From the Department of Ophthalmology (MJK, DWL, EYK, MA); and the Department of Obstetrics and Gynecology (JHL), Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Min Ahn, MD, PhD, Department of Ophthalmology, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjingu, Jeonju, Jeonbuk, Republic of Korea, 561–712.
Extreme high myopia with lens subluxation is rare in newborns. Congenital high myopia can be combined with systemic abnormalities. Early prenatal diagnosis of high myopia would provide the opportunity to evaluate associated or combined serious abnormalities requiring optimal postnatal management. High myopia diagnosed by prenatal ultrasound has not been previously reported with ultrasound photographs in the literature. Here, we report congenital axial high myopia detected by axial length measurement of the eyeball through prenatal ultrasound during the third trimester of pregnancy.
A 38-year-old woman, para 1-0-2-1, was referred to our obstetric clinic because her fetus was suspected to have a facial anomaly at 33 gestational weeks. Neither she nor her husband had specific individual or family histories, structural anomalies, or chromosomal abnormalities. She had delivered a healthy female infant weighing 3,200 g 1 year earlier. On fetal ultrasonography, her fetus showed exophthalmos and everted nose. At 33 weeks’ gestation, the axial length of the eyeball was 24 mm (Fig. 1). Both lenses were shown apparently. The biparietal diameter (8.31 cm) and abdominal circumference (29.07 cm) were within normal range, but the femur length (5.79 cm) was slightly shorter than that of gestational age. The amniotic fluid index was 21.51 cm. Other fetal organs were structurally normal during ultrasonography.
Figure 1. Fetal Ultrasonography Shows the Axial Length of the Eyeball Measured 24 mm at 33 Weeks’ Gestation.
Five weeks later, a male infant weighing 3,360 g was delivered by normal vaginal birth. He had Apgar scores of 8 and 10 at 1 and 5 minutes, respectively.
We performed DNA sequencing using cord blood to confirm high myopia-related syndromes, including fibroblast growth factor receptor 2 gene mutation of Crouzon syndrome, but the result was normal. External examination found gross proptosis, hypertelorism, depressed nasal bridge with everted nasal tip, and up-slanting palpebral fissures (Fig. 2A). He had complete eyelid closure. The interpupillary distance was 38 mm showing approximately 30 prism diopters of exotropia by the Krimsky method. The pupils were equally round and reactive to light without afferent pupillary defect.
Figure 2. (A) External Examination Showing Gross Proptosis, Hypertelorism, Depressed Nasal Bridge with Everted Nasal Tip, and Up-Slanting Palpebral Fissures. (B) Lens Subluxation in the Left Eye.
Slit-lamp examination found a clear cornea and slight lens subluxation in the left eye. Intraocular pressures were 19, 17, and 18 mm Hg in the right eye and 18, 19, and 18 mm Hg in the left eye, measured with a tonometer (Tono-pen; Mentor O & O, Norwell, MA) every 6 hours considering diurnal variation. Dilated fundus examination found bilateral myopic degeneration with generalized hypopigmentation, straightened retinal vessels, retinal hemorrhages, vitreous hemorrhages, and neovascularizations (Fig. 3). A-scan ultrasonography (Tomey; Tomey Corporation, Nagoya, Japan) found the axial lengths of the eyeballs to be 24.58 mm in the right eye and 26.27 mm in the left eye. The corneas were clear, with a diameter of 12 mm in each eye. Cycloplegic refraction findings of spherical equivalent were approximately 30 diopters of myopia in the right eye and 25 diopters in the left eye.
Figure 3. Fundus Shows Generalized Hypopigmentation, Straightened Retinal Vessels, Retinal Hemorrhages, Vitreous Hemorrhages, and Neovascularizations.
The infant underwent a series of tests, including measurement of height, circumference of head and chest, skull radiology, brain magnetic resonance imaging, brain ultrasonography, audiology, chromosomal analysis, and genetic evaluation. The results of all tests were normal. The parents took the infant to another hospital for further evaluation including gene study and all test results were proven to be normal again.
Four months later, the infant returned to our ophthalmology clinic because of his inability to fixate his eyes. His parents complained that he never stared at their faces. No findings showed notable differences except progressed lens subluxation in the left eye (Fig. 2B).
The mean axial length of fetal eyeballs at the age of 33 weeks’ gestation is 15.29 mm.1 The axial length of our case was 24 mm at 33 weeks of gestation, which is compatible with the size of an adult eyeball.2
We reviewed syndromes showing high myopia to make a diagnosis. From the demonstrated prenatal ultrasonographic findings, we presumed Crouzon syndrome. Prenatal ultrasound diagnosis of Crouzon syndrome by binocular diameters and exophthalmos had been introduced.3,4 Crouzon syndrome (or craniofacial dysostosis) is an autosomal dominant disorder characterized by craniosynostosis, maxillary hypoplasia, hypertelorism, strabismus, shallow orbits, and exophthalmos. It is usually caused by one of several mutations within the fibroblast growth factor receptor 2 gene.5 This may result in premature fusion of the sutures of the cranium and base of the skull, but those findings were absent in our case.
Stickler syndrome is a progressive, hereditary disorder with ocular and systemic features. Ocular findings are vitreous veil of vitreous strand due to vitreous condensation, vitreoretinal degeneration, moderate to high myopia, vitreous liquefaction, chorioretinal atrophy, retinal detachment, and cataract. Systemic findings are midfacial hypoplasia, cleft palate, hearing loss, and musculoskeletal abnormalities. Stickler syndrome is related with mutations in the COL2A1, COL9A1, COL11A1, and COL11A2 genes.6
Wagner syndrome has similar ocular manifestations as Stickler syndrome with lower risk of retinal detachment. This syndrome is related with exon 8 of the chondroitin sulphate proteoglycan 2.7
Autosomal dominant nonsyndromic high-grade myopia has been mapped to loci on 18p11.31, 12q21-q23, 17q21-q23, and 7q36.8.
Robinow syndrome is a rare congenital abnormality. It is characterized by mesomelic brachymelia, hemivertebrae, dysmorphic faces, genital hypoplasia, micropenis, clinodactyly, camptodactyly, hypoplastic nails, and moderate short stature.9,10 Craniofacial abnormalities are macrocephaly, hypertelorism, prominent eyes, down-slanting palpebral fissures, small upturned nose, long philtrum, triangular mouth with downturned angles, micrognathia, hyperplastic alveolar ridges, crowded teeth, and posteriorly rotated ears. Mutations of Retinoic acid receptor-related orphan receptor 2, a gene located on chromosome 9q22, which encodes a receptor tyrosine kinase-like orphan receptor 2, are responsible for the recessive type.11
Marfan-like connective tissue disorders are associated with mutations in the transforming growth factor-beta receptor (TGFBR) genes. Mutations in the fibrillin-1, TGFBR1, TGFBR2, COL3A1 genes cause Marfan syndrome.12
Donnai–Barrow syndrome is a rare autosomal recessive disorder first described in 1993.13 Ocular features include hypertelorism, down-slanting palpebral fissures, iris coloboma, high myopia, and retinal detachment. The extreme congenital myopia in these patients is a significant risk factor for retinal detachment.
There are more syndromes associated with myopia. The systemic features and the results of genetic study of our case did not fit any of those syndromes. We suspect it to be a variant of a well-known syndrome or unknown disease entity. Prenatal ultrasonography has greatly expanded the number of conditions capable of detection during early fetal development. The fetal eyes are identifiable by the 12th week of gestation and the fetal lenses by the 14th week. In addition to identifying prenatal abnormalities, ultrasonography can also detect normal prenatal ocular and orbital development in families in which other children were affected by congenital ophthalmic abnormalities. The information is not only crucial for parental counseling, but it is also useful to the obstetrician in assembling the appropriate members of a multidisciplinary team to manage the condition after birth. In our case, prenatal imaging detected the high myopic eye.
Management of such cases with myopia would be early diagnosis, prevention of amblyopia, and long-term follow-up for retinal detachment, which is one of the major cause of vision loss. Measuring the axial length of the eyeball by prenatal ultrasonography can be a good tool for the diagnosis of congenital high refractive error, including high ammetropias, anisometropia, and either axial myopia or axial hyperopia. Syndrome-associated anomalies should be evaluated in a fetus with high myopia.
This case illustrates that prenatal ultrasound can be useful in early detection and monitoring of a high refractive error. Postnatal ophthalmic evaluation can provide additional information regarding the etiology and severity of the refractive error and to assist the ophthalmologist in formulating a management strategy aimed at reducing the devastating effects of amblyopia.
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- Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet. 1994;8:98–103. doi:10.1038/ng0994-98 [CrossRef]
- Van Camp G, Snoeckx RL, Hilgert N, et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006;79:449–457. doi:10.1086/506478 [CrossRef]
- Meredith SP, Richards AJ, Flanagan DW, Scott JD, Poulson AV, Snead MP. Clinical characterisation and molecular analysis of Wagner syndrome. Br J Ophthalmol. 2007;91:655–659. doi:10.1136/bjo.2006.104406 [CrossRef]
- Paluru PC, Nallasamy S, Devoto M, Rappaport EF, Young TL. Identification of a novel locus on 2q for autosomal dominant high-grade myopia. Invest Ophthalmol Vis Sci. 2005;46:2300–2307. doi:10.1167/iovs.04-1423 [CrossRef]
- Robinow M, Silverman FN, Smith HD. A newly recognized dwarfing syndrome. Am J Dis Child. 1969;117:645.
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- Afzal AR, Rajab A, Fenske CD, et al. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Nat Genet. 2000;25:419–422. doi:10.1038/78107 [CrossRef]
- Faivre L, Collod-Beroud G, Loeys BL, et al. Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet. 2007;81:454–466. doi:10.1086/520125 [CrossRef]
- Patel N, Hejkal T, Katz A, Margalit E. Ocular manifestations of Donnai-Barrow syndrome. J Child Neurol. 2007;22:462–464. doi:10.1177/0883073807301933 [CrossRef]