Aims: To investigate whether ocular anomalies are associated with congenital heart defects in children with Downâ€™s syndrome. 



Methods: 58 children with Downâ€™s syndrome were entered into a retrospective observational study. Children were assigned to heart defect groups based on medical records. Optometric tests had previously been carried out at the homes of the children. 



Results: A relation between congenital cardiac defects, myopia, and nystagmus was observed. Heart problems were not related to accommodative insufficiency, hyperopia, or strabismus. 



Conclusion: In children with Downâ€™s syndrome heart defects were associated with both myopia and nystagmus

Bromham, Nathan R

Cregg, M.

Fraser, William

Webb, Elspeth Valma Jocelyn

Woodhouse, J. M.

Online Research @ Cardiff

doi:10.1136/bjo.86.12.1367  2002;86;1367-1368 Br. J. Ophthalmol.  N R Bromham, J M Woodhouse, M Cregg, E Webb and W I Fraser    Down’s syndromeHeart defects and ocular anomalies in children with http://bjo.bmjjournals.com/cgi/content/full/86/12/1367Updated information and services can be found at:  These include: References   http://bjo.bmjjournals.com/cgi/content/full/86/12/1367#BIBLThis article cites 17 articles, 1 of which can be accessed free at: Rapid responses http://bjo.bmjjournals.com/cgi/eletter-submit/86/12/1367You can respond to this article at:  serviceEmail alertingtop right corner of the article Receive free email alerts when new articles cite this article - sign up in the box at theTopic collections (1955 articles) Other ophthalmology  (1477 articles) Children   Articles on similar topics can be found in the following collections  Notes    http://www.bmjjournals.com/cgi/reprintformTo order reprints of this article go to:  http://www.bmjjournals.com/subscriptions/ go to: British Journal of OphthalmologyTo subscribe to  on 15 November 2005 bjo.bmjjournals.comDownloaded from SCIENTIFIC CORRESPONDENCEHeart defects and ocular anomalies in children withDown’s syndromeN R Bromham, J M Woodhouse, M Cregg, E Webb, W I Fraser. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Br J Ophthalmol 2002;86:1367–1368Aims: To investigate whether ocular anomalies are associ-ated with congenital heart defects in children with Down’ssyndrome.Methods: 58 children with Down’s syndrome wereentered into a retrospective observational study. Childrenwere assigned to heart defect groups based on medicalrecords. Optometric tests had previously been carried outat the homes of the children.Results: A relation between congenital cardiac defects,myopia, and nystagmus was observed. Heart problemswere not related to accommodative insufficiency, hyper-opia, or strabismus.Conclusion: In children with Down’s syndrome heartdefects were associated with both myopia and nystagmus.Ophthalmological anomalies are common in individualswith Down’s syndrome including refractive error, 1nystagmus,2 strabismus,3 and cataract.4 The incidenceand severity of these defects is variable and it is not knownwhy some individuals develop ocular problems and others donot, given that the underlying chromosomal abnormality isalmost always identical.Some authors argue that the characteristic traits of Down’ssyndrome result from a combination of gene dosage effects asa result of extra copies of genes on chromosome 21.5 Variabil-ity in the ocular features of Down’s syndrome could relate topolymorphism in these genes. Others believe the extrachromosomal material causes a generalised disruption in thegenetic balance of cells.6 From this viewpoint non-specificdevelopmental instability following aneuploidy accounts forocular anomalies in Down’s syndrome.Refractive error is common in Down’s syndrome, showinggreat variability between individuals. Gardiner7 suggested thatthe myopia seen in some children with Down’s syndrome wasrelated to the characteristic congenital heart defects of thesyndrome. Pires da Cunha and Belmiro de Castro Moriera8found that children and teenagers with Down’s syndrome andcardiac malformations had more myopia than those withoutsuch malformations. These studies suggest that heart defectsare related in some way to the ocular manifestation of Down’ssyndrome. This study aimed to investigate the potentialassociation between congenital heart defects and optometricanomalies in a group of children with Down’s syndrome.PATIENTS AND METHODSA retrospective observational study was conducted at theDepartment of Optometry and Vision Sciences of Cardiff Uni-versity. The recruitment and experimental protocols for thestudy were conducted in compliance with the Declaration ofHelsinki and approved by local ethics research committees.Since 1991 the visual development of a cohort of childrenwith Down’s syndrome has been studied at the Department ofOptometry and Vision Sciences of Cardiff University. The par-ents of the children from this cohort were contacted by postand asked about any history of heart problems in their child.Medical records were checked for those children who werereported as having a heart defect. A total of 58 children, agedbetween 1 and 9 years, were classified into groups according tothe heart defects recorded in the medical records. All childrenhad full trisomy 21.Optometric tests were carried out at the homes of the chil-dren. Refractive error was measured using Mohindraretinoscopy.9 The equivalent sphere of the right eye was usedto for statistical analysis. Myopia was defined as a refraction of−0.50D or greater, and hyperopia as a refraction of +2.00D orgreater.Accommodation was measured using modified Nott dy-namic retinoscopy.10 The accommodative error index (AEI)11was used to describe accommodative inaccuracy. AEI greaterthan 0.75 dioptres was considered as accommodative insuffi-ciency.Eye motility was examined by observing the child’s eyemovements when fixating a moving target. The presence ofnystagmus was noted. Eye alignment was assessed usingHirchberg’s corneal reflex and the cover test at near.Statistical analysis was conducted using the χ2 test. Fisher’sexact test was used where low subject numbers precluded theuse of the χ2 test.Table 1 Frequency of ocular anomalies both in the group as a whole and in thechildren with heart defectsOcular abnormality Total casesCases with heartdefectsAccommodative insufficiency: AEI >0.75 dioptres 46 26Hyperopia >2 dioptres 27 13Myopia >0.5 dioptres 6 6Anisometropia >2 dioptres 1 1Esotropia 13 7Intermittent esotropia 12 7Intermittent exotropia 2 2Nystagmus 11 91367www.bjophthalmol.com on 15 November 2005 bjo.bmjjournals.comDownloaded from RESULTSThe frequency of ocular anomalies and heart defects is shownin Table 1. A total of 31 children had congenital heart defects;27 children had no such defects. The most common ocularfinding was accommodative insufficiency followed by refrac-tive error, strabismus, and nystagmus.Myopia and nystagmus were significantly associated withheart defects. There was no significant association betweenheart defects and accommodative insufficiency, hyperopia, orstrabismus.All six observed cases of myopia were seen in children withheart defects. The frequency of myopia among the childrenwith cardiac defects was significantly greater than among thechildren with no heart problems (p=0.018, Fisher’s exacttest).The children with cardiac defects were more likely to havenystagmus than those without cardiac problems. Of the 11children with nystagmus, nine had a heart defect (p=0.026, χ2test). The myopic children were also more likely to havenystagmus than the non-myopes; five of the six myopes in thecohort had nystagmus (p=0.001, Fisher’s exact test).DISCUSSIONThis study found both myopia and nystagmus to be associatedwith heart defects in children with Down’s syndrome. Heartdefects were not related to accommodative insufficiency,hyperopia, or strabismus in our cohort.The clinical association between endocardial cushiondefects and trisomy 21 suggests that genes located onchromosome 21 contribute to the development of the heart.12Several genes have been proposed as candidates for congenitalheart disease in Down’s syndrome, consistent with the “gene-dosage” effects hypothesis of Down’s syndrome traits.5 Geneticpolymorphisms related to heart defects could confer anincreased risk of myopia. Davies et al13 reported an associationbetween variation in the COL6A1 gene region and congenitalheart defects in Down’s syndrome. COL6A1 codes for part ofcollagen VI, a component of many ocular tissues.14 Down’ssyndrome cell adhesion molecule (DSCAM) has also beenconsidered as a candidate gene for heart defects in Down’ssyndrome.15 DSCAM is widely expressed in the developingnervous system, including the visual pathways, and may beinvolved in the regulation of myelination.16The co-occurrence of particular traits in Down’s syndromemay reflect increased developmental instability rather thanspecific gene-dosage effects. Amplified sensitivity to geneticand environmental forces during early development couldresult in both heart and ocular abnormalities. Studies of riskfactors in early pregnancy and cardiac malformations ininfants with Down’s syndrome have proposed maternal ciga-rette smoking17 and maternal age18 as risk factors. No studieshave examined risk factors for ocular anomalies in Down’ssyndrome.Myopia and nystagmus can occur following damage to thevisual pathways. Their association with heart defects in thepresent study raises the possibility of such damage secondaryto the cardiac problem. Using ophthalmoscopy the presentstudy did not observe fundus abnormalities beyond thespoke-like blood vessel arrangement around the optic discoften seen in Down’s syndrome.4 The pupils were not dilatedin the present study and it is conceivable that some anomalieswere not detected.Children with Down’s syndrome and heart defects weremore likely than those without defects to develop myopia andnystagmus in the first 9 years of life. This is of significance tothe clinician given the degree to which myopia can progress inDown’s syndrome, especially since advances in the manage-ment of cardiac defects mean that most of these children aresurviving early childhood. The Down Syndrome MedicalInterest Group publishes ophthalmic surveillance guidelinesfor people with Down’s syndrome.19 These recommend thatvisual behaviour is monitored by a paediatrician during thefirst year of life, with a formal ophthalmological review duringthe second year. Those with no abnormalities at the firstreview should have a further full ophthalmological reviewaround the age of 4 years. We believe that adherence to theserecommendations is important, especially for children withheart defects.ACKNOWLEDGEMENTSThis work was supported in part by grants from the Community Fundin collaboration with Mencap, and by the Medical Research Council,UK. The authors thank Professor Mike Creasey of the CytogeneticsDepartment, University Hospital of Wales for his help in recruitmentfor the study. We also thank the children and their families for theirparticipation.. . . . . . . . . . . . . . . . . . . . .Authors’ affiliationsN R Bromham, J M Woodhouse, M Cregg, Department of Optometryand Vision Sciences, Cardiff University, Cardiff, UKE Webb, Department of Child Health, University of Wales College ofMedicine, Cardiff, UKW I Fraser, Welsh Centre for Learning Disabilities, University of WalesCollege of Medicine, Cardiff, UKCorrespondence to: Nathan R Bromham, Department of Optometry andVision Sciences, Cardiff University, Cardiff CF10 3NB, UK;bromham@cf.ac.ukAccepted for publication 19 July 2002REFERENCES1 Woodhouse JM, Pakeman VH, Cregg M, et al. Refractive errors inyoung children with Down syndrome. Optom Vis Sci 1997;74:844–51.2 Wagner RS, Caputo AR, Reynolds RD. Nystagmus in Down’s syndrome.Ophthalmology 1990;97:1439–43.3 Haugen OH, Hodvig G. Strabismus and binocular function in childrenwith Down syndrome. A population-based, longitudinal study. ActaOphthalmol Scand 2001;79:133–9.4 Fierson WM. Ophthalmological aspects. In: Van Dynke DC, Lang DJ,Heide F, et al, eds. Clinical perspectives in the management of downsyndrome. 1st ed. New York: Springer-Verlag; 1990:26–54.5 Reeves R, Baxter L, Richtsmeier J. Too much of a good thing:mechanisms of gene action in Down syndrome. Trends Genet2001;17:83–8.6 Shapiro BL. Down syndrome—a disruption of homeostasis. Am J MedGenet 1983;14:241–69.7 Gardiner PA. Visual defects in cases of Down’s syndrome and in othermentally handicapped children. Br J Ophthalmol 1967;51:469–74.8 Pires da Cunha R, Belmiro de Castro Moriera J. Ocular findings inDown’s syndrome. Am J Ophthalmol 1996;122:236–44.9 Mohindra I. A technique for infant examination. Am J Optom PhysiolOptics 1975;54:319–22.10 Cregg M, Woodhouse JM, Pakeman VH, et al. Accommodation andrefractive error in children with Down syndrome: cross-sectional andlongitudinal studies. Invest Ophthalmol Vis Sci 2001;42:55–63.11 Chauhan K, Charman WN. Single figure indexes for the steady-stateaccommodative response. Ophthalmic Physiol Opt 1995;15:217–21.12 Klewer SE, Krob SL, Kolker SJ, et al. Expression of type VI collagen inthe developing mouse heart. Dev Dyn 1998;211:248–55.13 Davies GE, Howard CM, Farrer MJ, et al. Genetic variation in theCOL6A1 region is associated with congenital heart defects in trisomy 21(Down’s syndrome). Ann Hum Genet 1995;59:253–69.14 Marshall G, Konstas A, Lee W. Collagens in ocular tissues. Br JOphthalmol 1993;77:515–24.15 Barlow GM, Chen XN, Shi ZY, et al. Down syndrome congenital heartdisease: a narrowed region and a candidate gene. Genet Med2001;3:91–101.16 Saito Y, Akira O, Masashi M, et al. The developmental and agingchanges of Down’s syndrome cell adhesion molecule expression innormal and Down’s syndrome brains. Acta Neuropathol2000;100:654–64.17 Torfs CP, Christianson RE. Maternal risk factors and major associateddefects in infants with Down syndrome. Epidemiology 1999;10:264–70.18 Kallen B, Mastroiacovo P, Robert E. Major congenital malformations inDown syndrome. Am J Med Genet 1996;65:160–6.19 Dennis J, ed. DSMIG guidelines for essential medical surveillance.2002. www.dsmig.org.uk/publications/guidelines.html (accessed 31May 2002).1368 Bromham, Woodhouse, Cregg, et alwww.bjophthalmol.com on 15 November 2005 bjo.bmjjournals.comDownloaded from 

Heart defects and ocular anomalies in children with Down's syndrome

https://orca.cardiff.ac.uk/id/eprint/5087/1/Bromham.pdf

Heart defects and ocular anomalies in children with Down's syndrome

Abstract

Similar works

Full text

Available Versions

Online Research @ Cardiff