Abstract
Purpose
This report describes pseudopapilledema in two siblings with Cockayne syndrome and examines a structural mechanism for its development.
Observations
Two siblings with genetically documented Cockayne syndrome, enophthalmos, and hyperopia were found to have pseudopapilledema. Magnetic resonance (MR) imaging disclosed retrodisplacement of the globes, axial foreshortening, posterior scleral flattening, and protrusion of the optic papilla into the vitreous.
Conclusions and importance
In the setting of Cockayne syndrome, pseudopapilledema may arise from retrodisplacement of the globes causing indentation of the posterior sclera by the distal optic nerves. This anatomic aberration may contribute to the development of hyperopia as well.
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Introduction
Cockayne syndrome is a rare autosomal recessive neurodegenerative disorder that is associated with multiple systemic derangements. Ophthalmologic findings include severe enophthalmos, high hyperopia, cataracts, photophobia, corneal epithelial degeneration, poor pupillary dilation, and a progressive retinal dystrophy. , The progressive enophthalmos is classically attributed to loss of orbital fat. We present two siblings with genetically confirmed Cockayne syndrome in whom pseudopapilledema may have arisen from severe enophthalmos with mechanical compression of the posterior sclera by the distal optic nerves.
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Case series
Case 1: A 3-year-old boy presented for evaluation of global developmental delay, nystagmus and poor growth. He was born at 38 + 5 weeks gestation following a pregnancy complicated by intrauterine growth retardation. His growth parameters in the nursery were at the 3rd percentile. Developmental Pediatrics was consulted prior to age 2 years due to global developmental delay and hypotonia. He was assessed by Endocrinology for his growth at 3 years of age due to the height and weight being below the 3rd percentile and was noted to have an advanced bone age 5 years. His endocrine and Gastroenterology evaluations did not determine a specific cause for his poor growth. The alanine aminotransferase was elevated at 86 U/L (normal 7–55 U/L).
Six months later, he had continued to gain skills with the majority of his skills falling in the 18–24 month range. His head circumference was below the 3rd percentile. He had thin blonde hair with decreased subcutaneous tissue in the face. Enamel dysplasia with dental caries were present. Ophthalmologic examination disclosed brisk optokinetic responses, normal pupillary responses to light, no strabismus or nystagmus, severe enophthalmos ( Fig. 1 ), hyperopia (+4.25 + 1.50 × 103 OD, +5.25 + 1.00 × 93 OS), and bilateral pseudopapilledema ( Fig. 2 ). There were no cataracts or retinal pigmentary abnormalities. His neurological examination was significant for normal tone with tightness at the ankles bilaterally and diffusely decreased deep tendon reflexes.
Magnetic resonance (MR) imaging of the brain demonstrated lack of myelination of the cerebral white matter with normal myelination of the brainstem, cerebellum, corpus callosum, optic radiations and deep cerebral white matter, with thinning of the corpus callosum. Minor mineralization was noted within the deep frontal and parietal white matter. Orbital MR imaging showed retrodisplacement and axial foreshortening of the globes with posterior scleral flattening and protrusion of the optic papilla into the vitreous ( Fig. 2 ). There was no compression of the pituitary gland within the sella (i.e. no empty sella). Lumbar puncture under general anesthesia revealed a normal opening pressure 22.5 cm H 2 O. Based on his neuroimaging findings and clinical presentation, molecular testing for Cockayne syndrome was performed which revealed 2 pathogenic variants in ERCC6 . His father carried the pathogenic variant c.466 C>T; p.Q156X and his mother carried the pathogenic variant c.1040delG; p.G347DfsX13.
Case 2: His 18-month-old sister was evaluated due to poor growth and mildly delayed gross motor skills. Her examination was significant for diffusely decreased deep tendon reflexes and mild gross motor delay with normal tone. Her history was significant for lack of ability to smell. The ALT was elevated at 84 U/L. Ophthalmological examination showed almost identical findings to the brother, with a greater degree of enophthalmos ( Fig. 1 ), hyperopia (+3.50 + 0.75 × 103 OD, + 4.50 + 1.00 × 092 OS), and bilateral pseudopapilledema ( Fig. 3 ). MR imaging of the brain revealed widespread hypomyelination/dysmyelination ( Fig. 3 ), with apparent absence olfactory bulbs and tracks bilaterally. Orbital MR imaging showed a similar retrodisplacement and axial foreshortening of the globes, and protrusion of the optic papilla (arrows) into the vitreous to that seen in her brother, however, she had vertical tortuosity of the optic nerves producing a kinked appearance with apparent entrapment of perioptic CSF within the distal optic nerve sheaths. There was no compression of the pituitary gland within the sella (i.e. no empty sella). Lumbar puncture under general anesthesia revealed a normal opening pressure of 24.2 cm H 2 O . Molecular testing revealed the same ERCC6 mutations as in her brother.
