Holt-Oram
Syndrome
in
A Case
Elderly History an
Patient—
Schwartz, M.D. Leibovitz, M.D. B. Berti, M.D. Y. Baumel, M.D.
J. A.
and B.
Habot, M.D.
BEER-YAACOV, ISRAEL
Abstract The authors present a typical case of Holt-Oram syndrome in an eightyyear-old woman. The patient had atrial-septal defect and phocomelia but was independent in the activities of daily living. Case
History
eighty-year-old, unmarried woman was admitted to our geriatric department in October, 1990, because of right hemiplegia. She was known to suffer from Holt-Oram syndrome (Figure 1), noninsulin-dependent diabetes mellitus, and congestive heart failure. She was bom in 1910 to healthy parents who gave birth to four children. Her twin brother, who suffered also from Holt-Oram syndrome (HOS), was so depressed from his illness that he committed suicide at the age of forty. Another sister died from cancer and another is healthy and has normal An
children. The patient told us that her mother took medicaments during her pregnancy. Until hospitalization the patient was completely independent in her activity of daily living and also had a hobby of painting. Pertinent findings on physical examination were: right flaccid hemiplegia; partial motor aphasia; bilateral phocomelia; atrial fibrillation; left upper ejection systolic murmur, grade 3/6; and congestive heart failure, mainly left. Computed tomography of the brain showed bleeding of the area of left basal ganglia. Doppler examination of the carotid arteries showed small plaques in the bifurcation of both From the "Shmuel-Harofe"
Hospital,
Geriatric Medical Center, Beer-Yaacov, Israel
706 Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
707
FIG. l. Holt-Oram
Syndrome
sides without
significant disturbance of blood flow. X-rays of the chest showed left ventricular hypertrophy with congestion of lungs. Electrocardiography showed atrial fibrillation, clockwise rotation, right-axis deviation, incomplete right bundle branch block, and signs of strain in leads I-III and aVF. Echo cardiography demonstrated a large atrial-septal defect (ostium secundum type) with left-to-right shunt, pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid and pulmonic regurgitation. The blood test yielded glucose in the range of 220-330 mg percent, which dropped to 155 mg percent after treatment with insulin. Other tests, including blood count and kidney and liver function tests, gave results in the normal ranges. The
patient
died because of
aspiration pneumonia
one
month after
hospitalization.
Discussion Holt-Oram syndrome is a genetically determined disorder in which congenital heart disease is associated with upper extremity anomalies.’ HOS is transmitted as an autosomal dominant disorder. Sporadic cases are common and represent new mutations . The skeletal anomalies are various and range from severe phocomelia to minimal carpal bone changes, visible only in radiographs. The carpal anomalies appear to be more specific of the syndrome than thumb
changes.3’4 Among other extracardiac anomalies are: aplastic anemia, calcaneus bile, myopia, melanopigmentation of the skin, and criss-cross asymmetry between clavicles and scapula.5 The most common congenital cardiac anomaly in this syndrome is the ostium secundum type of atrialseptal defect. Other defects that may occur are: ventricular septal defect, patent ductus arte-
Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
708
riosus, transposition of the great vessels, anomalous coronary arteries, ostium primum atrial-septal defect, aortic coarctation, pulmonary stenosis, pulmonary arterial branch stenosis, and persistent left superior vena cava . 6,1 We could not find in the literature another case of HOS reaching the ninth decade. There reports of patients reaching the ages of eighty-seven and ninety-four years with ostium secundum atrial-septal defect.’ The average age at death, in patients with unrepaired secundum atrial-septal defect, is thirty-nine to forty-nine years. If closure of the defect was done before the age of twenty-five, longevity was normal.9 Arms and hands are the instruments with which we accomplish basic activities. Our patient conducted normal life with normal activities of daily living although she had severe bilateral phocomelia. Surgery is currently being considered for reconstruction in these disabled paare case
tients.’3 A possible explanation for the patient’s stroke is that venous clots, undetectable by usual clinical methods, cross the patent foramen with resultant arterial embolization.’° Our patient represents the first case described in an elderly person. The patient was bom before Holt and Oram described the syndrome in 1960’ and also before the era of thalidomide.&dquo; Our patient was born to healthy parents and had a twin brother with the same syndrome. Conclusion The question whether their mother had taken therapeutic drugs during pregnancy or whether a spontaneous mutation caused the syndrome in both children remains unsolved. If it was a spontaneous mutation, then this is the first pair of twins having the mutagenic type of Holt-Oram syndrome.
J. Schwartz, M. D.
"Shmuel-Harofe" Hospital P.O.b 2 Beer-Yaacov 70300, Israel
References 1. Holt M, Oram S: Familial heart disease with skeletal malformations. Br Heart J 22:236-242, 1960. 2. Najjar H, Mardini M, Tabfaa R, et al: Variability of the Holt-Oram syndrome in Saudi individuals. Am J Med Genet 29:851-855, 1988. 3. Bartolomei B, Eng GD: The Holt-Oram syndrome: A case presentation and review of management parameters. Arch Phys Rehabil 68:41-45, 1987. 4. Poznanski AK, Gall JC, Stem AM: Skeletal manifestations of the Holt-Oram syndrome. Radiology 94 :4553, 1970. 5. Zlang KZ, Sun QB, Cheng TO: Holt-Oram syndrome in China: A collective review of 18 cases. Am Heart J 111:572-577, 1986. 6. Fowler NO: Cardiac Diagnosis and Treatment, ed 2,
1976, pp 851-852. 7. 8.
Cheng TO: Holt-Oram syndrome in a Puerto Rican family—case reports. Angiology 38:896-902, 1987. Perloff JK: Ostium secondun atrial-septal defect—sur-
vival for 87 and 94 years. Am J Cardiol 53:388-389, 1984. 9. Murphy JG, Gresh BJ, McGoon MD, et al: Long-term outcome after surgical repair of isolated atrial-septal defect. N Engl J Med 323:1645-1650, 1990. Anderson JL, et al: Clinically silent atrial-septal defects with evidence for cerebral emobolization. Ann Intern Med 105:695-697, 1986. 11. Smithells RW: Defects and disabilities of thalidomide children. Br Med J 1:269-272, 1973.
10.
Harvey JR, Teague SM,
Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
Syndrome
in
A Case
Elderly History an
Patient—
Schwartz, M.D. Leibovitz, M.D. B. Berti, M.D. Y. Baumel, M.D.
J. A.
and B.
Habot, M.D.
BEER-YAACOV, ISRAEL
Abstract The authors present a typical case of Holt-Oram syndrome in an eightyyear-old woman. The patient had atrial-septal defect and phocomelia but was independent in the activities of daily living. Case
History
eighty-year-old, unmarried woman was admitted to our geriatric department in October, 1990, because of right hemiplegia. She was known to suffer from Holt-Oram syndrome (Figure 1), noninsulin-dependent diabetes mellitus, and congestive heart failure. She was bom in 1910 to healthy parents who gave birth to four children. Her twin brother, who suffered also from Holt-Oram syndrome (HOS), was so depressed from his illness that he committed suicide at the age of forty. Another sister died from cancer and another is healthy and has normal An
children. The patient told us that her mother took medicaments during her pregnancy. Until hospitalization the patient was completely independent in her activity of daily living and also had a hobby of painting. Pertinent findings on physical examination were: right flaccid hemiplegia; partial motor aphasia; bilateral phocomelia; atrial fibrillation; left upper ejection systolic murmur, grade 3/6; and congestive heart failure, mainly left. Computed tomography of the brain showed bleeding of the area of left basal ganglia. Doppler examination of the carotid arteries showed small plaques in the bifurcation of both From the "Shmuel-Harofe"
Hospital,
Geriatric Medical Center, Beer-Yaacov, Israel
706 Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
707
FIG. l. Holt-Oram
Syndrome
sides without
significant disturbance of blood flow. X-rays of the chest showed left ventricular hypertrophy with congestion of lungs. Electrocardiography showed atrial fibrillation, clockwise rotation, right-axis deviation, incomplete right bundle branch block, and signs of strain in leads I-III and aVF. Echo cardiography demonstrated a large atrial-septal defect (ostium secundum type) with left-to-right shunt, pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid and pulmonic regurgitation. The blood test yielded glucose in the range of 220-330 mg percent, which dropped to 155 mg percent after treatment with insulin. Other tests, including blood count and kidney and liver function tests, gave results in the normal ranges. The
patient
died because of
aspiration pneumonia
one
month after
hospitalization.
Discussion Holt-Oram syndrome is a genetically determined disorder in which congenital heart disease is associated with upper extremity anomalies.’ HOS is transmitted as an autosomal dominant disorder. Sporadic cases are common and represent new mutations . The skeletal anomalies are various and range from severe phocomelia to minimal carpal bone changes, visible only in radiographs. The carpal anomalies appear to be more specific of the syndrome than thumb
changes.3’4 Among other extracardiac anomalies are: aplastic anemia, calcaneus bile, myopia, melanopigmentation of the skin, and criss-cross asymmetry between clavicles and scapula.5 The most common congenital cardiac anomaly in this syndrome is the ostium secundum type of atrialseptal defect. Other defects that may occur are: ventricular septal defect, patent ductus arte-
Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
708
riosus, transposition of the great vessels, anomalous coronary arteries, ostium primum atrial-septal defect, aortic coarctation, pulmonary stenosis, pulmonary arterial branch stenosis, and persistent left superior vena cava . 6,1 We could not find in the literature another case of HOS reaching the ninth decade. There reports of patients reaching the ages of eighty-seven and ninety-four years with ostium secundum atrial-septal defect.’ The average age at death, in patients with unrepaired secundum atrial-septal defect, is thirty-nine to forty-nine years. If closure of the defect was done before the age of twenty-five, longevity was normal.9 Arms and hands are the instruments with which we accomplish basic activities. Our patient conducted normal life with normal activities of daily living although she had severe bilateral phocomelia. Surgery is currently being considered for reconstruction in these disabled paare case
tients.’3 A possible explanation for the patient’s stroke is that venous clots, undetectable by usual clinical methods, cross the patent foramen with resultant arterial embolization.’° Our patient represents the first case described in an elderly person. The patient was bom before Holt and Oram described the syndrome in 1960’ and also before the era of thalidomide.&dquo; Our patient was born to healthy parents and had a twin brother with the same syndrome. Conclusion The question whether their mother had taken therapeutic drugs during pregnancy or whether a spontaneous mutation caused the syndrome in both children remains unsolved. If it was a spontaneous mutation, then this is the first pair of twins having the mutagenic type of Holt-Oram syndrome.
J. Schwartz, M. D.
"Shmuel-Harofe" Hospital P.O.b 2 Beer-Yaacov 70300, Israel
References 1. Holt M, Oram S: Familial heart disease with skeletal malformations. Br Heart J 22:236-242, 1960. 2. Najjar H, Mardini M, Tabfaa R, et al: Variability of the Holt-Oram syndrome in Saudi individuals. Am J Med Genet 29:851-855, 1988. 3. Bartolomei B, Eng GD: The Holt-Oram syndrome: A case presentation and review of management parameters. Arch Phys Rehabil 68:41-45, 1987. 4. Poznanski AK, Gall JC, Stem AM: Skeletal manifestations of the Holt-Oram syndrome. Radiology 94 :4553, 1970. 5. Zlang KZ, Sun QB, Cheng TO: Holt-Oram syndrome in China: A collective review of 18 cases. Am Heart J 111:572-577, 1986. 6. Fowler NO: Cardiac Diagnosis and Treatment, ed 2,
1976, pp 851-852. 7. 8.
Cheng TO: Holt-Oram syndrome in a Puerto Rican family—case reports. Angiology 38:896-902, 1987. Perloff JK: Ostium secondun atrial-septal defect—sur-
vival for 87 and 94 years. Am J Cardiol 53:388-389, 1984. 9. Murphy JG, Gresh BJ, McGoon MD, et al: Long-term outcome after surgical repair of isolated atrial-septal defect. N Engl J Med 323:1645-1650, 1990. Anderson JL, et al: Clinically silent atrial-septal defects with evidence for cerebral emobolization. Ann Intern Med 105:695-697, 1986. 11. Smithells RW: Defects and disabilities of thalidomide children. Br Med J 1:269-272, 1973.
10.
Harvey JR, Teague SM,
Downloaded from ang.sagepub.com at Glasgow University Library on June 26, 2015
