Brit. Heart J., 1968, 30, 645.

Atrioventricular Defects-A Study of 92 FamiliesRICHARD EMANUEL, JANE NICHOLS, JANET M. ANDERS, ELIZABETH C. MOORES,

AND JANE SOMERVILLEFrom The Institute of Cardiology and National Heart Hospital, London W.], and The Middlesex Hospital, London W.1

There is no simple mode of inheritance in isolatedcongenital heart disease (Polani and Campbell,1955; Lamy, de Grouchy, and Schweisguth, 1957;McKusick, 1964; Campbell, 1965; Ehlers andEngle, 1966), though the high consanguinity indexin situs inversus, secundum atrial septal defect,pulmonary valve stenosis, persistent ductus arterio-sus, and ventricular septal defect suggests that arecessive gene may play a part in the production ofthese lesions (Campbell, 1965). The importanceof genetic factors, however, probably differs invarious forms of congenital heart disease, for insecundum atrial septal defects both the parentsand children of the propositi as well as the sibsare at increased risk, whereas with most other typesof congenital cardiac defects only the sibs are morefrequently affected than normal (Campbell, 1965).Chromosome analysis has not helped to elucidatethe pattern of inheritance, unless the presence ofmarker chromosomes is relevant. German, Ehlers,and Engle (1966) found these variants more fre-quently in familial cases of congenital heart diseasethan expected, but in our previous study, mainly ofnon-familial cases, the frequency of marker chromo-somes was similar to that in the general population(Anders, Moores, and Emanuel, 1965; Moores,Anders, and Emanuel, 1966).

Family studies have been reported in patientswith cardiomyopathy (Evans, 1949; Pare et al.,1961; Barry and Hall, 1962), persistent ductusarteriosus (Polani and Campbell, 1960), coarctationofthe aorta (Campbell and Polani, 1961a), secundumatrial septal defect (Campbell and Polani, 1961b;Zuckerman et al., 1962; Nora, McNamara, andClarke Fraser, 1967), pulmonary stenosis (Camp-bell, 1962), situs inversus (Campbell, 1963), con-genital aortic stenosis (Zoethout, Bonham-Carter,and Carter, 1964), and ventricular defect (Campbelland Goodwin, 1965).Received December 7, 1967.

Preliminary observations on a large series ofatrioventricular defects suggested that there mightbe an unusually high incidence of congenital lesionsin the heart and other systems in relatives of thepropositi (Somerville, 1966). In view of this, itwas decided to undertake a more detailed study.

TERMINOLOGYThe term atrioventricular defect, introduced by

Bedford et al. (1957), has been used to includepatients with ostium primum defect, common atrio-ventricular canal, and single atrium as previouslydescribed (Somerville, 1965).The term concordant has been used when both

propositus and relative have the same type of atrialseptal defect, but it does not exclude an additionalcongenital cardiac defect in either.

SUBJECTS AND METHODA total of 123 patients with atrioventricular defects

attended either the National Heart Hospital or Middle-sex Hospital between 1958 and 1965, and the families of92 of these were interviewed. The remaining 31 wereexcluded, as 10 could not be traced, 6 refused to help(the propositus in 4 of these had died), and 6 livedabroad. Three patients were adopted and no familydetails were available. Six patients with Down's syn-drome were also excluded.The 92 included 43 males (7 dead) and 49 females

(9 dead), a sex ratio of 1:1 1. The ages of the propositiranged from 2 to 70 years and the distribution is shownin Fig. 1. Two patients were related but were treatedas separate propositi as each had been independentlyreferred.

Diagnosis of the atrioventricular defect was confirmedby open heart surgery in 52 patients, cardiac catheteriza-tion and left ventricular angiography in 15, and necropsyin 5. In the remaining 20 an atrioventricular defect wasdiagnosed on the clinical evidence, together with thetypical electrocardiographic findings of left axis devia-tion. Cardiac catheterization confirmed a left-to-rightshunt at atrial level in all these patients.

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30-

25-

_r

0

Q.

0

z

20-

10-

5-

Dead

Living

. .

pre 1900 1910- 1930- 1950-90 1920- 1940- 1960-

Year of birth

FIG. 1. Age distribution of the 92 propositi.

The 92 families under review were composed of 433first degree relatives (184 parents, 229 sibs, and 20children of the propositi), 1160 second degree relatives(368 grandparents, 5 grandchildren, 606 uncles andaunts, and 181 nephews and nieces), and 1087 firstcousins. Information on more distant relatives withcardiac abnormalities was volunteered by a few families.The general practitioner of the propositus was con-

tacted and then an explanatory letter requesting aninterview was sent to each family. The family wasseen at home when possible. If the propositus couldnot be traced with the help of the general practitioneralone, the appropriate N.H.S. Executive Council wasapproached. At the interview a family pedigree was con-structed which included all first and second degreerelatives and first cousins and in only 8 families was thisinformation known to be incomplete. Questions werespecifically asked about heart disease as well as aboutskeletal and dental abnormalities. Prenatal details re-

TABLE IADDITIONAL CARDIAC MALFORMATIONS

IN PROPOSITI

Malformation No.

Secundum atrial septal defectSecundum atrial septal defect + partial anomalouspulmonary venous drainage

Secundum atrial septal defect + pulmonary stenosisSecundum atrial septal defect + left superior vena cavaVentricular septal defect in muscular septum + smallsecundum atrial septal defect

Pulmonary stenosisCoarctation of aortaAbnormal inferior vena cava draining into azygos systemComplete heart blockSino-atrial blockSitus inversusIsolated laevocardia + anomalies of systemic and pulmonaryvenous drainage

2

11

12

21

1

2

16

lating to the propositus were obtained from the motherwhenever possible.

All first degree relatives who were willing to co-operatewere examined clinically and had an electrocardiogramand chest radiograph. mitions were arrangedeither at the National Heart Hospital, Middlesex Hos-pital, or a convenient regional hospital. When informa-tion suggested that a second degree or more distantrelative might have congenital heart disease, detailswere sought from general practitioners, hospital records,death certificates, and necropsy reports.

In the analysis of stillbirth rates, maternal age, season

of birth, and birth order, the Registrar General's figureswere used for comparison. Stillbirth rates ofthe generalpopulation have only been recorded since 1930, and soall sibs born before then were excluded from the com-parative analysis. Similarly, as the figures relating tomaternal age, season of birth, and birth order haveonly been recorded since 1939, information from pro-positi born before this year was also excluded.

RESULTS

Malformations in Propositi. Congenital cardiaclesions in addition to the atrioventricular defectwere found in 16 (17 -4%) of the 92 propositi (TableI). Six of these patients had a secundum atrialseptal defect. Non-cardiac malformations, whichwere diagnosed on clinical rather than on radio-logical grounds, were predominantly skeletal andpresent in 39 (42-4%) of the propositi (Table II).

Malformations in First Degree Relatives. Con-genital heart disease was diagnosed in 8 (1 8%) ofthe 433 first degree relatives, who were made up of184 parents, 229 sibs, and 20 children.

TABLE II

NON-CARDIAC MALFORMATIONS IN PROPOSITI

Malformation No.

High arched palate 10High arched palate, kyphoscoliosis, arachnodactyly 2High arched palate, arachnodactyly 2High arched palate, prominent sternum 1High arched palate, scoliosis, torticollis 1High arched palate, brachycephaly 1High arched palate, bilateral congenital cataracts 1

Arachnodactyly 3Arachnodactyly, depressed sternum 1Arachnodactyly, depression of hemithorax 1

Chest deformity (unspecified) 3Pigeon chest 1Pigeon chest, bilateral Harrison sulcus 1

Scoliosis 1Dorsal kyphosis 1Multiple rib abnormalities 1Hypertelorism 2

Hypertelorism, brachycephaly 1Brachycephaly 1Polydactyly, webbing of hands 1Webbing (slight) of hands and feet 1Cleft palate 1Kiinfelter's syndrome 1

39

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TABLE IIICONGENITAL HEART DISEASE IN 26 RELATIVES OF PROPOSITI

Relation of Pedigree Method or sourcepropositus nuber Diagnosis of diagnosis

First degreeParents 57, I. 2 Complete congenital heart block Clinical investigation*

66, I. 1 Secundum atnal septal defect OperationSibs 3, I. 2 AV defect+ secundum atrial septal defect Operation

46, II. 4 Transposition of great vessels Necropsy59, I. 2 Secundum atrial septal defect Clinical investigation*66, II. 3 Secundum atrial septal defect Operation

Children 56, 11. 3 Secundum atrial septal defect Cardiac catheterization90, III. 1 Secundum atrial septal defect Cardiac catheterization

and angiocardiographySecond degree

Uncles 3, I. 3 AV defect+ pulmonary stenosis Operation47, 1. 4 Congenital heart disease Death certificate82, I. 4 Congenital mitral disease Death certificate

Aunts 36, I. 12 AV defect Cardiac catheterizationNephews 51, III. 1 AV defect NeaopsyNieces 34, III. 1 Ventricular septal defect Cronipal investigation*

56, III. 1 Patent foramen ovale Death certificate;no necropsy

84, III. 1 Pulmonary valve stenosis Clinical investigation*Thirddegree,

First cousins 34, I. 6 Persistent ductus arteriosus Operation59, II. 7 Persistent ductus arteriosus + patent Necropsy

foramen ovale59, II. 10 Fallot's tetralogy Necropsy76, II. 4 Eisenmenger's syndrome Death certificate

Others 7, III. 1 Anomalous left coronary artery Necropsy19, II. 3 Secundum atrial septal defect Operation33, IV. 1 Fallot's tetralogy Clinical investigation*33, IV. 2 Fallot's tetralogy -Cardiac catheterization

and angiocardiography47, III. 2 Persistent ductus arteriosus + patent Necropsy

foramen ovale53, III. 2 Persistent ductus arteriosus Operation

* Clinical investigation = physical exarnination, electrocardiography, and a chest radiograph.

There were 156 living parents, 111 (71 2%) ofwhom were examined. Two of these had con-genital heart disease: one a secundum atrial septaldefect and the other congenital heart block (TableIII). One other had a partial right bundle-branchblock, but there was no evidence of a septal defect.Of the 28 dead parents, 4 had died from unknowncauses, and in the remaining 24 there was nothing

to suggest any form of congenital heart disease.Congenital cardiac lesions were therefore presentin 2 (1 1%) of the 184 parents (Table IV). Non-cardiac malformations were found in 6 (3.3%) ofthe parents and included depressed sternum withdorsal scoliosis, pigeon chest, cleft palate with ac-cessory teeth, congenital absence of lateral incisorteeth, bilateral renal pelves and ureters, and leftaccessory nipple.There were 205 living sibs, 118 (57-6%) ofwhom

were examined. A secundum atrial septal defectwas found in 2 (Table III). A partial right bundle-branch block was present in 5 others but again therewas no evidence of a septal defect. There were24 dead sibs. One had an atrioventricular defectcomplicated by a secundum atrial septal defect andanother had transposition of the great arteries(Table III). Five others were stillborn and nofurther information was available. There wasnothing in the remaning 17 to suggest cgenital

heart disease. In all, therefore, 4 (1 -7%) of the229 sibs had congenital cardiac defects (Table IV).Non-cardiac malformations present in 10 (4.4%) ofthe sibs were mainly skeletal and included 4 casesof sternal depression and one case each of severescoliosis, bilateral cervical ribs, cleft palate, 4 ac-cessory teeth, congenital absence of lateral incisorteeth, and unilateral hydronephrosis.The propositi had 20 children. One was still-

born and 16 (84 2%) ofthe 19 living were examined.Secundum atrial septal defects were present in 2

TABLE IVRELATIVES WITH CONGENITAL HEART DISEASE

Numbers Per centwith with

Relatives Numbers* congenital congenitalheart heartdisease disease

Parents 184 2 1-1Sibs 229 4 1-7Children 20 2 10-0Grandparents 368 0 0 0Grandchildren 5 0 0.0Uncles and aunts 606 4 0 7Nephews and nieces 181 4 2-2First cousins 1087 4 0 4Others 0 6 0.0

* Numbers refer to the total number in each group and not to thenumber ezamined, so that the percentage with congenital heartdisease is min l in each instance.

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TABLE VMATERNAL AGE DISTRIBUTION OF 64 PROPOSITI BORN AFTER 1939 (p=0.7)

<20 20-24 25-29 30-34 35-39 40-44 45-49 50+ Total

Index cases 4 0 18-0 24-0 9 0 5 0 4 0 0.0 0.0 64-0General population 2 7 17 6 20-2 13 7 7 4 2-1 0.1 0.0 63*8

(10-0%) (Tables III and IV). A partial rightbundle-branch block was found in one. Onechild had a depressed sternum.

Malformations in Other Relatives. In this studyonly first degree relatives were examined, but con-genital heart disease had already been diagnosedwith reasonable certainty in 8 (0-7%) of the 1160second degree relatives, which included 4 (0-7%)of the 606 uncles and aunts and 4 (2 2%) of the181 nephews and nieces (Tables III and IV). Noneof the 368 grandparents or the 5 grandchildren wasknown to have cardiac defects. Congenital cardiacmalformations had also been diagnosed in 4 (0O4%)of the 1087 first cousins and in 6 more distant rela-tives (Table III), but in this group no idea of thefrequency could be obtained as there was no indica-tion of the total number of relatives concerned.Congenital heart disease was suspected in at least3 other second degree relatives and 2 first cousins,but they were excluded as there was insufficientevidence to confirm the diagnosis. Information re-lating to non-cardiac malformations was not con-

sidered sufficiently accurate to be included.

Consanguinity. There was no instance ofparentalconsanguinity. The paternal grandparents of onemale propositus were second cousins but there wereno other cases of congenital heart disease in thisfamily.

Twins. Six of the 92 propositi had a twin sib,which was significantly higher (p=0 05) than theexpected 1 in 40. Information was available on3 of the twins, none of whom had congenital heartdisease. Further details were as follows. Themale twins of 2 female propositi were dead: onewas stillborn and no further information was avail-able; the other, born prematurely, died aged 1 day,

and there was nothing to suggest congenital heartdisease though no necropsy was performed. Twomale propositi had normal twin brothers, both pairsreputedly being dizygotic. The twin sister of afemale propositus and the twin brother of a malepropositus refused to be examined; once again, bothpairs were said to be dizygotic though we have noproof.

Stillbirths. Three of the 150 sibs born from1930 onwards were stillborn which was close tothe expected figure of 3-9%.

Miscarriages. Information was obtained fromthe mothers of 65 propositi; 145 pregnancies werereported, 17 (11 7%) of which had ended in mis-carriage, a figure well within the accepted range of6-8 to 21 per cent quoted by Logan (1959).

Maternal Age. The age of the mothers of the64 propositi born from 1939 onwards was known.Table V shows that the distribution of maternalage was not significantly different from that of thegeneral population. The mean maternal age was27 9 years compared with the expected 28 5 years.

The age of all parents in the study is given in theAppendix.

Birth Order. The birth order distribution ofthe 64 propositi bom after 1939 was not significantlydifferent from normal (Table VI). The mean birthorder was 1-6 compared with the expected 1-7 andthe average family size was 3-5. The birth orderof all propositi is given in the Appendix.

Birthweight. Accurate information was avail-able on the birthweight of 31 male and 30 femalepropositi. The average was 3175 g. (7 0 lb.) foreach sex.

LE VIBIRTH ORDER DISTRIBUTION OF 64 PROPOSITI BORN AFTER 1939 (p=0 7)

0 1 2 3 4 5 6 7 8 9 10+ 15+ Total

Index cases 31-0 16-0 7-0 7 0 1-0 0.0 1-0 0.0 0.0 0.0 1-0 0.0 64-0General population 26*0 19*0 9*4 4*4 2*3 1 2 07 04 03 02 02 00 64 1

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Season of Birth. Births in the general popula-tion occur most often in the second quarter of theyear, followed, in descending order of frequency bythe first, third, and fourth quarters. The quarterlydistribution of births of 64 propositi born after1939 was first quarter 15, second quarter 20, thirdquarter 18, and fourth quarter 11. As expected,the highest and lowest incidences occurred in thesecond and fourth quarters, respectively. Al-though, contrary to expectation, slightly more pro-positi were born in the third than in the first quar-ter, there was no indication of a significant quarterlyvariation.

Pregnancy Events. Information was obtainedfrom 77 families. During the first trimester ofpregnancy 6 mothers had a threatened miscarriageand one suffered pelvic trauma following an accident.There was no history ofrubella or any other maternalinfection apart from 2 cases of mild pyelonephritis.

DISCUSSIONIn atrioventricular defects, as in other forms of

isolated congenital heart disease so far studied, nosingle mode of inheritance was evident. Therewas, however, a high familial incidence of congenitalheart disease as 18 (19 6%) of the 92 propositi hadone or more affected relatives (Fig. 2). Congenitalcardiac defects were found more frequently than theexpected 0-6 per cent in parents (11%), sibs (1 -7%),children (10%), uncles and aunts (0-7%), andnephews and nieces (2-2%). As these figures arerelated to the total number in each group and notto the numbers examined, it is quite possible thatthe percentages might have been higher if all rela-tions in each group had been examined. The pat-tern of inheritance in atrioventricular defect wastherefore similar to that in secundum atrial septaldefect (Campbell and Polani, 1961b; Nora et al.,1967) but dissimilar to other forms of congenitalheart disease where only the sibs of the propositiwere at increased risk (Campbell, 1965).There were 26 cases of congenital heart disease

among the relatives of the index cases (Table III).The cardiac defect was similar (concordant) to thatof the propositus in only 4 (Pedigree 3, 36, and 51see Appendix) and was dissimilar (discordant) in22, but this included 6 cases of secundum atrialseptal defect. There appears, therefore, to be anassociation between atrioventricular defect andsecundum atrial septal defect which is again sug-gested by the coexistence of the two lesions in 6(10.5%) of the 57 propositi in whom the septumwas examined either at open heart surgery or atnecropsy. This association is not surprising inview of the interdependence of the septum primum

and septum secundum in the development of thefinal atrial septum (Somerville, 1966).

In their study of secundum atrial septal defectNora et al. (1967) found a familial incidence of 32per cent which is much higher than our figure of19-6 per cent for atrioventricular defects. Simi-larly, there was a much higher incidence of con-cordant lesions amongst first degree relatives, 15out of 17 cases, compared with one out of 8 inatrioventricular defects; these findings suggest thatgenetic factors are more important in secundumatrial septal defects than in atrioventricular defects.Further support for this concept comes from thehigh consanguinity index in secundum atrial septaldefect (Campbell, 1965) compared to the absence ofparental consanguinity in atrioventricular defects.The high frequency of twin births among the

propositi was unexpected and remained unexplained.This association has not been noted in other formsof congenital heart disease.

Maternal age, birth order, and season of birthdid not appear to have any significance in atrio-ventricular defects, and nothing suggested thatrubella or any other maternal infection duringpregnancy played a part. There was nothing toindicate that factors causing stillbirth or miscarriagewere relevant, as the number of pregnancies endingin foetal death or stillbirth was no higher thannormal. In the propositi there was a high inci-dence (42.4%) of associated congenital abnormali-ties which were mainly skeletal, but in the rela-tives, data on abnormalities outside the cardiovas-cular system were inadequate for analysis.

SUMMARYThe families of 92 cases of atrioventricular defect

were studied and the first degree relatives examinedwhenever possible.

Eighteen (19X6%) of the 92 propositi had one ormore relatives with congenital heart disease; only3 of these, however, had relatives (4 cases) withconcordant lesions.

Sixteen (17X4%) of the propositi had additionalcardiac malformations, 6 of which were secundumatrial septal defects.

Thirty-nine (42-4%) of the propositi had non-cardiac malformations which were mainly skeletal.

In the first degree relatives, 2 (1 1%) of the 184parents, 4 (1-7%) of the 229 sibs, and 2 (10 0%) ofthe 20 children had congenital heart disease. Inonly 1 of the 8 cases was the lesion concordant.There were, however, 5 cases of secundum atrialseptal defect.

In the second degree relatives, 4 (0-7%) of the606 uncles and aunts and 4 (2.2%) of the 181nephews and nieces had congenital heart disease.

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None of the 368 grandparents or 5 grandchildrenwas thought to be affected. Three of the 8 lesionswere concordant and there was no case of secundumatrial septal defect in the remaining 5.

In the 1087 first cousins, 4 (0-4%) had congenitalheart disease. None had an atrioventricular de-fect or secundum atrial septal defect.

In the more distant relatives, there were 6 cases

of congenital heart disease. The lesions, whichincluded one secundum atrial septal defect, werediscordant.There was no instance of consanguinity be-

tween parents of the propositi. The paternal grand-parents of qne propositus were second cousins.

Six of the 92 propositi had a twin sib, which ishigher than the expected one in 40.

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Mothers of propositi had no more miscarriagesand stillbirths than would be expected.

Maternal age, season of birth, birth order, andmaternal infection during the first trimester ofpregnancy did not appear to be relevant factors inatrioventricular defect.

We again express our gratitude to the NuffieldFoundation for their support of the Genetics Laboratoryat the Institute of Cardiology, and to Mr. F. Le NeveFoster for financial help and personal interest.We are greatly indebted to Dr. C. 0. Carter and Mrs.

K. Evans at the Institute of Child Health and to Mr.R. Withers, of the Biology Department of The Middle-sex Hospital Medical School, for help in many facetsof this work.We should also like to thank the consultants and

general practitioners throughout the country who havecollected information for us and arranged for theexamination of relatives, and without whose help thiswork would not have been possible.

REFERENCES

Anders, J. M., Moores, E. C., and Emanuel, R. (1965).Chromosome studies in 156 patients with congenitalheart disease. Brit. Heart_J., 27, 756.

Barry, M., and Hall, M. (1962). Familial cardiomyopathy.Brit. Heart J., 24, 613.

Bedford, D. E., Sellors, T. H., Somerville, W., Belcher, J. R.,and Besterman, E. M. M. (1957). Atrial septal defectand its surgical treatment. Lancet, 1, 1255.

Campbell, M. (1962). Factors in the aetiology of pulmonarystenosis. Brit. Heart J., 24, 625.(1963). The mode of inheritance in isolated laevocardiaand dextrocardia and situs inversus. Brit. Heart J.,

25, 803.(1965). Causes of malformations of the heart. Brit.med. J., 2, 895.

, and Goodwin, J. (1965). Some factors in the etiologyof ventricular septal defect. Progr. cardiovasc. Dis.,7, 417.

, and Polani, P. E. (1961a). The aetiology of coarctationof the aorta. Lancet, 1, 463.

, and (1961b). Factors in the aetiology of atrialseptal defect. Brit. Heart3j., 23, 477.

Ehlers, K. H., and Engle, M. A. (1966). Familial congenitalheart disease. I. Genetic and environmental factors.Circulation, 34, 503.

Evans, W. (1949). Familial cardiomegaly. Brit. Heart J.

11, 68.German, J., Ehlers, K. H., and Engle, M. A. (1966). Fami-

lial congenital heart disease. II. Chromosomal studies.Circulation, 34, 517.

Lamy, M., de Grouchy, J., and Schweisguth, 0. (1957).Genetic and non-genetic factors in the etiology of con-

genital heart disease: a study of 1188 cases. Amer.J.

hum. Genet., 9, 17.Logan, W. P. D. (1959). Vital statistics of reproduction.

In British Obstetric and Gynaecological Practice, 2nd ed.,Vol.2: Obstetrics, p. 1195. Ed. byE. Holland. Heine-mann, London.

McKusick, V. A. (1964). A genetical view of cardiovasculardisease. Circulation, 30, 326.

Moores, E. C., Anders, J. M., and Emanuel, R. (1966).Inheritance of marker chromosomes from a cytogeneticsurvey of congenital heart disease. Ann. hum. Genet.,30, 77.

Nora, J. J., McNamara, D. G., and Clarke Fraser, F. (1967).Hereditary factors in atrial septal defect. Circulation,35, 448.

Pare, J. A. P., Fraser, R. G., Pirozynski, W. J., Shanks, J. A.,and Stubington, D. (1961). Hereditary cardiovasculardysplasia. A form of familial cardiomyopathy. Amer.J. Med., 31, 37.

Polani, P. E., and Campbell, M. (1955). An aetiologicalstudy of congenital heart disease. Ann. hum. Genet.,19, 209.

,and (1960). Factors in the causation of persistentductus arteriosus. Ann. hum. Genet., 24, 343.

Somerville, J. (1965). Ostium primum defect: factors causingdeterioration in the natural history. Brit. Heart J.,

27, 413.(1966). Atrioventricular defects. M.D. Thesis, Univ-ersity of London.

Zoethout, H. E., Bonham-Carter, R. E., and Carter, C. 0.

(1964). A family study of aortic stenosis. J. med.Genet., 1, 2.

Zuckerman, H. S., Zuckerman, G. H., Mammen, R. E., andWassermil, M. (1962). Atrial septal defect. Familialoccurrence in four generations of one family. Amer.J7. Cardiol., 9, 515.

APPENDIX-overleaf

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APPENDIXSIBSHIPS OF INDEX PATIENTS WITH ATRIOVENTRICULAR DEFECTS

Propositi are in italics, relatives with congenital heart disease are marked t, relatives examined but unaffected are marked *; M = male;F = female; m = miacarriage; SB = atillbirth; d = died; - = not known; twina are in aquare brackets.

Serial Date of birth (month and BirthweightNo. year) of

Propositus, date of birth, and sibship propositiChildren Mother IFather (g.)

1 M 6.59; F*4.61; M*9.63 10.30* 10.36* 38562 M4 7.36 - --(d) -

3 M 1.44; Ft 9.45(d); M 9.48 12.14* 1.08(d) 36294 M 1.35; M 11.38; M 9.46 M--(SB) 12.14 11.12 30625 [F-(d); F--(d)]; M 8.29; M 12.30; [M 1.32; M 1.32]; F 10.36; F 3.41; F 11.45 12.98* 8.99* -

6 M 3.50(d 7.57) M* 4.51; M* 8.57; in-; F* 10.60; F* 10.62 1.28* 5.14* 29497 M* 1.62; M 4. 3(d); M* 6.64; F* 8.65 12.43* 3.36 34028 M 12.40; M 3.46; F 1.48; M 5.52; in-; F 1.57 11.20 11.16 -

9 M9.49; F* 6.51 3.13* 11.15* 294910 F 10.39; F* 12.42; in-; M 6.44; F* 2.57 9.19* 9.16* 232411 M 12.05; M 12.07; M 6.12(d); F 5.17 3.78 11.81(d) -12 F 8.39; M* 3.42; M* 11.43; M 3.53 4.14* 12.11* -13 M 7.49 12.28 7.21 362914 M 1.64;M8.65 10.42 12.42 303315 F* 3.56; F* 9.57; M 2.61(d) 8.37* 2.33* 289216 m 10.51; [M 5.53; M* 5.53]; F* 9.65 11.28* 12.26* 311817 F* 1.48; F* 5.50; M* 8.56; M 3.59 3.30* 3.22* 340218 F 1.08;M 11.09; F* 5.11; F 11.13; F 7.15;M -(d); F 2.19;M 11.29 1.89 -.83(d) -

19 M* 1.48; M 3.50; F* 11.55 6.26* 1.30* 317520 M 7.52; F* 5.55 7.20* 10.12* 289221 M 3.51 10.27* 6.23* 362922 M 1900(d); F -; M 4.05; F -(d) M 1.32 -(d) -(d) -

23 m 3.55;M 2.58 8.27* 5.27* 377124 F* 8.38; M 4.40; F* 3.52 8.09* -.05* 238125 F 4.55; (M 5.59; M 5.59] M* 10.63; 4.31 1.31 2949

M* 11.6526 M-06;M-08;F-10;M-;M-.;F-;M-;M-;F-;F- .80(d) --(d) -

M 12.24; F --(d)27 F* 8.57; M* 1.59; M* 5.60; F* 7.61; M 9.62; F* 5.64; M* 9.65 8.37 3.34 377128 F 10.37; M 5.42(d) 8.01* 3.05* 280729 M* 8.41;M 11.42 5.14* 4.15(d) -

30 M 3.57; F* 4.62; F* 2.64 3.28* 3.29* 283531 M 9.46; M* 12.47; M 2.50; M* 9.55 -20(d) 12.20* 377132 F* -06; F* -10; M 8.12; M 5.18 .88(d) .85-33 [Ml 2.57; M* 2.57] 3.26* 5.20* 141834 F 3.44; M* 10.45; F* 11.46; Ml 6.48(d);m-8.24* 4.24* 317535 Ml 5.37; M* 10.38 7.15* 9.05* 209736 M 7.52(d); F* 8.55; M* 3.58 2.30* 3.27* 283537 Ml 8.54; M 12.55 6.29 8.28 286338 Ml 7.59; m -; M* 10.60; F* 7.62; m-7.40 1.36 317539 M* -; Ml 10.24; [M* -; F*-]F* ~- -(d) -

40 Al 1.39(d); F 4.45 2.15* 3.15* 368641 F* 8.53; F* 6.56; Ml12.58 5.29* 3.30* 374242 M* 7.51; Al 9.52; F* 10.58 10.29* 3.29* 362943 Al 12.29; M 8.36; M 5.39; M 8.44 11.06 9.96 -

44 P 10.39; F 8.43 10.13 5.11 -

45 F 3.56; M* 12.59 3.33* 6.31* 275046 M 10.46; P 5.49; F* 1.57; Mt 10.61(d) 12.20* 11.13 368647 P 9.45(d. 11.61); F 6.50(d). i3.19 10.12 340248 P 9.45(d); F* 10.47 1.25* 7.24 292049 P6.45;m-;m- 7.24* 6.20 -

50 M* 6.56; F 11.57; M* 2.62 1.31* 6.23* 331751 M 9.14; F* 1.16; F* 3.19; F 9.21; F 4.25; M 9.26; F 3.28; F* 2.30; M 4.33;

F 7.34; F 5.39 F* 12.58 5.95* 2.90(d) 317552 M* 10.54; P 4.56; [M* 7.58; F* 7.58] 6.30* 6.30* 249553 F 10.39 M* 11.65 7.15* 9.10* 396954 P 4.48 6.18 10.18 272255 P 3.96; M 7.97; F --(d); M -; M -; M--(d) --(d) --(d) -

56 F -(d); M -91(d); F --93; F -96; [P 11.04; M 11.04(SB)] F* 2.31; --(d) -{(d) -Mt 11.32;M* 3.40;M* 5.47

57 P 5.30(d); M* 4.36 1.07t 1.02(d) -58 F 5.40; M* 11.41; F* 5.54; P 8.60 11.16* 11.09(d) -59 P 4.44(d); Ft 2.48; M* 8.62 2.20* 11.17* 229660 F 3.30; P 5.33; F* 6.34; F* 7.46 7.06* 9.96* 283561 F* 7.46; M* 9.49; F 11.60; F 2.63(SB) 10.22* 11.13* 388462 P 10.47; M 11.50 2.27 11.25* -63 F 10.30; F 7.33; M 5.36; M 10.39; F 9.44; F 6.47; P 7.48 3.05(d) 5.06(d) -64 [P 11.49; M 11.49(d)] 3.13* 5.14* 113465 m -43; F* 7.44; m -46; F* 8.47; F* 10.48; P 7.50; M* 5.52; F* 9.53;

F* 9.56; [F* 2.58; M 2.58(SB)]; F* 5.62 10.23* 5.23* 229666 P 8.37(d); M* 12.44; M*t 8.46 8.11* 9.08t 442267 F* 1.29; F 3.37 M* 10.60; 4.10* 5.03 -

M* 6.6268 M* 7.36; P 1.43 10.12* 4.13* -

69 P4.48;m- 1.20* 6.17* 340270 M* 5.53;PF6.56 2.28* 12.28* 357171 P 2.48; M* 12.49; F* 9.57 11.21* 2.20* -72 F* 5.41;PF8.46 7.18* 2.16* -73 P 6.47 4.28* 7.25 430974 M 12.38; F* 2.44; m -; P 12.45; F* 5.49; F* 8.53; M* 5.55; m -;F* 12.59 5.18* 6.18 3175

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Atrioventricular Defects-a Study of 92 Fanmlies

APPENDIX-continued

Serial Date of birth (month and BirthweightNo. year of

Propositus, date of birth, and sibship propositiChildren Mother Father (g.)

75 F* 3.54; F 8.58 4.30* 8.29* 241076 F 7.40; F 8.42; M* 8.52 F* 8.61; 12.19* 11.13* -

F* 10.6277 F 11.38; F* 7.40 12.06* 6.08* 331778 P 1.42 1.05* 8.09* -

79 M* 6.51;F 4.53 10.21* 12.21* 408280 [F 11.56(d. 2.65); F 11.56]; [M 3.60; F 3.60] 5.29 8.21 257981 M* 2.14; M* 7.15; P 9.17; [M 11.19(d); M* 11.19] -84* -(d) -

82 F* 9.47; M 9.51(SB); F 11.52 (d); F* 1.59 2.22* 6.19* 320383 M 1.37; P 8.39(d) 3.12 2.07 371484 M* 5.29; F* 9.33; F* 2.36; m -38; F 9.41; F* 2.43; M* 3.45 5.07* 7.04* 272285 M 7.34; M 9.37; M 12.38; F 8.42; F 6.48; F 8.49; M 1.52 M 8.63; 1.14 4.13 -

F 4.6586 F 1.04; M 7.07; F 9.09(d); F 9.10; F 1.13; M -17(d) -85(d) -(d) -

87 F 7.53; m -; F* 10.59 8.28* 8.28* 306288 M-08(SB); F* 1.09; F 7.10; M* 9.11; F* 2.13; m-; F* 3.14; M* 10.19;

M* 2.24- 8.84 6.82(d) -

89 F 10.33 m-62; - -(d) -

F* 8.6490 F* 6.35; F 3.36 Ft 1.61; 8.10 3.92* 3402

M* 5.6291 M 6.17; F 2.20; F 3.21; F 3.25 -91(d) 6.89(d) -

92 F 4.46; F 7.47; M 4.49 5.29* 12.23* 2949

653

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