Brief Clinical Report

Arrhythmogenic Right Ventricular Dysplasia andAnterior Polar Cataract

Raul Frances,1,2 Ana M. Rodriguez Benitez,1,2 and Daniel R. Cohen1,2*1Sanatorio Centro, Department of Ophthalmology, Facultad de Ciencias Medicas, Universidad Nacional de Rosario,Rosario, Argentina

2Instituto Argentino de Investigaciones Geneticas, Rosario, Argentina

Arrythmogenic right ventricular dysplasia(ARVD) is an autosomal dominant inheritedcardiomyopathy with incomplete pen-etrance and variable expressivity. Recently,the gene was mapped to 14q23-24. It is beingincreasingly investigated as a major causeof sudden death at a young age. Anterior po-lar cataract (APC) is a rare hereditary formof lens opacity. The locus for an APC genewas located tentatively on 14q24qter. We de-scribe a patient with a severe form of ARVDin whom asymptomatic APC was detectedby an ophthalmologic examination. His sis-ter had ARVD and similar cataracts. Par-ents were second cousins but were healthy.This is the first report of possible autosomalrecessive inheritance of ARVD. This is alsothe first time that the combination of ARVDand APC is reported. Three possibilitiesmay explain this concurrence: pleiotropy,contiguous gene syndrome, or coincidence.Our findings suggest placement of an APCgene at 14q23-24. Am. J. Med. Genet. 73:125–126, 1997. © 1997 Wiley-Liss, Inc.

KEY WORDS: arrhythmogenic right ven-tricular dysplasia; anteriorpolar cataract; cardiomyo-pathy

INTRODUCTION

Arrhythmogenic right ventricular dysplasia (ARVD)is described as an autosomal dominant cardiomyopa-thy with incomplete penetrance and variable expres-sion [Berder et al., 1995]. Recently, the abnormal genewas mapped to 14q23-24 [Rampazo et al., 1994]. The

frequency of this condition is uncertain, but some in-vestigators agree that this is an important cause ofsudden cardiac death at a young age [Thiene et al.,1988]. Anterior polar cataract (APC) is a small, usuallybilateral axial lens opacity that is more frequentlyasymptomatic and is reported in 0.4% of live-born in-fants [Chance et al., 1950]. A locus for APC is mappedto 14q24-qter, adjacent to the ARVD gene [McKusick,1994]. We describe a patient with a severe form ofARVD and asymptomatic APC. The cardiomyopathywas also present in his sister but not in his parents.Neither the parents nor the sister had APC. The par-ents were second cousins.

CLINICAL REPORT

The 27-year-old man was asymptomatic until age 10,when ventricular premature beats (VPBs) were de-tected on a routine spot examination. A 12-lead elec-trocardiogram (ECG) and 24-hour Holter monitoringshowed frequent, monomorphic VPBs. At that time, anM-mode echocardiogram showed normal cavities andmitral valve prolapse. The patient was treated withamiodarone 200 mg per day. One year ago, he came toour service for a check up. He was asymptomatic, withonly occassional pretibial edema. A blue-gray pigmen-tation of the nose attributable to amiodarone was ob-served. Jugular distension, hypophonetic heart sounds,systolic tricuspid murmur, and hepatomegaly werepresent.

The ECG demonstrated sinus rhythm, enlargementof atria and right ventricle, low-voltage QRS, frequentVPBs with left bundle branch block (LBBB) pattern,and epsilon waves in leads V2–V6. The chest radio-graph (Fig. 1) showed cardiomegaly, and a two-dimensional echocardiogram showed severe enlarge-ment of the right atrium and ventricle and moderateleft atrial enlargement. Magnetic resonance imaging(MRI) demonstrated high-density zones compatiblewith the presence of fatty tissue. A signal-averagedECG was positive. Treatment was stopped to performan exercise stress test 30 days later. The test resultswere normal, but, 3 days later, the patient showed awell-tolerated, sustained ventricular tachycardia (VT)

*Correspondence to: Daniel R. Cohen, M.D., Montevideo 1683,Rosario 2000, Argentina.

Received 21 April 1997; Accepted 21 April 1997

American Journal of Medical Genetics 73:125–126 (1997)

© 1997 Wiley-Liss, Inc.

with LBBB pattern at a cycle length of 440 msec. Aftersuccessful acute treatment with lidocaine, the patientremained on sotalol 160 mg a day and was told to avoidphysical stress. One month later, an episode of slowand sustained VT was observed on 24-hour Holtermonitoring. It was present during 6 hours while thepatient was performing his daily activities. Twomonths later, a new episode of VT with the same mor-phology and cycle length provoked hypotension anddizziness. Sotalol was discontinued, and amiodaronewas restarted. The patient is on a maintenance dose of200 mg per day. At present, the patient is in atrialfibrillation and complains only of mild edema during a2-month follow up.

After reviewing the case, we referred the patient toan ophthalmologist. The routine ocular examinationshowed a visual acuity with correction of 200/200 inboth eyes. Refraction was −0.50 × 70° in the right eyeand −0.25 × 70° in the left eye. A bilateral, reddish,star-shaped opacification of the crystalline lens with adiameter of approximately 2.5 mm compatible withAPC was observed (Fig. 2). No chromosome abnormali-ties were detected by high-resolution banding proce-dure in this family.

The patient’s parents and sister also underwent car-diac and ocular examination. ARVD and APC were notdetected in the parents after performing physical ex-amination, ECG, chest film, two-dimensional echocar-diogram, cardiac MRI, and ophthalmologic examina-tion.

ARVD was diagnosed in the sister. She had two epi-sodes of symptomatic, monomorphic, sustained VTwith LBBB pattern. The ECG showed low-voltage QRSin limb leads and inverted T waves in V1–V3. The chestradiograph demonstrated mild-to-moderate RV en-largement. Both echocardiogram and MRI demon-strated moderately dilated RV, mildly dilated rightatrium, and mild tricuspid regurgitation. Left cavitieswere normal. On the anterior and inferior wall near theapex, a high-density protonic zone compatible withfatty tissue was observed. The ocular examinationdemonstrated an asymptomatic, unusual, linear-shaped opacification of the crystalline lens in the an-terior and posterior subcapsular zones.

DISCUSSION

To the best of our knowledge, this is the first reportof possible autosomal recessive inheritance of ARVDand APC. Our observations are supported by the factthat both affected siblings were born to healthy, con-sanguineous parents without other affected relatives.Parents are second cousins with a coefficient of rela-tionship of 1/32 and an inbreeding coefficient of 1/64.

The very uncommon occurence of both disorders inthe general population suggests that this is not concur-rence but is due either to pleiotropy or to a contiguousgene syndrome. This is supported by recent humangene mapping [McKusick, 1994], in which the locus ofthe APC gene is assigned close to the locus of ARVD onchromosome 14.

The APC gene is classified as L (limbo) according tohuman gene mapping [McKusick, 1994] on the basis ofits supposed, but not proved, placement on the chromo-some 14. The clinical association with ARVD shown inour patient strongly supports its location adjacent tothe ARVD gene on chromosome 14q24-qter.

ACKNOWLEDGMENTS

We thank Victor Penchaszadeh, M.D., for the out-standing review of this paper. We also thank OscarBottasso, M.D., Ph.D., for his friendly suggestions.

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McKusick VA (1994): ‘‘Mendelian Inheritance in Man. A Catalog of HumanGenes and Genetic Disorders.’’ Baltimore: The Johns Hopkins Univer-sity Press, 261.

Rampazzo A, Nava A, Danieli GA, Gianfranco B, Daliento L, Fasoli G,Scognamiglio R, Corrado D, Thiene G (1994): The gene for arrhythmo-genic rith ventricular cardiomyopathy maps to chromosome 14 q23-24.Hum Mol Genet 3:959–962.

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Fig. 1. Chest radiograph showing severe cardiomegaly in a patient witharrhythmogenic right ventricular dysplasia.

Fig. 2. Asymptomatic, star-shaped, anterior polar cataract observedduring an ophthalmologic examination in a patient with arrhythmogenicright ventricular dysplasia.

126 Frances et al.