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Supravalvular Aortic Stenosis
Supravalvular Aortic Stenosis * Report of a Family with Peculiar Somatic Features and Normal Intelligence Andrew 1. Lewis, M.D.; Patrick A. Ongley, M.B., Ch.B., F.C.C.P.; Owings W. Kincaid, M.D.; and Donald G. Ritter, M.D., F.C.C.P.
Supravalvular aortic stenosis bas been recognized as a distinct uoufamillal syudrome associated with peculiar facies and mental retardation (SVAS syudrome). It has also been described as a sporadic or famnia! lesion associated with normal somatic features and normal intelligence. COnical and experimental data have impUcated infantile hypercalcemia in the etiology of the SVAS syudrome. It had been suggested previously that the separation of SVAS into three distinct clinical forms was not absolute. The present report is concemed with a family in which five of nine sibUngs were found to have SVAS associated with somatic features typical of the SVAS syudrome but with normal intelligence. Chromosome studies were negative.
heart murmur had been noted at birth but subsequent growth, development, and exercise tolerance were normal. Her appearance at age seven years is shown in Figure 2. On physical examination she had a high forehead, epicanthic folds, and mild prognathism but no distinctiv(' dental abnormalities. The blood pressure was 114 mm Hg systolic and 70 diastolic in the right arm and 100/80 in the left arm. A systolic thrill was palpable over the carotid arteries but the precordium was quiet. A normal first heart sound was followed by an ejection sound and a grade 3/6 ejection murmur which was maxintal along the upper right sternal border and radiated into the carotids and along the left sternal border to the apex. The second sound was normally split. Routine studies of blood and urine gave normal results. The electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 60 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed a heart of normal size (cardiothoracic ratio, 0.38). The aortic arch
It has been recognized that supravalvular aortic stenosis (SVAS) may occur sporadically as a distinct syndrome associated with peculiar facies and mental retardation (SVAS syndrome).1 The lesion may also be associated with normal facies and intelligence, occurring in either a familial or a sporadic form. However, it has been pointed out by others that this distinction may not be absolute. 2 . 5 We have recently had the opportunity to study a family in which five of nine siblings were found to have SVAS associated with normal intelligence and peculiar somatic features, similar to those described by Williams and associates 1 and others. 6 ' s These five children were studied in detail and form the basis of the present report. None of the four other siblings was examined. One was known to have a heart murmur but was said to have normal facial features, two were professional pilots who had no known heart murmur, and one had died of pneumonia in infancy. A group photograph of the five children at the time of the present report is shown in Figure 1. REPoRT OF
CASES
CASE 1 The oldest of the five children examined was a 15-yearold girl; she was the product of a normal pregnancy. A 1. Children at time of present report. Front row, left to right: case 1, case 2; back row, left to right: case 3, case 4, case 5.
FiCURE
-Mayo Clinic and Mayo Foundation: Section of Medicine (Dr. Lewis). of Pediatrics (Drs. Ongley and Ritter), and of Roentgenology (Dr. Kincaid).
372
373
SUPRAVALVULAR AORTIC STENOSIS CAsE 2
FIGURE 2 (case 1). Appearance at age seven years. was on the left and was not prominent. The puhnonary vasculature was normal. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 106, verbal IQ of 113, and performance IQ of 97. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 3. Operation was not recommended.
The next oldest sister, a 14-year-old girl, was the product of a normal pregnancy and had been noted to have a heart murmur at birth. Her growth. development, and exercise tolerance were normal. Her appearance at about eight years of age is shown in Figure 4. On physical examination she had a broad forehead with full cheeks, prominence of the upper lip, and loss of the nasolabial folds. The medial lower incisors were hypoplastic. The blood pressure was 130/50 in the right arm and nO/64 in the left arm. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating into the neck and along the left sternal border. The second heart sound was normally split. Results of routine blood and urine tests were unremarkable. The electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 75 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed the heart to be of normal size (cardiothoracic ratio, 0.38). The aortic arch was on the left and was not prominent. The pulmonary vasculature was normal. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 105, verbal IQ of 100, and performance IQ of no. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 5. Operation was not recommended. CASE 3
The boy, 13 years old, was the product of a normal pregnancy but premature birth (birth weight, 3% lb). A heart murmur had been noted at birth. Subsequent growth, development, and exercise tolerance were normal. His appearance at age five years is shown in Figure 6.
FIGURE 3 (case 1). Angiocardiogram after injection of contrast medium into left ventricle. Left, Anteroposterior view. Right, Lateral view.
DIS. CHEST, VOL. 55, NO.5, MAY 1969
LEWIS ET AL
374 Table I-Cardiac CatheteriZtJtion Datae Pressures (nun Hg) Case
RV
MPA
1
27 0008 28 4to6
26
2 3
4
5
26 0007 68 4to 12
31 2007
Distal PA
Cardiac Aorta immedi- Distal ately Above Ascending Index Valve Aorta (L/min/m2 ) LV
Wedge 12
"8
150 1 to 14 128 3to 13
6"
28
16
S
S-
12
24
9
65
15
RPA34
TI
LPA26
S
14
5
10
26
15
8"
TO
=
=
150
78
118 73
4.6
122
67 117
104
5.7
110
5.1
114 1 t08 189 2009
64
64
55
55
115 2to 10
68
188
4.8
102
Comment Gradient in proximal ascending aorta, 32 mm Hg Max. gradient across aortic valve area, 6 nun Hg; no detectable gradient in ascending aorta Gradient in proximal ascending aorta, 13 mm Hg Gradient in proximal ascending aorta,
78 6.6
Hg· RBA, 135. LBA 104 mm, 65' '65
Gradient across aortic valve area, 13 mm Hgt
=
°Abbreviations: RV right ventricle; LV left ventricle; MPA = main pulmonary artery; PA = pulmonary artery; RBA right brachial artery; LBA = left brachial artery. fWith double-lumen catheter there was 20-mm Hg gradient across LV outflow tract. Possibility of artifact could not be excluded. Normal postextrasystolic beat potentiation was present. raphy are shown in Tables 1 and 2 and Figure 7. Operation was not recommended.
On physical examination his forehead was broad and his cheeks were full. His upper lip was prominent and there was loss of the nasolabial folds. The upper lateral incisors were small. The blood pressure was 100/70 in both anns. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating into the neck and along the left sternal border. The second heart sound was normally split. Routine blood and urine tests gave normal results. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 30 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed normal heart size (cardiothoracic ratio, 0.40) with a left aortic arch and normal pulmonary vessels. The aorta was not prominent. Psychologic testing ~echsler Intelligence Scale for Children) revealed a full-scale IQ of 102, verbal IQ of 104, and perfonnance IQ of 104. The results of cardiac catheterization and angiocardiog-
4 The ll-year-old girl also was the product of a normal pregnancy. A heart murmur had been noted at birth. Subsequent growth, development, and exercise tolerance were normal. Her appearance at age six years is shown in Figure 8. On physical examination she had a broad forehead, full cheeks, and loss of the nasolabial folds. The upper lateral incisors were small. The blood pressure was 110/70 in the right arm and 105/70 in the left arm. A systolic thrill was palpable over the carotid arteries, along the upper right sternal border, and along the left sternal border. A normal first heart sound was followed by a grade 4/6 ejection murmur maximal along the upper right sternal border and radiating into the neck vessels, along the left sternal border, and into the posterior part of the thorax. The second heart sound was normally split. CASE
Table 2-Angiocardiographic DattJ e
SVAS
Sinuses of Valsalva
Ascending Aorta Distal to SVAS
Coronary Arteries
Pulmonary Arteries
Case
Type
1
Localized
Mild
Nonna!
Normal
Normal
Nonnal
2 3
Localized Localized
Mild Mild
Normal Normal
Normal Normal
4
Localized
Marked
Normal
5
Localized
Mild
Normal
Normal LCA ostium at or immediatelyadjacent to area of SVAS Moderate dilatation, RCA; mild dilatation, proximal LeA LeA. ostium at or immediately adjacent to area of SVAS
Normal Mild stenosis, RUL branch of RPA Multifle bilateral perip eraI pulmonary artery stenoses Normal
Severity
=
=
Hypoplastic for 1.5 em distal to area of SVAS Normal
Other Mild LVH and LAE Moderate LVH Marked LVH; moderate RVH
=
°Abbreviations: SVAS supravalvular aortic stenosis; LVH left ventricular hypertrophy; RVH right ventricular hypertrophy; LAE = left atrial enlargement; LeA left coronary artery; RCA right coronary artery; RUL = right upper lobe; RPA right pulmonary artery.
=
=
=
DIS. CHEST, VOL. 55, NO.5, MAY 1969
375
SUPRAVALVULAR AORTIC STENOSIS
FiGURE 6 (case 3). Appearance at age five years. FIGURE
4 (case 2). Appearance at about age eight years.
Results of routine studies of blood and urine were normal. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 70 degrees in the frontal plane and normal voltages. The thoracic roentgenogram showed a normal heart size (cardiothoracic ratio, 0.45). The aorta was not prominent and the arch was on the left. The
FIGURE
pulmonary vessels were normal. There appeared to be mild left atrial enlargement. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 107, verbal IQ of 111, and performance IQ of 100. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 9. The supravalvular aortic stenosis was corrected surgically.
5 (case 2). Angiocardiogram after injection of contrast medium into left ventricle.
Left, Anteroposterior view. Right, Lateral view. DIS. CHEST, VOL. 55, NO.5, MAY 1969
LEWIS ET AL
376
FIGURE 7 (case 3). Angiocardiogram after injection of contrast medium into left ventricle.
Left, Anteroposterior view. Right, Lateral view.
(Operation by Dr. D. C. McGoon, Section of Surgery, Mayo Clinic.) At the time of operation but prior to the repair, the pressure in the left ventricle was 180/10 and the pressure in the ascending aorta above the area of stenosis was 115/60. The repair consisted of excision of a portion of the thickened intimal ridge and enlargement of the aortic root with a pericardial patch, as previously described.• After the repair, the left ventricular systolic pressure was 110 to 95 mm Hg and the aortic pressure was 110 mm Hg. No attempt was made to repair the peripheral pulmonary artery stenoses. The postoperative course was uneventful.
CASES The youngest child, a nine-year-old girl, was the product of a normal pregnancy. A heart murmur had been noted at birth, but subsequent growth, development, and exercise tolerance were normal. Her appearance at age five years is shown in Figure 10. On physical examination she had a broad forehead, full cheeks, fullness of the upper lip, and loss of the nasolabial folds. Her chin was pointed but her dental structure was normal. The blood pressure was 96/74 in the left arm. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by an ejection sound and a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating to the neck and along the left sternal border to the apex. The second heart sound was normally split. Routine blood and urine tests gave normal results. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 70 degrees in the frontal plane and normal voltages. The thoracic roentgenogram showed a normal heart size (cardiothoracic ratio, 0.45) with a normal left aortic arch and normal pulmonary vasculature. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 107, verbal IQ of 104, and performance IQ of 108. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 11. Operation was not recommended. SPECIAL STUDIES
FIGURE 8 (case 4). Appearance at age six years.
Chromosomal analysis demonstrated a normal number of autosomal and sex chromosomes in each case. In four of the cases (1, 2, 3, and 5) one pair DIS. CHEST, VOL. 55, NO.5, MAY 1969
377
SUPRAVALVULAR AORTIC STENOSIS
FIGURE 9 (case 4). Angiocardiogram after injection of contrast medium into left venbicle. Left, Anteroposterior view. Right, Lateral view.
of chromosomes of the G group appeared larger than average, but this was of doubtful significance. Results of chromosomal analysis on both parents were normal. DISCUSSION
Williams and co-workersl were the first to describe the association of SVAS, mental deficiency, and peculiar facies. Beuren and co-workers7 noted that multiple peripheral pulmonary artery stenoses may be present with other features of the syndrome; they also noted the occurrence of mandibular hypoplasia and occasional dental abnormalities.
FIGURE
10 (case 5). Appearance at age five years.
DIS. CHEST, VOL. 55, NO.5, MAY 1969
The association with multiple peripheral pulmonary artery stenoses has been confirmed by a number of authors. 8-11 This lesion has also been found in the sporadic11-l3 and familial 11 forms of SVAS. Black and Bonham Carter6 noted the facial similarity hetween patients with infantile hypercalcemia and those with SVAS syndrome. Garcia and associates14 documented the coexistence of infantile hypercalcemia and the SVAS syndrome. The studies by Friedman and Roberts l ll,l6 have added experimental support to this relationship. It has been tempting to conclude that the syndrome described by Williams and others is indeed a distinct entity causally related to infantile hypercalcemia. Recent reports have tended to confuse this association. Page and associates8 reported on the occurrence of SVAS in identical twins with the characteristic facies and mental retardation. Rastelli and co-workers· mentioned the occurrence of SVAS in a patient with the characteristic facies but with normal intelligence. Antia and associates' have further pointed out the lack of distinction between the familial and sporadic forms and the SVAS syndrome. Five of their patients had normal facial features, mental retardation, and abnormal dental structure; the sibling of one had the characteristic facies and dental abnormality but normal intelligence. The present report is the first to note the familial
LEWIS ET AL
378
FIGURE 11 (case 5). Angiocardiogram after injection of contrast medium into left ventricle. Left, Anteroposterior view. Right, Lateral view.
occurrence of SVAS associated with peculiar somatic features but normal intelligence. All the children showed facial features similar to those previously described. Three of the children had dental abnormalities as described by Beuren and co-workers. 7 Marked SVAS was present in one patient and mild stenosis in the others. In two patients (cases 2 and 5) a gradient was present between the left ventricle and aorta, but a distinct supravalvular gradient was not detected. In all patients, however, angiocardiography demonstrated a distinct area of SVAS and a normal aortic valve. 17 Peripheral pulmonary artery stenosis was noted in two patients. Chromosomal studies have been reported by a number of authors, but no distinctive abnormalities have been noted in any of the forms of SVAS.7.1o. 18·21 Merritt and co-workers9 did describe one patient with the SVAS syndrome and an extra chromosome in the 19-20 group. The relationship of this anomaly to the presence of SVAS was doubtful. No definite chromosome abnormalities were noted in the present cases. REFERENCES
1 WILLIAMS, J. C. P., BARRATr-BoYES, B. G., AND LoWE, J. B.: Supravalvular aortic stenosis, Circulation, 24:
1311,1961.
VOGEL, J. H. K., AND BLOUNT, S. G., JR.: CUnical evaluation in localizing level of obstruction to outflow from left ventricle: Importance of early systolic ejection click, Amer. ]. Cardiol., 15:782, 1965. 3 PAGE, H. L., JR., VOGEL, J. H. K., PRYOR, R, AND BLOUNT, S. G., JR.: Unusual observations in supravalvular aortic stenosis (abstract), Circulation, 32 (Suppl 2): 166,1965. 4 RASTELLI, G. C., MCGOON, D. C., ONGLEY, P. A., MANICIN, H. T., AND Knua.IN, J. W.: Surgical. treatment of supravalvular aortic stenosis: Report of 16 cases and review of literature, J. Thorac. Cardiovasc. Surg., 51:
2
873,1966. 5 ANnA, A. U., WILTSE, H. E., ROWE, R. D., Prrr, E. L., LEVIN, S., OTrEsEN, O. E., AND CooKE, R. E.: Pathogenesis of the supravalvuIar aortic stenosis syndrome,
]. Pediat., 71:431, 1967.
6 BLAClt, J. A., AND BONHAM CARTER, R E.: Association between aortic stenosis and facies of severe infantile hypercalcaemia, Lancet, 2:745, 1963. 7 BEUREN, A. J., SCHULZE, C., EBERLE, P., HARMJANZ, D., AND ApITZ, J.: The syndrome of supravalvular aortic stenosis, peripheral pulmonary stenosis, mental retardation and similar facial appearance, Amer. ]. Cardiol., 13:471, 1964. 8 FRASER, D., KmD, B. S. L., KOOH, S. W., AND PAUNIER, L.: A new look at infantile hypercalcemia, Pediat. Clin. N. Amer., 13:503, 1966. 9 MEIUIITr, A. D., PALMER, C. G., LURIE, P. R, AND PETRY, E. L.: Supravalvular aortic stenosis: Genetic and clinical studies (abstract), ]. Lab. Clin. Med., 62: 995,1963. 10 LOGAN, W. F. W. E., JONES, E. W., WALKER, E.,
DIS. CHEST, VOL. 55, NO.5, MAY 1969
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SUPRAVALVULAR AORTIC STENOSIS
11
12 13
14
15
16
COULSHED, N., AND EpSTEIN, E. J., Familial supravalvular aortic stenosis, Brit. Heart. 1., 27:547, 1965. OTTEsEN, O. E., ANnA, A. U., AND ROWE, R. D.: Peripheral vascular anomalies associated with the supravalvular aortic stenosis syndrome, Radiology, 86:430, 1966. BOURASSA, M. G., AND CAMPEAU, L.: Combined supravalvular aortic and pulmonic stenosis, Circulation, 28: 572,1963. KURLANDER, G. J., PETRY, E. L., TAYBI, H., LURIE, P. R., AND CA~IPBELL, J. A.: Supravalvular aortic stenosis: Roentgen analysis of 27 cases, Amer. I. Roentgen., 98:782, 1966. GARCIA, R. E., FRIEDMAN, W. F., KABACK, M. M., AND ROWE, R. D.: Idiopathic hypercalcemia and supravalvular aortic stenosis, New Eng. 1. Med., 271:117, 1964. FRIEDMAN, W. F., AND ROBERTS, W. C.: Vitamin D and the supravalvular aortic stenosis syndrome: The transplacental effects of vitamin D on the aorta of the rabbit, Circulation, 34:77, 1966. FRIEDMAN, W. F.: Vitamin D as a cause of the supra-
17 18 19 20 21
valvular aortic stenosis syndrome, Amer. Hearl 1., 73: 718,1967. TAKEKAWA, S. D., KINCAID, O. W., TITUS, J. L., AND DUSHANE, J. W.: Congenital aortic stenosis, Amer. ]. Roentgen., 98:800, 1966. EBERLE, P., AND BEUREN, A. J.: Chromosome studies in patients with supravalvular aortic stenosis, Lancet, 2: 438,1963. JOSEPH, M. C., POUNI, P. E., AND GoLD, R. G.: Chromosome studies in patients with supravalvular aortic stenosis (Letter to the editor), Lancet, 2:788, 1963. GROUCHY, J. DE, AND EMERIT, I.: Chromosome studies in patients with supravalvular aortic stenosis (Letter to the editor), Lancet, 2:789, 1963. KAHLER, R. L., BRAUNWALD, E., PLAUTH, W. H., JR., AND MORROW, A. G.: Familial congenital heart disease: Familial occurrence of atrial septal defect with A-V conduction abnormalities; supravalvular aortic and pulmonic stenosis; and ventricular septal defect, Amer. 1. Med., 40:384, 1966.
Reprint requests: Section of Publications, Mayo Clinic, Rochester, Minnesota 55901.
OBSERVAnONS ON CAPILLARY AND VENOUS PULSE The presence of large and rapidly falling pulsations is demonstrated in an exquisite manner in insufficiency of the aortic valves. The manner of the appearance and disappearance of the capillary pulse, is objectively as characteristic a sign of aortic insufficiency as the exquisitely abrupt pulse is to the palpating finger. It is, generally, impossible to say in which finger nail is the phenomenon the most distinct, but it seems to occur
most frequently in the index finger. The white zone is usually found in the third quarter of the nail, measuring from the matrix, and the pulsation is at times more distinct in the lower part, at other times in the upper part. Quincke, H. (1842-1922) in Willius, F. A. and Keys, T. E.: Classics of Cardiology, (Vol. II) Dover Publications, New York, 1941
Postgraduate Course on Intensive Management of Respiratory Diseases Winnipeg, October 16-18, 1969
(See pages 441,442 this issue, for complete program)
DIS. CHEST, VOL. 55, NO.5, MAY 1969
Supravalvular aortic stenosis bas been recognized as a distinct uoufamillal syudrome associated with peculiar facies and mental retardation (SVAS syudrome). It has also been described as a sporadic or famnia! lesion associated with normal somatic features and normal intelligence. COnical and experimental data have impUcated infantile hypercalcemia in the etiology of the SVAS syudrome. It had been suggested previously that the separation of SVAS into three distinct clinical forms was not absolute. The present report is concemed with a family in which five of nine sibUngs were found to have SVAS associated with somatic features typical of the SVAS syudrome but with normal intelligence. Chromosome studies were negative.
heart murmur had been noted at birth but subsequent growth, development, and exercise tolerance were normal. Her appearance at age seven years is shown in Figure 2. On physical examination she had a high forehead, epicanthic folds, and mild prognathism but no distinctiv(' dental abnormalities. The blood pressure was 114 mm Hg systolic and 70 diastolic in the right arm and 100/80 in the left arm. A systolic thrill was palpable over the carotid arteries but the precordium was quiet. A normal first heart sound was followed by an ejection sound and a grade 3/6 ejection murmur which was maxintal along the upper right sternal border and radiated into the carotids and along the left sternal border to the apex. The second sound was normally split. Routine studies of blood and urine gave normal results. The electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 60 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed a heart of normal size (cardiothoracic ratio, 0.38). The aortic arch
It has been recognized that supravalvular aortic stenosis (SVAS) may occur sporadically as a distinct syndrome associated with peculiar facies and mental retardation (SVAS syndrome).1 The lesion may also be associated with normal facies and intelligence, occurring in either a familial or a sporadic form. However, it has been pointed out by others that this distinction may not be absolute. 2 . 5 We have recently had the opportunity to study a family in which five of nine siblings were found to have SVAS associated with normal intelligence and peculiar somatic features, similar to those described by Williams and associates 1 and others. 6 ' s These five children were studied in detail and form the basis of the present report. None of the four other siblings was examined. One was known to have a heart murmur but was said to have normal facial features, two were professional pilots who had no known heart murmur, and one had died of pneumonia in infancy. A group photograph of the five children at the time of the present report is shown in Figure 1. REPoRT OF
CASES
CASE 1 The oldest of the five children examined was a 15-yearold girl; she was the product of a normal pregnancy. A 1. Children at time of present report. Front row, left to right: case 1, case 2; back row, left to right: case 3, case 4, case 5.
FiCURE
-Mayo Clinic and Mayo Foundation: Section of Medicine (Dr. Lewis). of Pediatrics (Drs. Ongley and Ritter), and of Roentgenology (Dr. Kincaid).
372
373
SUPRAVALVULAR AORTIC STENOSIS CAsE 2
FIGURE 2 (case 1). Appearance at age seven years. was on the left and was not prominent. The puhnonary vasculature was normal. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 106, verbal IQ of 113, and performance IQ of 97. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 3. Operation was not recommended.
The next oldest sister, a 14-year-old girl, was the product of a normal pregnancy and had been noted to have a heart murmur at birth. Her growth. development, and exercise tolerance were normal. Her appearance at about eight years of age is shown in Figure 4. On physical examination she had a broad forehead with full cheeks, prominence of the upper lip, and loss of the nasolabial folds. The medial lower incisors were hypoplastic. The blood pressure was 130/50 in the right arm and nO/64 in the left arm. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating into the neck and along the left sternal border. The second heart sound was normally split. Results of routine blood and urine tests were unremarkable. The electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 75 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed the heart to be of normal size (cardiothoracic ratio, 0.38). The aortic arch was on the left and was not prominent. The pulmonary vasculature was normal. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 105, verbal IQ of 100, and performance IQ of no. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 5. Operation was not recommended. CASE 3
The boy, 13 years old, was the product of a normal pregnancy but premature birth (birth weight, 3% lb). A heart murmur had been noted at birth. Subsequent growth, development, and exercise tolerance were normal. His appearance at age five years is shown in Figure 6.
FIGURE 3 (case 1). Angiocardiogram after injection of contrast medium into left ventricle. Left, Anteroposterior view. Right, Lateral view.
DIS. CHEST, VOL. 55, NO.5, MAY 1969
LEWIS ET AL
374 Table I-Cardiac CatheteriZtJtion Datae Pressures (nun Hg) Case
RV
MPA
1
27 0008 28 4to6
26
2 3
4
5
26 0007 68 4to 12
31 2007
Distal PA
Cardiac Aorta immedi- Distal ately Above Ascending Index Valve Aorta (L/min/m2 ) LV
Wedge 12
"8
150 1 to 14 128 3to 13
6"
28
16
S
S-
12
24
9
65
15
RPA34
TI
LPA26
S
14
5
10
26
15
8"
TO
=
=
150
78
118 73
4.6
122
67 117
104
5.7
110
5.1
114 1 t08 189 2009
64
64
55
55
115 2to 10
68
188
4.8
102
Comment Gradient in proximal ascending aorta, 32 mm Hg Max. gradient across aortic valve area, 6 nun Hg; no detectable gradient in ascending aorta Gradient in proximal ascending aorta, 13 mm Hg Gradient in proximal ascending aorta,
78 6.6
Hg· RBA, 135. LBA 104 mm, 65' '65
Gradient across aortic valve area, 13 mm Hgt
=
°Abbreviations: RV right ventricle; LV left ventricle; MPA = main pulmonary artery; PA = pulmonary artery; RBA right brachial artery; LBA = left brachial artery. fWith double-lumen catheter there was 20-mm Hg gradient across LV outflow tract. Possibility of artifact could not be excluded. Normal postextrasystolic beat potentiation was present. raphy are shown in Tables 1 and 2 and Figure 7. Operation was not recommended.
On physical examination his forehead was broad and his cheeks were full. His upper lip was prominent and there was loss of the nasolabial folds. The upper lateral incisors were small. The blood pressure was 100/70 in both anns. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating into the neck and along the left sternal border. The second heart sound was normally split. Routine blood and urine tests gave normal results. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 30 degrees in the frontal plane and normal voltages. A thoracic roentgenogram showed normal heart size (cardiothoracic ratio, 0.40) with a left aortic arch and normal pulmonary vessels. The aorta was not prominent. Psychologic testing ~echsler Intelligence Scale for Children) revealed a full-scale IQ of 102, verbal IQ of 104, and perfonnance IQ of 104. The results of cardiac catheterization and angiocardiog-
4 The ll-year-old girl also was the product of a normal pregnancy. A heart murmur had been noted at birth. Subsequent growth, development, and exercise tolerance were normal. Her appearance at age six years is shown in Figure 8. On physical examination she had a broad forehead, full cheeks, and loss of the nasolabial folds. The upper lateral incisors were small. The blood pressure was 110/70 in the right arm and 105/70 in the left arm. A systolic thrill was palpable over the carotid arteries, along the upper right sternal border, and along the left sternal border. A normal first heart sound was followed by a grade 4/6 ejection murmur maximal along the upper right sternal border and radiating into the neck vessels, along the left sternal border, and into the posterior part of the thorax. The second heart sound was normally split. CASE
Table 2-Angiocardiographic DattJ e
SVAS
Sinuses of Valsalva
Ascending Aorta Distal to SVAS
Coronary Arteries
Pulmonary Arteries
Case
Type
1
Localized
Mild
Nonna!
Normal
Normal
Nonnal
2 3
Localized Localized
Mild Mild
Normal Normal
Normal Normal
4
Localized
Marked
Normal
5
Localized
Mild
Normal
Normal LCA ostium at or immediatelyadjacent to area of SVAS Moderate dilatation, RCA; mild dilatation, proximal LeA LeA. ostium at or immediately adjacent to area of SVAS
Normal Mild stenosis, RUL branch of RPA Multifle bilateral perip eraI pulmonary artery stenoses Normal
Severity
=
=
Hypoplastic for 1.5 em distal to area of SVAS Normal
Other Mild LVH and LAE Moderate LVH Marked LVH; moderate RVH
=
°Abbreviations: SVAS supravalvular aortic stenosis; LVH left ventricular hypertrophy; RVH right ventricular hypertrophy; LAE = left atrial enlargement; LeA left coronary artery; RCA right coronary artery; RUL = right upper lobe; RPA right pulmonary artery.
=
=
=
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FiGURE 6 (case 3). Appearance at age five years. FIGURE
4 (case 2). Appearance at about age eight years.
Results of routine studies of blood and urine were normal. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 70 degrees in the frontal plane and normal voltages. The thoracic roentgenogram showed a normal heart size (cardiothoracic ratio, 0.45). The aorta was not prominent and the arch was on the left. The
FIGURE
pulmonary vessels were normal. There appeared to be mild left atrial enlargement. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 107, verbal IQ of 111, and performance IQ of 100. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 9. The supravalvular aortic stenosis was corrected surgically.
5 (case 2). Angiocardiogram after injection of contrast medium into left ventricle.
Left, Anteroposterior view. Right, Lateral view. DIS. CHEST, VOL. 55, NO.5, MAY 1969
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FIGURE 7 (case 3). Angiocardiogram after injection of contrast medium into left ventricle.
Left, Anteroposterior view. Right, Lateral view.
(Operation by Dr. D. C. McGoon, Section of Surgery, Mayo Clinic.) At the time of operation but prior to the repair, the pressure in the left ventricle was 180/10 and the pressure in the ascending aorta above the area of stenosis was 115/60. The repair consisted of excision of a portion of the thickened intimal ridge and enlargement of the aortic root with a pericardial patch, as previously described.• After the repair, the left ventricular systolic pressure was 110 to 95 mm Hg and the aortic pressure was 110 mm Hg. No attempt was made to repair the peripheral pulmonary artery stenoses. The postoperative course was uneventful.
CASES The youngest child, a nine-year-old girl, was the product of a normal pregnancy. A heart murmur had been noted at birth, but subsequent growth, development, and exercise tolerance were normal. Her appearance at age five years is shown in Figure 10. On physical examination she had a broad forehead, full cheeks, fullness of the upper lip, and loss of the nasolabial folds. Her chin was pointed but her dental structure was normal. The blood pressure was 96/74 in the left arm. A systolic thrill was palpable in the suprasternal notch but the precordium was quiet. A normal first heart sound was followed by an ejection sound and a grade 3/6 ejection murmur maximal along the upper right sternal border and radiating to the neck and along the left sternal border to the apex. The second heart sound was normally split. Routine blood and urine tests gave normal results. An electrocardiogram showed normal sinus rhythm with a mean QRS axis of + 70 degrees in the frontal plane and normal voltages. The thoracic roentgenogram showed a normal heart size (cardiothoracic ratio, 0.45) with a normal left aortic arch and normal pulmonary vasculature. Psychologic testing (Wechsler Intelligence Scale for Children) revealed a full-scale IQ of 107, verbal IQ of 104, and performance IQ of 108. The results of cardiac catheterization and angiocardiography are shown in Tables 1 and 2 and Figure 11. Operation was not recommended. SPECIAL STUDIES
FIGURE 8 (case 4). Appearance at age six years.
Chromosomal analysis demonstrated a normal number of autosomal and sex chromosomes in each case. In four of the cases (1, 2, 3, and 5) one pair DIS. CHEST, VOL. 55, NO.5, MAY 1969
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FIGURE 9 (case 4). Angiocardiogram after injection of contrast medium into left venbicle. Left, Anteroposterior view. Right, Lateral view.
of chromosomes of the G group appeared larger than average, but this was of doubtful significance. Results of chromosomal analysis on both parents were normal. DISCUSSION
Williams and co-workersl were the first to describe the association of SVAS, mental deficiency, and peculiar facies. Beuren and co-workers7 noted that multiple peripheral pulmonary artery stenoses may be present with other features of the syndrome; they also noted the occurrence of mandibular hypoplasia and occasional dental abnormalities.
FIGURE
10 (case 5). Appearance at age five years.
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The association with multiple peripheral pulmonary artery stenoses has been confirmed by a number of authors. 8-11 This lesion has also been found in the sporadic11-l3 and familial 11 forms of SVAS. Black and Bonham Carter6 noted the facial similarity hetween patients with infantile hypercalcemia and those with SVAS syndrome. Garcia and associates14 documented the coexistence of infantile hypercalcemia and the SVAS syndrome. The studies by Friedman and Roberts l ll,l6 have added experimental support to this relationship. It has been tempting to conclude that the syndrome described by Williams and others is indeed a distinct entity causally related to infantile hypercalcemia. Recent reports have tended to confuse this association. Page and associates8 reported on the occurrence of SVAS in identical twins with the characteristic facies and mental retardation. Rastelli and co-workers· mentioned the occurrence of SVAS in a patient with the characteristic facies but with normal intelligence. Antia and associates' have further pointed out the lack of distinction between the familial and sporadic forms and the SVAS syndrome. Five of their patients had normal facial features, mental retardation, and abnormal dental structure; the sibling of one had the characteristic facies and dental abnormality but normal intelligence. The present report is the first to note the familial
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FIGURE 11 (case 5). Angiocardiogram after injection of contrast medium into left ventricle. Left, Anteroposterior view. Right, Lateral view.
occurrence of SVAS associated with peculiar somatic features but normal intelligence. All the children showed facial features similar to those previously described. Three of the children had dental abnormalities as described by Beuren and co-workers. 7 Marked SVAS was present in one patient and mild stenosis in the others. In two patients (cases 2 and 5) a gradient was present between the left ventricle and aorta, but a distinct supravalvular gradient was not detected. In all patients, however, angiocardiography demonstrated a distinct area of SVAS and a normal aortic valve. 17 Peripheral pulmonary artery stenosis was noted in two patients. Chromosomal studies have been reported by a number of authors, but no distinctive abnormalities have been noted in any of the forms of SVAS.7.1o. 18·21 Merritt and co-workers9 did describe one patient with the SVAS syndrome and an extra chromosome in the 19-20 group. The relationship of this anomaly to the presence of SVAS was doubtful. No definite chromosome abnormalities were noted in the present cases. REFERENCES
1 WILLIAMS, J. C. P., BARRATr-BoYES, B. G., AND LoWE, J. B.: Supravalvular aortic stenosis, Circulation, 24:
1311,1961.
VOGEL, J. H. K., AND BLOUNT, S. G., JR.: CUnical evaluation in localizing level of obstruction to outflow from left ventricle: Importance of early systolic ejection click, Amer. ]. Cardiol., 15:782, 1965. 3 PAGE, H. L., JR., VOGEL, J. H. K., PRYOR, R, AND BLOUNT, S. G., JR.: Unusual observations in supravalvular aortic stenosis (abstract), Circulation, 32 (Suppl 2): 166,1965. 4 RASTELLI, G. C., MCGOON, D. C., ONGLEY, P. A., MANICIN, H. T., AND Knua.IN, J. W.: Surgical. treatment of supravalvular aortic stenosis: Report of 16 cases and review of literature, J. Thorac. Cardiovasc. Surg., 51:
2
873,1966. 5 ANnA, A. U., WILTSE, H. E., ROWE, R. D., Prrr, E. L., LEVIN, S., OTrEsEN, O. E., AND CooKE, R. E.: Pathogenesis of the supravalvuIar aortic stenosis syndrome,
]. Pediat., 71:431, 1967.
6 BLAClt, J. A., AND BONHAM CARTER, R E.: Association between aortic stenosis and facies of severe infantile hypercalcaemia, Lancet, 2:745, 1963. 7 BEUREN, A. J., SCHULZE, C., EBERLE, P., HARMJANZ, D., AND ApITZ, J.: The syndrome of supravalvular aortic stenosis, peripheral pulmonary stenosis, mental retardation and similar facial appearance, Amer. ]. Cardiol., 13:471, 1964. 8 FRASER, D., KmD, B. S. L., KOOH, S. W., AND PAUNIER, L.: A new look at infantile hypercalcemia, Pediat. Clin. N. Amer., 13:503, 1966. 9 MEIUIITr, A. D., PALMER, C. G., LURIE, P. R, AND PETRY, E. L.: Supravalvular aortic stenosis: Genetic and clinical studies (abstract), ]. Lab. Clin. Med., 62: 995,1963. 10 LOGAN, W. F. W. E., JONES, E. W., WALKER, E.,
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12 13
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COULSHED, N., AND EpSTEIN, E. J., Familial supravalvular aortic stenosis, Brit. Heart. 1., 27:547, 1965. OTTEsEN, O. E., ANnA, A. U., AND ROWE, R. D.: Peripheral vascular anomalies associated with the supravalvular aortic stenosis syndrome, Radiology, 86:430, 1966. BOURASSA, M. G., AND CAMPEAU, L.: Combined supravalvular aortic and pulmonic stenosis, Circulation, 28: 572,1963. KURLANDER, G. J., PETRY, E. L., TAYBI, H., LURIE, P. R., AND CA~IPBELL, J. A.: Supravalvular aortic stenosis: Roentgen analysis of 27 cases, Amer. I. Roentgen., 98:782, 1966. GARCIA, R. E., FRIEDMAN, W. F., KABACK, M. M., AND ROWE, R. D.: Idiopathic hypercalcemia and supravalvular aortic stenosis, New Eng. 1. Med., 271:117, 1964. FRIEDMAN, W. F., AND ROBERTS, W. C.: Vitamin D and the supravalvular aortic stenosis syndrome: The transplacental effects of vitamin D on the aorta of the rabbit, Circulation, 34:77, 1966. FRIEDMAN, W. F.: Vitamin D as a cause of the supra-
17 18 19 20 21
valvular aortic stenosis syndrome, Amer. Hearl 1., 73: 718,1967. TAKEKAWA, S. D., KINCAID, O. W., TITUS, J. L., AND DUSHANE, J. W.: Congenital aortic stenosis, Amer. ]. Roentgen., 98:800, 1966. EBERLE, P., AND BEUREN, A. J.: Chromosome studies in patients with supravalvular aortic stenosis, Lancet, 2: 438,1963. JOSEPH, M. C., POUNI, P. E., AND GoLD, R. G.: Chromosome studies in patients with supravalvular aortic stenosis (Letter to the editor), Lancet, 2:788, 1963. GROUCHY, J. DE, AND EMERIT, I.: Chromosome studies in patients with supravalvular aortic stenosis (Letter to the editor), Lancet, 2:789, 1963. KAHLER, R. L., BRAUNWALD, E., PLAUTH, W. H., JR., AND MORROW, A. G.: Familial congenital heart disease: Familial occurrence of atrial septal defect with A-V conduction abnormalities; supravalvular aortic and pulmonic stenosis; and ventricular septal defect, Amer. 1. Med., 40:384, 1966.
Reprint requests: Section of Publications, Mayo Clinic, Rochester, Minnesota 55901.
OBSERVAnONS ON CAPILLARY AND VENOUS PULSE The presence of large and rapidly falling pulsations is demonstrated in an exquisite manner in insufficiency of the aortic valves. The manner of the appearance and disappearance of the capillary pulse, is objectively as characteristic a sign of aortic insufficiency as the exquisitely abrupt pulse is to the palpating finger. It is, generally, impossible to say in which finger nail is the phenomenon the most distinct, but it seems to occur
most frequently in the index finger. The white zone is usually found in the third quarter of the nail, measuring from the matrix, and the pulsation is at times more distinct in the lower part, at other times in the upper part. Quincke, H. (1842-1922) in Willius, F. A. and Keys, T. E.: Classics of Cardiology, (Vol. II) Dover Publications, New York, 1941
Postgraduate Course on Intensive Management of Respiratory Diseases Winnipeg, October 16-18, 1969
(See pages 441,442 this issue, for complete program)
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