Trisomy 18, also known as Edwards syndrome, is a severe disorder that has been associated with anomalies in all organ systems. The ophthalmic literature regarding Edwards syndrome remains scarce, largely because of the significantly decreased life span associated with the disorder. For that reason, most of the ophthalmic literature has focused on postmortem histopathologic findings. We now report the first case of trisomy 18 associated with a clinically detectable optic nerve pit.
A female neonate with a birth weight of 2,150 g was born by cesarean section to a healthy 40-year-old woman, gravida 3, para 3, at 38 weeks of gestation. Trisomy 18 had been diagnosed by prenatal genetic testing. The delivery was complicated due to a nuchal cord. There was no family history of abortions or congenital anomalies.
The neonate had Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Multiple congenital anomalies were noted on physical examination, including short sternum, low-set ears, micrognathia, hypotonia, clinidactily in both hands, and hypoplastic nails.
Two-dimensional echocardiogram performed demonstrated a patent foramen ovale, ventricular septal defect, patent ductus arteriosus, and dysplatic aortic valve. Abdominal sonogram revealed a horseshoe kidney.
Magnetic resonance imaging of the brain showed multiple cystic spaces in the left cerebral hemisphere. No evidence of intracranial hemorrhage or mass effect was observed. The orbital portion of the study did not show any abnormalities.
Ophthalmology evaluation was requested due to the patient’s diagnosis of trisomy 18. External ophthalmologic examination was remarkable for bilateral narrowed palpebral fissures. The lower eyelids were notable for punctal agenesis bilaterally. The pupils were corectopic without reaction to light. The cornea was clear, the anterior chamber was deep, and the lens was clear bilaterally. Indirect ophthalmoscopy was remarkable for bilateral inferior peripapillary retinochoroidal hypopigmentation that was more pronounced in the left eye as depicted in Figures 1 and 2 . The optic nerve head had a cup-to-disc ratio of 0.7 in the left eye with an associated temporal optic nerve pit. No subretinal or intraretinal fluid was clinically detectable. Ocular echography showed optic nerve cupping in the left eye (Figure 3 ). No subretinal or intraretinal fluid was detected by echography.
Figure 1. Inferior peripapillary retinochoroidal hypopigmentation in the right eye.
Figure 2. Inferior peripapillary retinochoroidal hypopigmentation with temporal optic nerve pit (arrow) in the left eye.
Figure 3. Posterior segment ultrasound image showing optic nerve cupping (arrow) in the left eye.
Edwards et al. described the first case of cytogenetically documented trisomy 18 in 1960.1 Edwards syndrome is a severe disorder that is characterized by congenital anomalies in all of the organ systems. It is the second most common trisomy after trisomy 21. Classic physical characteristics include prominent occiput, short eye fissures with ptosis, micrognathia, auricular malformations, clenched fist with overlapping fingers, undeveloped thumbs, and rocker-bottom feet.
A comprehensive and systematic review of the literature was performed. The Pubmed.org search engine was used and the terms “trisomy 18, Edwards syndrome, ocular, ophthalmology, ophthalmologic, ophthalmic, optic nerve pit, optic nerve pit, pediatric, children, and eye” were used in all possible combination orders. Once an article was found in PubMed, the related citations tab was used to search for related articles. All related citations that were relevant to our article were again researched using the related citation tabs. The same algorithm was applied until no more related articles were found. The articles and the references of each article were reviewed. Multiple articles that were not originally in PubMed were found via article references. All related references that were relevant to our article were again searched. The same algorithm was applied until no more related articles were found. International journals were searched via Ophthalmic Literature JournalSeek and Zentralblatt für die gesamte Ophthalmologie und ihre Grenzgebiete in the same fashion.
Extensive scientific contributions regarding trisomy 18 have been reported in literature since the original description of the syndrome by Edwards et al.1 Previously described ophthalmic manifestations include corneal opacities, retinal folds, microphthalmos, cataracts, colobomas, persistent hyaloid vasculature, glaucoma, strabismus, nystagmus, and ptosis.2,3 Most of the ophthalmic literature has focused on the postmortem histopathologic findings.2–7 Due to the significantly decreased survival of patients with trisomy 18, the clinical ophthalmologic reports remain scarce.
Velzeboer et al. suggested the possibility of an optic nerve pit in a histopathologic report of trisomy 18.7 However, to our knowledge, ours is the first clinical and photographic documentation of an optic nerve pit in a neonate and in Edwards syndrome. It has generally been accepted that optic nerve pits are a congenital anomaly. However, the pathophysiological background of optic nerve pits remains unclear and controversial. Previous reports have suggested that optic nerve pits represent a more benign variant of optic disc coloboma, a result of incomplete closure of the optic fissure during development.8 Conversely, in a review of 75 cases, Brown et al. concluded that the lack inferonasal pits cast doubts as to whether the pits are truly colobomas.9 Furthermore, Brodsky suggested that it is unlikely that optic nerve pits represent a variant of colobomatous changes because they usually lack systemic associations and are rarely found with iris or retinochoroidal colobomas.10 Vision loss from optic nerve pits is due to subretinal fluid, which is thought to originate from either the vitreous cavity10 or the subarachnoid space.11
We report an association between optic nerve pits and trisomy 18. The bilateral inferior peripapillary retinochoroidal hypopigmentation suggests the possibility of incomplete bilateral optic nerve colobomas. Studies investigating the embryological abnormalities in Edwards syndrome and further documentation of optic nerve pits during childhood could lead to better understanding of the patho-physiology of optic nerve pits.
- Edwards JH, Harden DG, Cameron AH, Crosse VM, Wolff OH. A new trisomic syndrome. Lancet. 1960;1:787–789 doi:10.1016/S0140-6736(60)90675-9 [CrossRef] .
- Calderon JP, Chess J, Borodic G, Albert DM. Intraocular pathology of trisomy 18 (Edwards syndrome): report of a case and review of literature. Br J Ophthalmol. 1983;67:162–169 doi:10.1136/bjo.67.3.162 [CrossRef] .
- Ginsberg J, Bove K, Nelson R, Englender GS. Ocular pathology of trisomy 18. Ann Ophthalmol. 1971;3:273–279.
- Mullaney J. Ocular pathology in trisomy 18 (Edwards’ syndrome). Am J Ophthalmol. 1973;76:246–254.
- Ginsberg J, Bofinger MK, Roush JR. Pathologic features of the eye in Down’s syndrome with relationship to other chromosomal anomalies. Am J Ophthalmol. 1977;83:874–880.
- Pe’er J, Braun JT. Ocular pathology in trisomy 18 (Edwards’ syndrome). Ophthalmologica. 1986;192:176–178 doi:10.1159/000309637 [CrossRef] .
- Velzeboer CM, van der Harten JJ, Koole FD. Ocular pathology in trisomy 18: a histopathological report of three cases. Ophthalmic Paediatr Genet. 1989;10:263–269 doi:10.3109/13816818909009881 [CrossRef] .
- Lin CC, Tso MO, Vygantas CM. Coloboma of optic nerve associated with serous maculopathy: a clinicopathologic correlative study. Arch Ophthalmol. 1984;102:1651–1654 doi:10.1001/archopht.1984.01040031341023 [CrossRef] .
- Brown GS, Shields JA, Goldberg RE. Congenital pits of the optic nerve head: II. Clinical studies in humans. Ophthalmology. 1980;87:51–65.
- Brodsky MC. Congenital optic disc anomalies. Surv Ophthalmol. 1994;39:89–112 doi:10.1016/0039-6257(94)90155-4 [CrossRef] .
- Gass JDM. Serous detachment of the macula secondary to congenital pit of the optic nerve head. Am J Ophthalmol. 1969;67:821–841.