ABC | Volume 110, Nº1, January 2018

Review Article Oliveira et al Association of congenital heart diseases with ophthalmologic changes Arq Bras Cardiol. 2018; 110(1):84-90 Phace syndromes, whereas the posterior segment was more frequently affected in the Turner, Alagille, Marfan, Bloch and Peters syndromes.Ocular findings associatedwith these syndromes were: strabismus (43.4%), cataract (28.0%), abnormalities of eyelid position and shape (28%), nystagmus (21.7%), refractive errors (19.5%), glaucoma (19.5%), and hypertelorism (19.5%). Discussion Due to their clinical variability, congenital cardiac malformations may progress asymptomatically to severe heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance. However, so far, few studies have investigated more specific extracardiac factors, such as ophthalmologic ones. In light of the potential associations between cardiologic and ophthalmologic changes, both cardiologist and ophthalmologist should be aware of concomitant signs that may indicate certain syndromes or their severity. Among these genetic syndromes, the most frequently described cardiac manifestations were interatrial and interventricular communications, patent ductus arteriosus, pulmonary artery stenosis, and tetralogy of Fallot, whereas the most common ocular diseases were strabismus, cataract, eyelid disturbances, nystagmus, glaucoma, refractive errors and hypertelorism. Mean number of ocular findings per genetic syndrome associated with heart disease was 3.5 among uncommon syndromes, and 4.6 among the most common syndromes. A recent systematic review 39 showed that few studies have assessed the prevalence of ocular findings in CHD that are not associatedwith genetic syndrome. The prevalencewas estimated at 32.5%, with cataract, strabismus, and retinopathy as the main consequences described. 39 In case of genetic syndromes, such estimation is limited due to the scarcity of series and reports. Down syndrome had the highest number of patients described – more than 6,000 patients in the 6 articles analyzed. This is the most common syndrome in newborns with an incidence of 1/660 live births. In 95% of cases, Down syndrome is caused by nondisjunction during maternal meiosis I, resulting three copies of chromosome 21 in each cell; 4% of these cases are related to gene translocations and 1% to mosaicism. The frequency of CHDs in children with trisomy 21 is variable in the literature, varying from 20% to over 60%. 40 These children are known to be prone to strabismus, hypertelorism, upslanted palpebral fissures, epicanthic fold, supernumerary retinal vessels, Brushfield spots, refractive errors, cataract, nystagmus, amblyopia. In general, the approach of children with genetic syndrome is more complex, requiring the simultaneous involvement of many medical specialties. These children should be followed-up by a multidisciplinary staff, which would be responsible for the diagnosis, the therapeutic project and patients’ follow-up. Among these study’s limitations, the most important is the publication bias of the reviewed articles. Although available published data do not enable a meta-analysis, the summary of these findings enables the compilation of data published in sporadic reports into a unique text, resizing the problem dimension and demanding more comprehensive studies. We performed an extensive article search, without language restrictions, and this sensitivity was a strength of this study. However, an intrinsic limitation of a systematic review is the quality of the studies included. Conclusion This study demonstrated the variety of cardiologic and ophthalmologic findings associated with these genetic syndromes, emphasizing the importance of this simultaneity, and that signs in the eye and appendages and cardiac signs require an integrated approach. Since these cases can cause severe functional disturbances and high morbidity, their routine assessment should include an ophthalmologic examination. Primary detection of any of these ocular signs can determine the investigation of a so far unrecognized cardiac change. Author contributions Conception and design of the research: Oliveira PHA, Souza BS, Pacheco EN, Menegazzo MS, Corrêa IS, Zen PRG, Rosa RFM, Cesa CC, Pellanda LC, Vilela MAP; Acquisition of data, Analysis and interpretation of the data, Statistical analysis, Obtaining financing, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Souza BS, Pacheco EN, Menegazzo MS, Corrêa IS, Zen PRG, Rosa RFM, Cesa CC, Pellanda LC. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This study is not associatedwith any thesis or dissertationwork. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Fundação Universitária de Cardiologia do Rio Grande do Sul under the protocol number 101593/2013-9. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 88