Persistent Truncus Arteriosus in MonozygoticTwins: Case Report and Literature Review

C. Mas,1 M.B. Delatycki,2 and R.G. Weintraub1*1Department of Cardiology, Royal Children’s Hospital, Melbourne, Australia2Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Australia

We report on a pair of monozygotic twinswith persistent truncus arteriosus. Theyhad no evident clinical signs of DiGeorgesyndrome. Pathologic examination of theplacenta and DNA analysis in chromosomes7, 8, and 15 was consistent with monozygos-ity. Fluorescence in situ hybridization testwas negative for chromosome 22q11 micro-deletion. Family history revealed a femalecousin with tetralogy of Fallot. The isolatedpresence of this conotruncal abnormality inmonozygotic twins is extremely rare. Thegenetic considerations are discussed. Am. J.Med. Genet. 82:146–148, 1999.© 1999 Wiley-Liss, Inc.

KEY WORDS: persistent truncus arterio-sus; deletion 22q11; DiGeorgesyndrome; twins

INTRODUCTION

Persistent truncus arteriosus (PTA) is a rare cardiacmalformation accounting for 0.4–1% of all congenitalheart defects [Mair et al., 1995]. Conotruncal cardiacmalformations (CTHM) can appear repeatedly in thesame family with a recurrence rate among siblings ofindex cases between 6–13% [Brunson et al., 1978;Ferry et al., 1994; Goodyear, 1961; Pierpont et al.,1988; Shapiro et al., 1981]. The possibility of autosomalrecessive inheritance to explain this observed recur-rence rate has been suggested previously [le Marec etal., 1989; Rein and Sheffer, 1994].

The association of PTA with DiGeorge syndrome infamilies also has been described [Rohn et al., 1984].Two descriptions of monochorionic twins with PTA andmajor associated anomalies were found. Of these, onepair of twins, arising from a consanguineous marriage,

had PTA in association with major skeletal anomalies(sirenomelia in one, phocomelia and other limb anoma-lies in the other) [Raghavan et al., 1983]. Other authorshave reported monozygotic twins with PTA and majorcardiovascular anomalies (single ventricle, single atrio-ventricular valve, single atrium) [Giustra and Tosti,1939]. We found a single report in which the twins weremonozygotic and had isolated PTA [Benesova and Sikl,1954]. A recent report described dizygotic twins withisolated PTA [Lang et al., 1991]. This report describesa case of monozygotic (monochorionic/diamniotic) twinswith isolated PTA.

CASE REPORT

Female twins (III-8 and III-9, Fig. 1) were born tononconsanguineous Caucasian parents following anuneventful pregnancy. The 27-year-old primigravidmother did not receive any medication, suffered no ill-ness during the pregnancy, and was not exposed to anyidentifiable teratogen. A female first degree cousin wasrecently born with tetralogy of Fallot (III-7, Fig. 1). Thebabies were born at 38 weeks gestation by normal vagi-nal delivery and were in good condition at birth. Pla-cental and membrane analysis demonstrated a singlechorion and double amnion.

Twin 1 was noted to have a cardiac murmur on day1 of life and echocardiography demonstrated type IPTA with a right aortic arch. The truncal valve wasmarkedly thickened and dysplastic, with significantaortic regurgitation present. Urgent surgical repair ofthe PTA was required at 3 weeks of age because ofsevere congestive heart failure. At operation a normalthymus was noted to be present. Preoperative serumcalcium levels and total lymphocyte count, including Tcell markers, were normal. Her karyotype was 46,XXwith no evidence of a chromosome 22 microdeletion(D22S75 Oncor, Gaithersburg, MD) using fluorescencein situ hybridization (FISH). At 10 months of age she isclinically well, but is being treated with Enalapril be-cause of significant aortic regurgitation.

Twin 2 developed a murmur and congestive heartfailure at 6 weeks of age. Echocardiography revealed atype I PTA with right aortic arch and a well-formedtruncal valve. Elective surgical repair was undertakenshortly afterwards. Serum calcium levels and lympho-

Contract grant sponsor: Caja Costarricense de Seguro Social,San José, Costa Rica.

*Correspondence to: Robert Weintraub, M.D., Department ofCardiology, Royal Children’s Hospital, Parkville, VIC 3052, Aus-tralia. E-mail: weintrar@cryptic.rch.unimelb.edu.au

Received 15 May 1998; Accepted 27 July 1998

American Journal of Medical Genetics 82:146–148 (1999)

© 1999 Wiley-Liss, Inc.

cyte studies were normal and a normal thymus wasfound at surgery. Karyotype analysis showed 46,XXwithout a 22q11.2 microdeletion. At 10 months of ageshe is well and does not have any appreciable aorticregurgitation.

Subsequent comparisons of DNA at multiple pointsfrom chromosomes 7, 8, and 15 were consistent withmonozygosity (Table I).

DISCUSSION

This case report describes monozygotic twins withPTA who did not have laboratory evidence of a 22q11microdeletion or clinical features of syndromes associ-ated with such a deletion. The most common identifi-able genetic cause of CTHM is a microdeletion of chro-mosome 22q11.2. Chromosomal deletions in the 22q11region are found in 76% of patients with the velocar-diofacial syndrome, 88% of those with DiGeorge syn-drome [Driscoll et al., 1993], and 84% of people withconotruncal anomaly face syndrome [Matsuoka et al.,1994]. The incidence of 22q11 deletions in patients

with isolated CTHM is controversial, with studies in-dicating variances between 0 and 30% [Debrus et al.,1996; Devriendt et al., 1996; Goldmuntz et al., 1993;Takahashi et al., 1995]. Conotruncal cardiac malforma-tions may occur in the genitopalatocardiac syndromeand Kousseff syndrome [McKusick, 1997].

The absence of a 22q11.2 microdeletion using asingle probe (in this case D22S75 Oncor) does not ab-solutely exclude a microdeletion in this region as theunderlying cause, as the deletion may not include theregion where this probe hybridizes but does make itvery unlikely. Whilst the cardiac malformations inthese sibs appear to be isolated, other features of syn-dromic causes, such as velopharyngeal incompetenceand dysmorphic facies in velocardiofacial syndrome,may only become apparent with increasing age. Dele-tions of chromosome 10p have been found in patientswith features of DiGeorge syndrome and velocardiofa-cial syndrome [Daw et al., 1996; Lipson et al., 1996;Schuffenhauer et al., 1995]. It is unclear whether chro-mosome 10p deletions underlie isolated conotruncalcardiac malformations.

The female first cousin with tetralogy of Fallot is ofinterest. Tetralogy of Fallot is relatively common (10%of congenital cardiac malformations [Park, 1988]),therefore this may be coincidental. Alternatively, itmay suggest that this family either has a dominantsingle-gene disorder with incomplete penetrance or apolygenic condition. Autosomal recessive inheritance isunlikely because of the absence of consanguinity be-tween III-6 and III-7, III-8 and III-9, as well as III-7and III-9 (Fig. 1). Another unlikely but intriguing pos-sibility is X-linked inheritance with male sparing,which has recently been reported in a family with fe-male members affected by epilepsy and mental retar-dation [Ryan et al., 1997].

Environmental causes also have been implicated inthe occurrence of CTHM. Parental cigarette smokingwas found to be associated in one study [Wasserman etal., 1996], whilst two studies found that periconceptual

Fig. 1. Pedigree of the family described.

TABLE I. DNA Analysis: 12 of the 30 Markers Examined inChromosomes 7, 8, and 15 Confirming the Monozygosity

Among the Twins

Marker

Allele a (base pairs) Allele b (base pairs)

Twin 1 Twin 2 Twin 1 Twin 2

D7S484 118 118 116 116D7S513 184 184 182 182D7S530 119 119 117 117D7S669 186 186 184 184D8S260 216 216 214 214D8S272 256 256 254 254D8S504 147 147 145 145D8S514 224 224 222 222D15S117 328 328 326 326D15S128 207 207 205 205D15S131 269 269 267 267D15S165 206 206 204 204

Persistent Truncus Arteriosus in Monozygotic Twins 147

multivitamin intake reduced the occurrence of CTMH[Botto et al., 1996; Shaw et al., 1995]. Animal studiesalso show that teratogens can induce CTHM[Kuribayashi and Roberts, 1993]. In the case describedthere was no historical evidence of teratogen exposure,but this possibility cannot be discounted.

ACKNOWLEDGMENT

Dr. Mas is partially supported by a grant from theCaja Costarricense de Seguro Social, San Jose, CostaRica.

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