International
239
Journal of Cardiology, 29 (1990) 239-240
Elsevier CARD10 11541
Brief Reports
Familial aggregation of defects of the left-sided structures of the heart Samuel Menahem Department
of Paediatrics and Cardiology. Monash Medical Centre, Melbourne,
Australia
(Received and accepted 3 April 1990)
A family is described where a mother and her three children had left heart defects. Three members of a second family were also noted to have such defects. This experience adds support to the hypothesis that in some families, such defects may have an incidence of recurrence higher than the 3% predicted by a multifactorial model. Key words:
Left heart defects;
Family;
Inheritance
Introduction Brenner et al. [l] have reported an increased incidence approaching 13%, for malformations of the chambers of the left heart in relatives of infants born with a hypoplastic left heart syndrome. Others [2,3] have suggested an incidence of congenital heart disease, usually of a similar type, of the order of 12-26% in infants born to a parent with aortic stenosis. Still others have suggested that defects of the left ventricular outflow tract may be developmentally related [4]. A family is described where the mother and all three of her infants had left heart defects, the second dying, from a hypoplastic left heart. Three members of an extended family had aortic valvar stenosis. Case Report: family 1 Baby T, the first infant born to unrelated parents, was found to have moderately severe aortic valvar stenosis confirmed by echocardiography. An open valvotomy of a thickened aortic valve with two leaflets was performed at the age of 17 months. He remains well three years later but requires treatment for asthma.
Correspondence to: Prof. S. Menahem, Dept. of Paediatrics. Monash University, Locked Bag 29, Clayton, Victoria 3168, Australia.
0167-5273/90/$03.50
a 1990 Elsevier Science
Publishers
Baby J, born 18 months later was stated to have a normal fetal echocardiogram at 18 weeks and again at 22 weeks. After an uneventful delivery at term, the infant was noted to feed poorly and developed increasing tachypnoea. On examination, he was in severe heart failure with a poor output. Echocardiography revealed a hypoplastic left ventricle with a small cavity and a very thickened free wall. There was minimal forward flow through a critically stenosed aortic valve with two leaflets into a hypoplastic ascending aorta. There was preductal coarctation and a patent arterial duct of moderate size. The right ventricle was dilated with mild tricuspid incompetence. Despite intensive treatment, ventilation, prostaglandin and inotrope infusions, the infant remained acidotic and died the next day. Baby N, born 17 months later, also had a normal fetal echocardiogram performed at 18, 22 and 32 weeks. When seen at 24 hours, she was noted to have a soft basal systolic murmur and she gradually lost her femoral pulses over the next 24 hours. Echocardiography revealed a slightly thickened, aortic valve with two leaflets, across which there was a minimal gradient. The aortic isthmus tapered down to about 2 mm at the junction with a patent duct of moderate size, the duct then supplying the descending aorta. The coarctation was corrected by a left subclavian aortoplasty and she has done well since. It was then decided to examine the mother, who was unaware of any cardiac abnormality. She was noted to
B.V. (Biomedical
Division)
240
have signs suggestive of trivial aortic valvar stenosis with an ejection click at the left sternal edge and a soft basal systolic murmur. A cross-sectional echocardiogram was normal. Clinical findings in the husband were normal. Case Report: family 2 Baby H was noted to have a murmur on the third day of life consistent with moderately severe aortic valvar stenosis confirmed by cross-secional echocardiography. He was subjected to an open valvotomy and progressed well since. His paternal uncle had an open aortic valvotomy as a young adult while the paternal grandfather had been described as having aortic valvar stenosis. Both the parents had normal cardiac findings. Discussion Three affected children of a mother with trivial aortic valvar stenosis, all with lesions of the left-sided cardiac structures, would suggest that, in this family at least, the defects were under the control of a major gene (or genes) with variable expression. Under this hypothesis, the families in which the gene(s) was segregating would have high proportions (up to 50% in a single gene dominance) of individuals with the “affected” genotype [l]. Expression of the genotype would then depend on additional genetic or environmental modifiers, which might also explain the findings in the second family. Despite careful evaluation of the echocardiogram of baby J by a very experienced obstetrician/echocardiographer, it was thought to be normal even when repeated three weeks later. Unfortunately, a further study in the thud trimester was not performed, as has been suggested by Allan et al. [5], as there appears to be some evidence that a hypoplastic left ventricle may develop if there is little forward flow through the ventricle, for example, the diminished flow being the consequence of a critically stenosed aortic valve [5]. The difficulties in the diagnosis of aortic coarctation by fetal echocardiog-
raphy are also well documented. The indirect signs of a somewhat dilated right ventricle as compared to a slightly smaller left ventricle may be overlooked, while the aortic isthmus tends to be a narrowest part of the aorta in fetal life [5]. Families with defects of the left-sided structures of the heart require careful counselling, as there appears to be a high incidence of subsequently affected pregnancies, especially if either parent (but particularly the mother) have a similar abnormality. Subsequent pregnancies require careful monitoring by fetal echocardiography, which should be repeated into the thud trimester to exclude the possible underdevelopment of a left ventricle subsequent to diminished forward flow. The prenatal diagnosis of a hypoplastic heart syndrome, or critical aortic valvar stenosis, may allow appropria!e planning of the delivery and neonatal intensive care if a surgical option should be considered. Acknowledgement Dr. John Rogers kindly reviewed
the manuscript.
References Brenner JI, Burgka, Schneider DS, Clark EB, Boughman JA. Cardiac malformation in relatives of infants with hypoplastic left heart syndrome. Am J Dis Child 1989;143:1492-1494. Whittemore R, Hohbins JC, Engle MA. Pregnancy and its outcome in women with and without surgical treatment of congenital heart disease. Am J Cardiol 1982;50:641-650. Rose V, Gold RJM, Lindsay G, Allen M. A possible increase in the incidence of congenital heart defects among the offspring of affected parents. J Am Coil Cardiol 1986:6:376-382. Allan LD, Crawford DC, Chita SK, Anderson RH, Tynan MJ. Familial recurrence of congenital heart disease in a prospective series of mothers referred for fetal echocardiography. Am J Cardiol 1986;58:334-337. Allan LD, Chita SK, Anderson RH, Fagg N, Crawford DC, Tynan MJ. Coarctation of the aorta in prenatal life: an echocardiographic, anatomical and functional study. Br Heart J 1988;59:356-360.
239
Journal of Cardiology, 29 (1990) 239-240
Elsevier CARD10 11541
Brief Reports
Familial aggregation of defects of the left-sided structures of the heart Samuel Menahem Department
of Paediatrics and Cardiology. Monash Medical Centre, Melbourne,
Australia
(Received and accepted 3 April 1990)
A family is described where a mother and her three children had left heart defects. Three members of a second family were also noted to have such defects. This experience adds support to the hypothesis that in some families, such defects may have an incidence of recurrence higher than the 3% predicted by a multifactorial model. Key words:
Left heart defects;
Family;
Inheritance
Introduction Brenner et al. [l] have reported an increased incidence approaching 13%, for malformations of the chambers of the left heart in relatives of infants born with a hypoplastic left heart syndrome. Others [2,3] have suggested an incidence of congenital heart disease, usually of a similar type, of the order of 12-26% in infants born to a parent with aortic stenosis. Still others have suggested that defects of the left ventricular outflow tract may be developmentally related [4]. A family is described where the mother and all three of her infants had left heart defects, the second dying, from a hypoplastic left heart. Three members of an extended family had aortic valvar stenosis. Case Report: family 1 Baby T, the first infant born to unrelated parents, was found to have moderately severe aortic valvar stenosis confirmed by echocardiography. An open valvotomy of a thickened aortic valve with two leaflets was performed at the age of 17 months. He remains well three years later but requires treatment for asthma.
Correspondence to: Prof. S. Menahem, Dept. of Paediatrics. Monash University, Locked Bag 29, Clayton, Victoria 3168, Australia.
0167-5273/90/$03.50
a 1990 Elsevier Science
Publishers
Baby J, born 18 months later was stated to have a normal fetal echocardiogram at 18 weeks and again at 22 weeks. After an uneventful delivery at term, the infant was noted to feed poorly and developed increasing tachypnoea. On examination, he was in severe heart failure with a poor output. Echocardiography revealed a hypoplastic left ventricle with a small cavity and a very thickened free wall. There was minimal forward flow through a critically stenosed aortic valve with two leaflets into a hypoplastic ascending aorta. There was preductal coarctation and a patent arterial duct of moderate size. The right ventricle was dilated with mild tricuspid incompetence. Despite intensive treatment, ventilation, prostaglandin and inotrope infusions, the infant remained acidotic and died the next day. Baby N, born 17 months later, also had a normal fetal echocardiogram performed at 18, 22 and 32 weeks. When seen at 24 hours, she was noted to have a soft basal systolic murmur and she gradually lost her femoral pulses over the next 24 hours. Echocardiography revealed a slightly thickened, aortic valve with two leaflets, across which there was a minimal gradient. The aortic isthmus tapered down to about 2 mm at the junction with a patent duct of moderate size, the duct then supplying the descending aorta. The coarctation was corrected by a left subclavian aortoplasty and she has done well since. It was then decided to examine the mother, who was unaware of any cardiac abnormality. She was noted to
B.V. (Biomedical
Division)
240
have signs suggestive of trivial aortic valvar stenosis with an ejection click at the left sternal edge and a soft basal systolic murmur. A cross-sectional echocardiogram was normal. Clinical findings in the husband were normal. Case Report: family 2 Baby H was noted to have a murmur on the third day of life consistent with moderately severe aortic valvar stenosis confirmed by cross-secional echocardiography. He was subjected to an open valvotomy and progressed well since. His paternal uncle had an open aortic valvotomy as a young adult while the paternal grandfather had been described as having aortic valvar stenosis. Both the parents had normal cardiac findings. Discussion Three affected children of a mother with trivial aortic valvar stenosis, all with lesions of the left-sided cardiac structures, would suggest that, in this family at least, the defects were under the control of a major gene (or genes) with variable expression. Under this hypothesis, the families in which the gene(s) was segregating would have high proportions (up to 50% in a single gene dominance) of individuals with the “affected” genotype [l]. Expression of the genotype would then depend on additional genetic or environmental modifiers, which might also explain the findings in the second family. Despite careful evaluation of the echocardiogram of baby J by a very experienced obstetrician/echocardiographer, it was thought to be normal even when repeated three weeks later. Unfortunately, a further study in the thud trimester was not performed, as has been suggested by Allan et al. [5], as there appears to be some evidence that a hypoplastic left ventricle may develop if there is little forward flow through the ventricle, for example, the diminished flow being the consequence of a critically stenosed aortic valve [5]. The difficulties in the diagnosis of aortic coarctation by fetal echocardiog-
raphy are also well documented. The indirect signs of a somewhat dilated right ventricle as compared to a slightly smaller left ventricle may be overlooked, while the aortic isthmus tends to be a narrowest part of the aorta in fetal life [5]. Families with defects of the left-sided structures of the heart require careful counselling, as there appears to be a high incidence of subsequently affected pregnancies, especially if either parent (but particularly the mother) have a similar abnormality. Subsequent pregnancies require careful monitoring by fetal echocardiography, which should be repeated into the thud trimester to exclude the possible underdevelopment of a left ventricle subsequent to diminished forward flow. The prenatal diagnosis of a hypoplastic heart syndrome, or critical aortic valvar stenosis, may allow appropria!e planning of the delivery and neonatal intensive care if a surgical option should be considered. Acknowledgement Dr. John Rogers kindly reviewed
the manuscript.
References Brenner JI, Burgka, Schneider DS, Clark EB, Boughman JA. Cardiac malformation in relatives of infants with hypoplastic left heart syndrome. Am J Dis Child 1989;143:1492-1494. Whittemore R, Hohbins JC, Engle MA. Pregnancy and its outcome in women with and without surgical treatment of congenital heart disease. Am J Cardiol 1982;50:641-650. Rose V, Gold RJM, Lindsay G, Allen M. A possible increase in the incidence of congenital heart defects among the offspring of affected parents. J Am Coil Cardiol 1986:6:376-382. Allan LD, Crawford DC, Chita SK, Anderson RH, Tynan MJ. Familial recurrence of congenital heart disease in a prospective series of mothers referred for fetal echocardiography. Am J Cardiol 1986;58:334-337. Allan LD, Chita SK, Anderson RH, Fagg N, Crawford DC, Tynan MJ. Coarctation of the aorta in prenatal life: an echocardiographic, anatomical and functional study. Br Heart J 1988;59:356-360.
