nance-Horan Syndrome. Austin J Clin Ophthalmol. 2024; 11(1): 1174.