- Email: [email protected]
SIMILAR CONGENITAL HEART DISEASE IN SIBLINGS
SIMILAR CONGENITAL HEART DISEASE I N SIBLINGS Fred K. Christensen, B.S.,* and Russell M. Nelson, M.D., Ph.D., Salt Lake City, Utah
I
in the possible etiological factors concerned with congenital heart disease has increased with the realization of the relatively high incidence of cardiovascular malformations at birth (0.83 per cent) 1 ' 2 and with the availability of surgical repair. It is well known that rubella during the first trimester of pregnancy may be a factor in some cases; however, the vast majority of children with congenital heart disease are products of apparently uneventful pregnancies with respect to disease of the mother. 3 ' 4 Congenital cardiac lesions apparently occur with increased frequency in families in which one such defect has already appeared. 5 Some cases are known to occur as part of a syndrome with determined genetic background, such as mongolism, 6 ' 7 Turner's syndrome, situs inversus, 8 Marfan's syndrome, 9 and Ehlers-Danlos syndrome.10 Studies of monozygous twins, in contrast, show only occasional affliction of both the twins. 11-14 "We have studied 13 families in which congenital heart disease has occurred in more than one sibling. These patients were numbered among a series of approximately 1,100 patients who have been subjected to heart catheterization for possible congenital heart disease. The purpose of this report is to present findings relative to these 13 families. NTEREST
METHODS AND PROCEDURE
1. Records of siblings afflicted with congenital heart disease were studied to ascertain the nature and possible similiarity of the lesion. 2. A detailed family history was obtained on each of these families to detect possible incidence of congenital heart disease in additional members of the family. 3. Family histories were obtained on 100 hospital persons selected at random for use as comparison. These were selected from consecutive noncardiac hospital admissions of pediatric age group during one month. 4. Palm prints were obtained, where possible, from the members of families with afflicted siblings. These were analyzed for characteristic dermatoglyphic From the Departments of Surgery, Salt Lake Clinic, Latter-day Saints Hospital, University of Utah College of Medicine, Salt Lake City, Utah. Supported by grants from the National Foundation, U. S. Public Health Service, American Heart Association, and the Utah Heart Association. Received for publication Sept. 27, 1962. •Medical Student Fellow of the National Foundation.
592
Vol. 45, No. 5 May, 1963
593
CONGENITAL H E A E T D I S E A S E I N SIBLINGS TABLE I
NO. OF SIBLING PAIES
N O . OF PAIKS I N W H I C H LESION W A S IDENTICAL
NO. OF PAIRS I N W H I C H LESION W A S SIMILAR
NO. OF PAIRS I N W H I C H LESION W A S DIFFERENT
Atrial septal defect Ventricular septal defect Valvular pulmonary stenosis Incomplete endocardial cushion defect (ostium primum with cleft mitral leaflet)
2
2
0
0
Tetralogy of Fallot
2
2
0
0
Semilunar valve stenosis (one aortic, one pulmonary) Patent ductus arteriosus
1 1
0 0
1 1
0 0
Totals
13
features, as reported in congenital heart disease by Hale. 15 These stigmata consist of the distal or multiple occurrence of the palmar axial triradius. To select families for the study, the records of various cardiac specialists* were studied for cases in which siblings were involved. All individuals were included in whom the cardiac abnormality was clearly congenital, regardless of the nature of the lesion. Thirteen such families were found. The nature of the cardiac lesion was confirmed by operative data in twelve of the pairs of siblings and by electrocardiogram, roentgenogram, and clinical manifestations in the remaining pair. Positive additional incidence of congenital heart disease in the family was reported, in all but one case, only if autopsy or operative data proved the diagnosis. The only other case in which an additional member of the family was listed as having congenital heart disease was reported on the basis of undisputable clinical evidence following the progress of the child up to death as a result of his heart condition. Suspected additional family incidence was reported on the basis of clinical findings only where the diagnosis was not proved. Negative reports were declared if the families, when questioned, were not aware of other relatives with congenital heart problems. I t is realized that this does not exclude the possibility of additional congenital heart defects existing in these families. RESULTS
Eesults of each section of the study are tabulated in the following tables. 1. Nature and Similiarity of Lesions in Siblings With Congenital Heart Disease. In 9 of the 13 families reported, the lesions of related afflicted siblings were identical, and, in 4 pairs of siblings, the lesions were similar. Nine of the sib* Gratitude is expressed to Drs. H. H. Hecht, L. B. Viko, JD Mortensen, R, J. Beveridge, L. G. Veasy, H. R. Warner, and A. F. Toronto for their cooperation in this study,
CHBISTENSEN AND NELSON
594
J. Thoracic and Cardiovas. Surg.
FAMILY A
o-
o
•n
o-
2
-D 4
0
3 other
3
normal children 1, Atrial septal defect with valvular pulmonary stenosis (operative findings). 2, Atrial septal defect with valvular pulmonary stenosis (operative findings). 3, Atrial septal defect with valvular pulmonary stenosis (clinical work-up including chest roentgenogram and electrocardiogram). No catheterization studies. b, Ventricular septal defect (operative findings).
FAMILY
B 6 others with no known defect
-•
□-
l
1
3 other normal 4 children 1, Ventricular septal defect (based on clinical data). No catheterization studies at present. 2, Ventricular septal defect (based on autopsy report). 3t Incomplete endocardial cushion defect (clinical data only). !f, Incomplete endocardial cushion defect (clinical data only).
u
FAMILY C
o
I
•
1□
1
i
n
n
o
1 o
1
1
o 1 o
i
1
•
n
1
1
•
2
O
1 o
1 c
o
3 1, Incomplete endocardial cushion defect (operative findings). 2, Incomplete endocardial cushion defect (operative findings). S, Ventricular septal defect (operative findings).
ling pairs were of the same sex while 3 were of opposite sex. The sex relationship of the remaining family in which all the siblings were afflicted is diagrammed under Family E. One pair of the afflicted siblings with identical lesions were twins, and, in another family, one of the afflicted siblings had a monozygous twin with a normal heart. 2. Incidence of Congenital Heart Disease in Additional Members of Families. Table I I demonstrates the results with respect to the possible incidence of congenital heart disease in additional members of families of the afflicted siblings.
Vol. 45. No. 5 May, 1963
CONGENITAL H E A R T D I S E A S E I N SIBLINGS
FAMILY D
□
•
1
595
O
•
■
□
1 2 3 /, Tetralogy of Fallot (operative findings). 2, Tetralogy of Fallot (operative findings). S, Exact nature of lesion undetermined. Patient died at age 1 of cyanotic heart disease (no autopsy). FAMILY E
. . . i
/, 2, 8, 4, 5,
2 3 4 Patent ductus arteriosus (operative findings). Aortic atresia (autopsy d a t a ) . Atrial septal defect, dextrocardia, patent ductus? (catheterization data). Patent ductus arteriosus (operative findings). Patent ductus arteriosus (clinical findings).
TABLE I I .
ADDITIONAL F A M I L Y INCIDENCE OF CONGENITAL
HEART DISEASE
ADDITIONAL FAMILY HISTORY LESION OF SIBLINGS
|
POSITIVE
Atrial septal defect
(4)
1*
Ventricular septal defect
SUSPECTED
|
NEGATIVE
1
2
(2)
0
1
1
Valvular pulmonary stenosis
(1)
0
0
1
Incomplete endocardial cushion defect (ostium primum with cleft mitral leaflet)
(2)
2tt
0
0
0
1
0 0
1 0
2
6
Tetralogy of Fallot
(2)
1§
Semilunar valve stenosis (one aortic, one pulmonary) Patent ductus arteriosus
(1) (1)
0
Totals •See diagram tSee diagram JSee diagram §See diagram || See diagram
111
■
5 of of of of of
Family Family Family Family Family
B. A. C. C. B.
3. Family Histories of 100 Unselected (Non-cardiac) Hospital Admissions. Results of the family histories of the 100 hospitalized persons used as a control are reported in Table I I I . TABLE
III
LESION
POSITIVE
SUSPECTED
NEGATIVE
Any congenital cardiac lesion
4
3
93
C H E I S T E N S E N AND N E L S O N
596
J. Thoracic and Cardiovas. Surg.
Fig. 1.—Usual placement of axial triradius. Pig-. 2.-—Distal placement of axial triradius characteristic of patients with congenital heart disease.
In 4 per cent of the 100 families interviewed there was an awareness of congenital heart disease. This compares with 38 per cent of the 13 sibling families in which congenital heart disease was confirmed. 4. Dermatoglyphic Studies Of 15 patients with congenital heart disease available for study, 11 have dermatoglyphic stigmata (73 per cent). Of 25 without heart disease, 6 have these stigmata (24 per cent). The standard error of the difference is 15 per cent, whereas the actual difference is nearly 50 per cent. These results are similar to those reported by Hale.* 15 The dermatoglyphic stigmata associated with congenital heart disease were not found in nonafflieted members of these families with any greater frequency than in the general population. DISCUSSION
There have been many isolated reports of siblings with similar congenital heart disease. McKeown,16 in reporting a group of 5 afflicted siblings, noted that 3 of the 5 sibling pairs had identical lesions. In analyzing the data of Chelius who reported 19 cases of congenital heart disease with a family incidence, it is apparent that 4 of the 10 cases occurring in these siblings had identical lesions.17 Considering the possibility of hereditary factors, Nadas has reported that, from a series of 2,500 patients with congenital heart disease, 15 families each had two siblings with a congenital heart lesion. He further ob*Gratitude is expressed to Dr. Alfred K. Hale of New Orleans for reviewing the palmar dermatoglyphics collected from these families.
y,0'- 4 ?AM°-
5
CONGENITAL HEART D I S E A S E I N SIBLINGS
5Q7
served that the same lesions were likely to be repeated in siblings of the same sex.18 In comparison, the study reported herewith includes 13 sibling pairs, 9 of which had identical lesions. Lesions were reported as similar, rather than identical, if one of the siblings had associated cardiac pathologic conditions not found in the other sibling. For example, if one sibling had an atrial septal defect and the other had atrial septal defect with an additional associated ventricular septal defect, the lesion was reported as similar, but not identical. One problem encountered in this study was that of detecting additional congenital heart malformations in the sibling families. It was the awareness of an additional family incidence rather than an actual additional family incidence that has been measured. Kauch, in a study of 85,389 school children (ages 5-19) to determine frequency of cardiac problems, reported that 24 per cent of the children discovered with congenital heart disease were totally unaware of the existence of these lesions previous to the examination. 19 Therefore, results from the methods we have used will not be as high as the true incidence of congenital heart disease. An attempt at arriving at a frame of reference was made by doing a control study of 100 families using the same technique and criterion as was used for the sibling families. The existence of one pair of identical twins, one with a congenital heart condition and the other with a normal heart, coincides with other such reports.11"14 This would suggest that etiology of congenital heart disease is not, therefore, a simple genetic factor. However, the frequency with which identical and similar lesions were found in families would indicate that familial factors may play a role. SUMMARY
Thirteen pairs of siblings with congenital heart disease have been studied. In 9 of these sibling pairs, the cardiac lesion was identical, and, in 4 of the pairs, the lesion of the related siblings was similar. Additional family incidence of congenital heart disease was confirmed in 5 of these 13 families. Associated dermatoglyphic stigmata were present in 73 per cent of patients with congenital heart disease compared to 24 per cent of their nonafflicted relatives. I t is concluded that familial factors may be related to the etiology of congenital heart disease. REFERENCES 1. Eichards, M. R., Merritt, K. K., Samuels, M. H., and Langman, A. G.: Congenital Malformations of the Cardiovascular System in a Series of 6,053 Infants, Pediatrics 16: 12, 1955. 2. Adams, F . H . : Congenital Heart Disease: Comments Regarding Incidence and Natural History, California Med. 90: 213, 1959. 3. Dogramaci, I., and Green, H . : Factors in the Etiology of Congenital Heart Anomalies, J . Pediat. 30: 295, 1947. 4. Miller, H. D.: Relation of Maternal Infection to Congenital Malformations of Heart, Mod. Concepts Cardiovas. Dis. 17: 27, 1948. 5. Carleton, R. A., Abelman, W. H., and Hancock, E. W.: Familial Occurrence of Congenital Heart Disease, New England J . Med. 259: 1237, 1958. 6. Annotations: Hereditary and Congenital Heart Disease, Brit. M. J . 1: 704, 1959. 7. Berg, J . M., Crome, L., and France, N . E . : Congenital Cardiac Malformations in Mongolism, Brit. H e a r t J . 22: 331, 1960.
598
C H E I S T E N S E N AND NELSON
J. Thoracic and
Cardiovas. Surg.
8. Campbell, M.: The Genetics of Congenital Heart Disease and Situs Inversus in Siblings, Brit. Heart J . 2 1 : 65, 1959. 9. McKusick, V. A.: The Cardiovascular Aspect of Marfan's Syndrome, Circulation 11: 321, 1955. 10. Freeman, J. T.: Ehlers-Danlos Syndrome, A. M. A. Am. J . Dis. Child. 79: 1049, 1950. 11. Benesova, P . , and Sikl, H . : A Rare Concordant Malformation in Monochoriate Twins, J . Path. & Bact. 67: 367, 1954. 12. Eoss, L. J . : Congenital Cardiovascular Anomalies in Twins, Circulation 20: 327, 1959. 13. Paes, O. de O.: Congenital Cyanotic Heart Disease in One of Monozygotic Twins, Am. Heart J . 52: 929, 1956. 14. Uchida, I . A., and Eowe, E. D . : Discordant Heart Anomalies in Twins, Am. J. Human Genet. 9: 122, 1957. 15. Hale, A. E., Phillips, J . H., and Burch, G. E . : Features of Palmar Dermatoglyphies in Congenital Heart Disease, J . A. M. A. 176: 41, 1961. 16. McKeown, T.: Familial Incidence of Congenital Malformation of Heart, Brit. Heart J . 15: 273, 1953. 17. Chelius, C. J., Eowe, G. G., and Crumpton, C. W.: Familial Aspects of Congenital Heart Disease, Am. J . Cardiol. 9: 508, 1962. 18. Nadas, A. S.: Pediatric Cardiology, Philadelphia, 1957, W. B. Saunders Company, p. 268. 19. Eauch, L. W.: The Incidence of Organic Heart Disease in Children, Am. Heart J. 18: 705, 1939.
I
in the possible etiological factors concerned with congenital heart disease has increased with the realization of the relatively high incidence of cardiovascular malformations at birth (0.83 per cent) 1 ' 2 and with the availability of surgical repair. It is well known that rubella during the first trimester of pregnancy may be a factor in some cases; however, the vast majority of children with congenital heart disease are products of apparently uneventful pregnancies with respect to disease of the mother. 3 ' 4 Congenital cardiac lesions apparently occur with increased frequency in families in which one such defect has already appeared. 5 Some cases are known to occur as part of a syndrome with determined genetic background, such as mongolism, 6 ' 7 Turner's syndrome, situs inversus, 8 Marfan's syndrome, 9 and Ehlers-Danlos syndrome.10 Studies of monozygous twins, in contrast, show only occasional affliction of both the twins. 11-14 "We have studied 13 families in which congenital heart disease has occurred in more than one sibling. These patients were numbered among a series of approximately 1,100 patients who have been subjected to heart catheterization for possible congenital heart disease. The purpose of this report is to present findings relative to these 13 families. NTEREST
METHODS AND PROCEDURE
1. Records of siblings afflicted with congenital heart disease were studied to ascertain the nature and possible similiarity of the lesion. 2. A detailed family history was obtained on each of these families to detect possible incidence of congenital heart disease in additional members of the family. 3. Family histories were obtained on 100 hospital persons selected at random for use as comparison. These were selected from consecutive noncardiac hospital admissions of pediatric age group during one month. 4. Palm prints were obtained, where possible, from the members of families with afflicted siblings. These were analyzed for characteristic dermatoglyphic From the Departments of Surgery, Salt Lake Clinic, Latter-day Saints Hospital, University of Utah College of Medicine, Salt Lake City, Utah. Supported by grants from the National Foundation, U. S. Public Health Service, American Heart Association, and the Utah Heart Association. Received for publication Sept. 27, 1962. •Medical Student Fellow of the National Foundation.
592
Vol. 45, No. 5 May, 1963
593
CONGENITAL H E A E T D I S E A S E I N SIBLINGS TABLE I
NO. OF SIBLING PAIES
N O . OF PAIKS I N W H I C H LESION W A S IDENTICAL
NO. OF PAIRS I N W H I C H LESION W A S SIMILAR
NO. OF PAIRS I N W H I C H LESION W A S DIFFERENT
Atrial septal defect Ventricular septal defect Valvular pulmonary stenosis Incomplete endocardial cushion defect (ostium primum with cleft mitral leaflet)
2
2
0
0
Tetralogy of Fallot
2
2
0
0
Semilunar valve stenosis (one aortic, one pulmonary) Patent ductus arteriosus
1 1
0 0
1 1
0 0
Totals
13
features, as reported in congenital heart disease by Hale. 15 These stigmata consist of the distal or multiple occurrence of the palmar axial triradius. To select families for the study, the records of various cardiac specialists* were studied for cases in which siblings were involved. All individuals were included in whom the cardiac abnormality was clearly congenital, regardless of the nature of the lesion. Thirteen such families were found. The nature of the cardiac lesion was confirmed by operative data in twelve of the pairs of siblings and by electrocardiogram, roentgenogram, and clinical manifestations in the remaining pair. Positive additional incidence of congenital heart disease in the family was reported, in all but one case, only if autopsy or operative data proved the diagnosis. The only other case in which an additional member of the family was listed as having congenital heart disease was reported on the basis of undisputable clinical evidence following the progress of the child up to death as a result of his heart condition. Suspected additional family incidence was reported on the basis of clinical findings only where the diagnosis was not proved. Negative reports were declared if the families, when questioned, were not aware of other relatives with congenital heart problems. I t is realized that this does not exclude the possibility of additional congenital heart defects existing in these families. RESULTS
Eesults of each section of the study are tabulated in the following tables. 1. Nature and Similiarity of Lesions in Siblings With Congenital Heart Disease. In 9 of the 13 families reported, the lesions of related afflicted siblings were identical, and, in 4 pairs of siblings, the lesions were similar. Nine of the sib* Gratitude is expressed to Drs. H. H. Hecht, L. B. Viko, JD Mortensen, R, J. Beveridge, L. G. Veasy, H. R. Warner, and A. F. Toronto for their cooperation in this study,
CHBISTENSEN AND NELSON
594
J. Thoracic and Cardiovas. Surg.
FAMILY A
o-
o
•n
o-
2
-D 4
0
3 other
3
normal children 1, Atrial septal defect with valvular pulmonary stenosis (operative findings). 2, Atrial septal defect with valvular pulmonary stenosis (operative findings). 3, Atrial septal defect with valvular pulmonary stenosis (clinical work-up including chest roentgenogram and electrocardiogram). No catheterization studies. b, Ventricular septal defect (operative findings).
FAMILY
B 6 others with no known defect
-•
□-
l
1
3 other normal 4 children 1, Ventricular septal defect (based on clinical data). No catheterization studies at present. 2, Ventricular septal defect (based on autopsy report). 3t Incomplete endocardial cushion defect (clinical data only). !f, Incomplete endocardial cushion defect (clinical data only).
u
FAMILY C
o
I
•
1□
1
i
n
n
o
1 o
1
1
o 1 o
i
1
•
n
1
1
•
2
O
1 o
1 c
o
3 1, Incomplete endocardial cushion defect (operative findings). 2, Incomplete endocardial cushion defect (operative findings). S, Ventricular septal defect (operative findings).
ling pairs were of the same sex while 3 were of opposite sex. The sex relationship of the remaining family in which all the siblings were afflicted is diagrammed under Family E. One pair of the afflicted siblings with identical lesions were twins, and, in another family, one of the afflicted siblings had a monozygous twin with a normal heart. 2. Incidence of Congenital Heart Disease in Additional Members of Families. Table I I demonstrates the results with respect to the possible incidence of congenital heart disease in additional members of families of the afflicted siblings.
Vol. 45. No. 5 May, 1963
CONGENITAL H E A R T D I S E A S E I N SIBLINGS
FAMILY D
□
•
1
595
O
•
■
□
1 2 3 /, Tetralogy of Fallot (operative findings). 2, Tetralogy of Fallot (operative findings). S, Exact nature of lesion undetermined. Patient died at age 1 of cyanotic heart disease (no autopsy). FAMILY E
. . . i
/, 2, 8, 4, 5,
2 3 4 Patent ductus arteriosus (operative findings). Aortic atresia (autopsy d a t a ) . Atrial septal defect, dextrocardia, patent ductus? (catheterization data). Patent ductus arteriosus (operative findings). Patent ductus arteriosus (clinical findings).
TABLE I I .
ADDITIONAL F A M I L Y INCIDENCE OF CONGENITAL
HEART DISEASE
ADDITIONAL FAMILY HISTORY LESION OF SIBLINGS
|
POSITIVE
Atrial septal defect
(4)
1*
Ventricular septal defect
SUSPECTED
|
NEGATIVE
1
2
(2)
0
1
1
Valvular pulmonary stenosis
(1)
0
0
1
Incomplete endocardial cushion defect (ostium primum with cleft mitral leaflet)
(2)
2tt
0
0
0
1
0 0
1 0
2
6
Tetralogy of Fallot
(2)
1§
Semilunar valve stenosis (one aortic, one pulmonary) Patent ductus arteriosus
(1) (1)
0
Totals •See diagram tSee diagram JSee diagram §See diagram || See diagram
111
■
5 of of of of of
Family Family Family Family Family
B. A. C. C. B.
3. Family Histories of 100 Unselected (Non-cardiac) Hospital Admissions. Results of the family histories of the 100 hospitalized persons used as a control are reported in Table I I I . TABLE
III
LESION
POSITIVE
SUSPECTED
NEGATIVE
Any congenital cardiac lesion
4
3
93
C H E I S T E N S E N AND N E L S O N
596
J. Thoracic and Cardiovas. Surg.
Fig. 1.—Usual placement of axial triradius. Pig-. 2.-—Distal placement of axial triradius characteristic of patients with congenital heart disease.
In 4 per cent of the 100 families interviewed there was an awareness of congenital heart disease. This compares with 38 per cent of the 13 sibling families in which congenital heart disease was confirmed. 4. Dermatoglyphic Studies Of 15 patients with congenital heart disease available for study, 11 have dermatoglyphic stigmata (73 per cent). Of 25 without heart disease, 6 have these stigmata (24 per cent). The standard error of the difference is 15 per cent, whereas the actual difference is nearly 50 per cent. These results are similar to those reported by Hale.* 15 The dermatoglyphic stigmata associated with congenital heart disease were not found in nonafflieted members of these families with any greater frequency than in the general population. DISCUSSION
There have been many isolated reports of siblings with similar congenital heart disease. McKeown,16 in reporting a group of 5 afflicted siblings, noted that 3 of the 5 sibling pairs had identical lesions. In analyzing the data of Chelius who reported 19 cases of congenital heart disease with a family incidence, it is apparent that 4 of the 10 cases occurring in these siblings had identical lesions.17 Considering the possibility of hereditary factors, Nadas has reported that, from a series of 2,500 patients with congenital heart disease, 15 families each had two siblings with a congenital heart lesion. He further ob*Gratitude is expressed to Dr. Alfred K. Hale of New Orleans for reviewing the palmar dermatoglyphics collected from these families.
y,0'- 4 ?AM°-
5
CONGENITAL HEART D I S E A S E I N SIBLINGS
5Q7
served that the same lesions were likely to be repeated in siblings of the same sex.18 In comparison, the study reported herewith includes 13 sibling pairs, 9 of which had identical lesions. Lesions were reported as similar, rather than identical, if one of the siblings had associated cardiac pathologic conditions not found in the other sibling. For example, if one sibling had an atrial septal defect and the other had atrial septal defect with an additional associated ventricular septal defect, the lesion was reported as similar, but not identical. One problem encountered in this study was that of detecting additional congenital heart malformations in the sibling families. It was the awareness of an additional family incidence rather than an actual additional family incidence that has been measured. Kauch, in a study of 85,389 school children (ages 5-19) to determine frequency of cardiac problems, reported that 24 per cent of the children discovered with congenital heart disease were totally unaware of the existence of these lesions previous to the examination. 19 Therefore, results from the methods we have used will not be as high as the true incidence of congenital heart disease. An attempt at arriving at a frame of reference was made by doing a control study of 100 families using the same technique and criterion as was used for the sibling families. The existence of one pair of identical twins, one with a congenital heart condition and the other with a normal heart, coincides with other such reports.11"14 This would suggest that etiology of congenital heart disease is not, therefore, a simple genetic factor. However, the frequency with which identical and similar lesions were found in families would indicate that familial factors may play a role. SUMMARY
Thirteen pairs of siblings with congenital heart disease have been studied. In 9 of these sibling pairs, the cardiac lesion was identical, and, in 4 of the pairs, the lesion of the related siblings was similar. Additional family incidence of congenital heart disease was confirmed in 5 of these 13 families. Associated dermatoglyphic stigmata were present in 73 per cent of patients with congenital heart disease compared to 24 per cent of their nonafflicted relatives. I t is concluded that familial factors may be related to the etiology of congenital heart disease. REFERENCES 1. Eichards, M. R., Merritt, K. K., Samuels, M. H., and Langman, A. G.: Congenital Malformations of the Cardiovascular System in a Series of 6,053 Infants, Pediatrics 16: 12, 1955. 2. Adams, F . H . : Congenital Heart Disease: Comments Regarding Incidence and Natural History, California Med. 90: 213, 1959. 3. Dogramaci, I., and Green, H . : Factors in the Etiology of Congenital Heart Anomalies, J . Pediat. 30: 295, 1947. 4. Miller, H. D.: Relation of Maternal Infection to Congenital Malformations of Heart, Mod. Concepts Cardiovas. Dis. 17: 27, 1948. 5. Carleton, R. A., Abelman, W. H., and Hancock, E. W.: Familial Occurrence of Congenital Heart Disease, New England J . Med. 259: 1237, 1958. 6. Annotations: Hereditary and Congenital Heart Disease, Brit. M. J . 1: 704, 1959. 7. Berg, J . M., Crome, L., and France, N . E . : Congenital Cardiac Malformations in Mongolism, Brit. H e a r t J . 22: 331, 1960.
598
C H E I S T E N S E N AND NELSON
J. Thoracic and
Cardiovas. Surg.
8. Campbell, M.: The Genetics of Congenital Heart Disease and Situs Inversus in Siblings, Brit. Heart J . 2 1 : 65, 1959. 9. McKusick, V. A.: The Cardiovascular Aspect of Marfan's Syndrome, Circulation 11: 321, 1955. 10. Freeman, J. T.: Ehlers-Danlos Syndrome, A. M. A. Am. J . Dis. Child. 79: 1049, 1950. 11. Benesova, P . , and Sikl, H . : A Rare Concordant Malformation in Monochoriate Twins, J . Path. & Bact. 67: 367, 1954. 12. Eoss, L. J . : Congenital Cardiovascular Anomalies in Twins, Circulation 20: 327, 1959. 13. Paes, O. de O.: Congenital Cyanotic Heart Disease in One of Monozygotic Twins, Am. Heart J . 52: 929, 1956. 14. Uchida, I . A., and Eowe, E. D . : Discordant Heart Anomalies in Twins, Am. J. Human Genet. 9: 122, 1957. 15. Hale, A. E., Phillips, J . H., and Burch, G. E . : Features of Palmar Dermatoglyphies in Congenital Heart Disease, J . A. M. A. 176: 41, 1961. 16. McKeown, T.: Familial Incidence of Congenital Malformation of Heart, Brit. Heart J . 15: 273, 1953. 17. Chelius, C. J., Eowe, G. G., and Crumpton, C. W.: Familial Aspects of Congenital Heart Disease, Am. J . Cardiol. 9: 508, 1962. 18. Nadas, A. S.: Pediatric Cardiology, Philadelphia, 1957, W. B. Saunders Company, p. 268. 19. Eauch, L. W.: The Incidence of Organic Heart Disease in Children, Am. Heart J. 18: 705, 1939.