Familial unilateral ectopia lentis

John W. Simon, MD,a Jeremy M. Cotliar,a and Leah W. Burke, MDb

Ectopia lentis is almost always a bilateral condition, although it may be asymmetric in some cases of Marfan syndrome.1,2 Unilateral ectopia lentis has been associated with trauma and with intraocular tumors.3 We report two siblings with isolated unilateral ectopia lentis who had no evidence of underlying abnormality or of trauma.

Patient 2
A 4-month-old boy, the brother of Patient 1, presented to the same ophthalmology service because of iridodonesis in the right eye. Examination showed a temporal dislocation of the right lens with one-quarter of the pupil aphakic. The left lens was normally positioned on slit-lamp examination, ophthalmoscopy, and retinoscopy after dilation of the pupils. The child preferred xation with the left eye. Cycloplegic refraction yielded 13.00 OD and 1.50 OS. Glasses and patching of the left eye were prescribed, but the child would not tolerate either. At age 1 year, the child underwent limbal lensectomy on the right eye. He continued to resist all attempts at patching but did tolerate his aphakic contact lens. His corrected visual acuity, 7 years postoperatively at age 9, was counting ngers in the right eye and 20/30 in the left eye.

ctopia lentis is frequently encountered in association with systemic, heritable conditions, including Marfan syndrome, homocystinuria, Weill-Marchesani syndrome, and hyperlysinemia. Simple ectopia lentis and ectopia lentis et pupillae are both autosomal-dominant conditions with abnormalities limited to the eye. The assessment of children with ectopia lentis should include evaluations for these conditions and examinations of close family members.

Patient 1
A 3-year-old girl who presented to the pediatric ophthalmology service of the Albany Medical College with a 6-week history of intermittent right esotropia was found to have a temporal dislocation of the right lens. Approximately one-quarter of the pupil was aphakic. The left lens was normally positioned on slit-lamp examination, ophthalmoscopy, and retinoscopy after dilation of the pupils. Her uncorrected visual acuity measured 4/700 in the right eye and 20/30 in the left eye. The cycloplegic refraction, 8.00 in the right eye and plano in the left eye, was prescribed as spectacles, and the left eye was patched. After 11 months, the amblyopia had not improved, and a limbal lensectomy was performed on the right eye. The child wore an aphakic contact lens, which corrected the visual acuity to 20/100 at age 5. When she was last seen, 9 years postoperatively at age 12, her visual acuity measured 20/400 in the right eye and 20/20 in the left eye.

Special Testing
The parents and pediatrician were initially questioned regarding the possibility of trauma, including child abuse, but there was no reason for suspicion by history or by physical examination. Both children were referred for genetic evaluation. Physical assessment showed no systemic illness and there was no morphologic evidence of Marfan syndrome or homocystinuria. There was no cardiac abnormality. Plasma amino acids, including homocystine, were normal. Linkage analysis was performed using several anking and intragenic markers that indicated that both children received the same alleles from their parents. A sample was then sent from Patient 1 for DNA analysis and all 65 exons of the FBN1 gene were evaluated using a heteroduplex analysis of the polymerase chain reaction products. No mutation was detected. The parents had normal eye examinations.

Discussion
The two patients reported here, who have no other siblings, appear to have isolated, unilateral ectopia lentis. The most common syndromes involving ectopia lentis are Marfan syndrome and homocystinuria. Mutations in the FBN1 gene are found in typical Marfan syndrome as well as in rare familial cases of isolated autosomal-dominant ectopia lentis. These two siblings do not t the clinical criteria for Marfan syndrome or homocystinuria nor do they have a detectable mutation in the FBN1 gene.4 The possibility of trauma, especially nonaccidental trauma, is difcult to exclude with certainty but is especially unlikely given the exactly duplicated unilateral lens dislocations in these two siblings. Additionally, there

Author afliations: aAlbany Medical College, Department of Ophthalmology, Lions Eye Institute, Slingerlands, New York; and bDepartment of Genetics, University of Vermont College of Medicine, Albany, New York Submitted February 9, 2007. Revision accepted May 8, 2007. Published online August 28, 2007. Reprint requests: John W. Simon, MD, Lions Eye Institute, 1220 New Scotland Road, Suite 202, Slingerlands, NY 12159 (email: SimonJ@mail.amc.edu). J AAPOS 2007;11:620-621. Copyright 2007 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2007/$35.00 0 doi:10.1016/j.jaapos.2007.05.008

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has never been any other suggestion of physical trauma in either child through a 10-year follow-up period. We believe that these children have unilateral simple ectopia lentis that appears to follow an autosomal-recessive inheritance pattern not involving the FBN1 gene. Perhaps because of the unilateral involvement in both children, the advanced age of Patient 1, and the noncompliance of Patient 2, the associated amblyopia has proved difcult to manage, even with aggressive occlusion, optical correction, and early lensectomy. Ophthalmologists should be aware that isolated unilateral ectopia lentis can be familial. Family members should be evaluated accordingly.

References
1. Burgio RG, Martini A, Cetta G, Zanaboni G, Vitellaro L, Danesino C. Asymmetric Marfan syndrome. Am J Med Genet 1988;30:905-9. 2. Tsipouras P, Del Mastro R, Sarfarazi M, Lee B, Vitale E, Child AH, et al. Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the brillin genes on chromosomes 15 and 5: The International Marfan Syndrome Collaborative Study. N Engl J Med 1992;326:905-9. 3. Gupta NK, Simon JW, Walton DS, Augsburger JJ. Bilateral ectopia lentis as a presenting feature of medulloepithelioma. J AAPOS 2001; 5:255-7. 4. Ades LC, Holman KJ, Brett MS, Edwards MJ, Bennetts B. Ectopia lentis phenotypes and the FBN1 gene. Am J Med Genet 2004;126A: 284-9.

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