Download Congenital Heart Disease in a Tetra-X Woman

axis shift in the frontal plane from right axis deviation to
left axis deviation (Fig 1B). Similar axis changes have
been reported following resection of a ventricular
aneurysm.16 It is not clear whether the shift is due to
left anterior hemiblock or due to removal of electrically
inert muscle. Since the cardiac silhouette had returned
to near normal postoperatively, the axis shift was not due
to unusual position of the heart.
We have shown that regurgitation into a false aneurysm must be included in the H e r e n t i a l diagnosis of
apical systolic murmur in a patient with a previous
history of a myocardial infarction. Other explanations
include a ventricular septa1 defect and mitral insufficiency. Because of the high incidence of rupture of false
ventricular aneurysms surgery should be considered
when the diagnosis is established. Surgical resection can
eliminate a potential cause of sudden death.
1 Dubnow MH, Burchell HB, Titus JL: Postinfarction ventricular aneurysm. A clinicomorphologic and electrocardiographic study of 80 cases. Am Heart J 70:753-760,
1965
2 Luisada AA, Argano B: F'honocardiography. Bizarre
murmurs in a case of ventricular aneurysm. Dis Chest
55:489-491, 1969
3 Harvey WP, Mandanis JP: Ausculatory findings in pericardial effusion and in ventricular aneuysm. Circulation
18: 1034-1037, 1958
4 Scherf D, Brooks AM: The murmurs of cardiac aneurysm.
Am J Med Sci 218:389-398, 1949
5 Roberts WC, Morrow AG: Pseudoaneurysm of the left
ventricle. An unusual sequel of myocardial infarction and
rupture of the heart. Am J Med 43:639-644, 1967
6 Chesler E, Korns ME, Semba T, et al: False aneurysms of
the left ventricle following myocardial infarction. Am J
Cardiol23:76-82, 1969
7 Gobel FL, Visudh-Arom K, Edwards JE: Pseudoaneurysm of the left ventricle leading to recurrent pericardial hemorrhage. Chest 59:23-27, 1971
Pseudoaneurysm of the
8 Hurst CO, Fine G, Keyes JW:
heart. Report of a case and review of the literature.
Circulation 28:427-436, 1963
9 Cone RB, Hawley RL: Pseudoaneurysm of the heart
following infarction. Arch Path 77: 168-171,1964
10 Bhornsson L: Pseudoaneurysm of the left ventricle of the
heart. A rare complication of myocardial rupture following infarction-report of a case. Am J Clin Path01 41:302306,1964
11 Ersek RA, Chesler E, Korns ME, et al: Spontaneous
rupture of a false left ventricular aneurysm following
myocardial infarction. Am Heart J 77:877880,1969
12 Vieweg WVR, Thompson ME, McHale JJ, et al: Ventricular tachyarrhythmias controlled by ventricular
aneurysmectomy and aortocoronary-saphenous vein bypass grafts. Report of a case. Med Ann DC 41:565-567,
1972
13 Van Tassel RA, Edwards JE: Rupture of heart complicating myocardial infarction. Analysis of 40 cases including
nine examples of left ventricular false aneurysm. Chest
61:104-116, 1972
14 Likoff W, Bailey CP: Ventriculoplasty: excision of myocardial aneurysm. Report of a successful case. JAMA
158:915-920, 1955
15 Smith RC, Goldberg H, Bailey CP: Pseudoaneurysm of
the left ventricle: diagnosis by direct cardioangiography.
Surgery 42:49&510, 1957
16 Cokkinos DV, Hallman GL, Cooley DA, et al: Left
ventricular aneurysm: analysis of electrocardiographic
features and postresection changes. Am Heart J 82:149157, 1971
Congenital Heart Disease in a
John F . Keane, M.D.; James E . McLennan, M.D.; Je G . Chi,
M.D.; Virginia Monedjikooa, M.D.; Cordon F . Vawter,
M.D.; Floyd H. GiUes, M.D.; and Richard Van Praagh,
M.D.
This is the 21st reported case of tetmX, the oldest patient (58 years) to date, the first studied at autopsy, and
the f h t with documented congenital heart disease. Her
mental retanlation may weU have been related to wide
spread deficiency of bemispheral white matter. Death
resulted from multiple atrial septal defects.
T
etra-X is a rare abnormality of the sex chromosomes;
only 20 cases have been reported pre~iously.l-~'J
It
is thought to result from nondisjunctions during the first
and second meiotic divisions of oogenesis.Z0 The clinical features are nonspecific and have included
mental retardation,~~~-~~~1~~~0
reduction of dermal
ridges,l7?lg behavioral disturbance^,^^^^^ hypertelorism
with epicanthal fold~,S-~
eye anomalies ( m y ~ p i a , ~ ~ ' ~
nystagmus,17 iridoschisislO~l~), skeletal abnormalities (clinodactyly,~'J~~~~1*~~0
radioulnar
syn0stosis,l7.2~ dislocation of the hip,* tall stature8),
menstrual irregularities with reduced fertility,zo and
congenital heart disease.l0~l1
The patient to be presented is the &st case of tetra-X
to be studied at autopsy and the first with documented
congenital heart disease.
The patient was a mentally retarded woman with an IQ of
50, cardiomegaly, a systolic ejection murmur in the pulrnonary area, and accentuation of the second heart sound with
wide splitting (60 msec). Menses and menopause (at 42
years ) were unremarkable.
The clinical picture of congestive heart failure appeared
when the patient was 52 years of age and progressed inexorably.
Chest x-ray examinations revealed cardiomegaly, dilatation
of the main pulmonary artery and proximal branches, "pruning" of the smaller pulmonary arteries, and reduced periph'From the De artments of Cardiology, Neurology, and Pathology, Chiden's Hos ital Medical Center, and the De artments of Pediatrics an%~athology,Harvard Medical ~ J o o l ,
Boston, and Wrentham State School, Wrentham, Mass.
This work was supported in part by Grants HL-10436-06 and
5-T01-HLD58.55-04 from the Heart and Lun Institute, National Institutes of Health, Bethesda, Md., %y the United
Cerebral Palsy Research and Educational Foundation ( R22489), by Pro am F'mject No. NSI-EP, 1 PO1 NS 0970401 NSPA, HD, P$;NDs, and by the Children's Hospital Medical Center Mental Retardation and Human Development
Research Program ( HD 03-0773 ) , NICHD.
R rint requests: Llr. Van Praagh, Children's Hospital MediJ c e n t e r , Boston 021 15
CHEST, 66: 6, DECEMBER, 1974
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6- 12 and X (C)
FIGURE
1. Chromcwomal preparation showing two extra pairs of C group chrom~somesindicating
a 48, XXXX chromosomal constitution.
RPA
F
IPA
FIGURE
2. Specimen of heart and left lung. a External frontal view showing the normally interrelated right atrium ( RA ), left atrium ( LA ), right ventricle ( RV ), left ventricle ( LV ), dilated
main pulmonary artery ( MPA) and left pulmonary artery ( LPA). b. Interior of the RA showing
the three secundum type of atrial septal defects ( ASD II), with the superior vena cava ( SVC),
right atrial appendage (RAA) and tricuspid valve (TV) for orientation. c. Opened RV and
MPA. Note the hypertrophy and enlargement of RV and the dilatation of the MPA. The
right pulmonary artery (RPA) is unopened. The pulmonary valve is bicuspid, calcified, and regurgitant, but not stenotic. d. Interior of Lh showing the deficiency and fenestrations
of septum primum, the flap valve of the foramen male, resulting in three ASD 11. Left pulmonary
veins ( LW ) , right pulmonary veins ( RPV ), and left atrial appendage ( LM ) provide orienta.
tion. Ruler is marked in cm and mm.
CHEST, 66: 6, DECEMBER, 1974
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CONGENITAL HEART DISEASE IN A TETRA-X WOMAN 727
.-.
,
..
' . :>
.
J
\
'
r.
.
I
,
-
-
C
FIGURE
3. Brain, a. Coronal sections of tetra-X female's brain showing a generalized reduction of
hemispheral white matter. b. A control, sectioned similarly. c. Low power, and d, high power
histologic sections ( Holzer method) showing glial fibrils spread diffusely throughout hemispheral
white matter.
eral pulmonary vascularity-findings consistent with pulmonary vascular obstruction. El-diograms
revealed atrial
fibrillation, right axis deviation, and marked right ventricular
hypertrophy.
Buccal smear showed that 28 percent of the cells examined
were chromatin positive, 18 percent having two Barr bodies
and 10 percent having three Barr bodies. Karyotype (Fig 1)
indicated a 48, XXXX chromosomal constitution: of 80 cultured peripheral leukocytes examined, there were 56 (93.3
percent) with 48, XXXX, two (3.3 percent) with 47, XXX,
and two (3.3 percent) with 46,XX.
The patient died at 58 years from congestive heart failure.
Autopsy si~owedcardiomegaly (5301270 m),with hypertrophy and enlargement of the right atrium and right ventricle, and dilatation of the main pulmonary artery (Fig 2ac ) . Three atrial septa1 defects of the ostium secundum type
measured 2.2 X 1.7, 1.3 x 0.8, and 0.6 x 0.3 c m (Fig 2b, d ) .
The pulmonary valve was bicuspid, calcified and regurgitant.
Grade 2 pulmonarv vascularobstructive changes were found
histologically.21 A n t e m o m mural thrombi were found in
both atria (chronic atrial fibrillation) and organized t h m boemboli were present in two s m d branches of the right
pulmonary artery.
The brain was underweight ( 1050/1250 grn). without
obvious external abnormality. However, coronal d o l l s revealed a generalized deficiency of hemispheral white matter
( Fig 3a) compared with normal controls (Fig 3b). Paucity of
728 KEANE ET A 1
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white matter was least marked in the temporal lobes. Interhemispheral association pathways such es the corpus callosum were thin. The ventricles were mildly enlarged (Fig
3a). The pyramidal system was small bilaterally. The only
histologic abnormality was widespread fibrillary gliosis of
hemispheral white matter (Fig 3%d).
DISCUSSION
Our patient is the first case of tetra-X in whom congenital heart disease has been documented. However, a
clinical diagnosis of patent ductus arteriosus, not confinned by catheterization, was made in one previously
reported patient.lO.1l Available data1-2O suggest that
congenital heart disease is not characteristic of the tetra(2 of 21 -,
9.5 percent).
The widespread deficiency of cerebral white matter
found in
patient,
not
for
to be a basis for her
reducing association P ~ ~ W Y(corti-rtical,
S
thalamocortical, and interhemispheral).
ACKNOWLEDGMENTS: We thank MR. Ingefelde Lukk of
Laboratof the Wrentham State School
the C ~ ~ o s o m
e
for the cytogenetic preparations, Mr. Terence Wrightson for
otography, Miss Donna Farina for art work and Miss
leanor M d o u s k i for secretarial assistance.
&h
CHEST, 66: 6, DECEMBER, 1974
1 Carr DH, Barr ML, Plunkett ER: An XXXX sex chromosome complex in two mentally defective females. Canad
Med Assoc J 84: 131-137, 1961
2 Bergemann E: Manifestation familiale du karyotype
triplo-X-communication prkliminaire. J G d t Hum 10:
370371, 1962
3 Bergemann E: Die Haufigkeit des Abweichens von
normalen Geschtschromatin und eine Familienuntersuchung bei Triplo-X. Helv Med Acta 29:420-422, 1962
4 Davies TS: Buccal smear s w e y s for sex chromatin. Br
Med J 1:1541-1542, 1963
5 Lejeune J, Abonyi D: Syndrome 48, XXXX chez une We
de quatorze ans. Ann G d t 11: 117-119, 1968
6 de Grouchy J, Grissand HE, Richardet JM, et al: Syndrome 48, XXXX chez une enfant de six ans. Transmission
anormale du group Xg. Ann G 6 d t 11:120-124, 1968
7 DiCagno L, Franceschini P: Feeblemindedness and
XXXX karyotype. J Ment Defic Res 12:226-236, 1968
8 Konishi S, Yanagisawa S: A case of an XXXX sex chrornosome complex. Cong Awm 8:211-218, 1968
9 Anderton RE, McLendon WW, Ford EL, et al: Two extraX chromosomes found in a teen-age girl. Hosp Tribune
2:30,1968
10 Sokolowski J, Knaus A, Kleczkowska A: Dermatoglyphics
of two cases of X-tetrasomy. Am J Hum Genet 21:559565, 1969
11 Halikowski B, Kleczkowska A, Coscinska Z, et al: "Superfemale" syndrome in a 12-year-old girl (XXXX sex
chromosome arrangement associated with a combination
of congenital abnormalities). Ped P d 44:1147-1154, 1969
12 Hanicka M, Kleczkowska A, Makowska J, et al: Iridoschisis in a girl with karyotype 48, XXXX. Pol.Tyg Lik
24: 1164-1160, 1969
13 Berkeley MIK, Faed MJW: A female with the 48, XXXX
karyotype. J Med Genet 7:83-85,1970
14 Remck EC: Mosaic X W X X X X sex chromosome complement. Case report and review of literature. J Ment
Defic Res 14:141-148, 1970
15 Park IJ, Tyson JE, Jones HW: A 48, XXXX female with
mental retardation. Report of a case. Obstet & Gyn 35:
248-252, 1970
16 Duncan BP, Nicholl JO, Downes R: An XXXX sex
chromosome complement in a female with mild mental
retardation. Canad Med Assoc J 102:969-970, 1970
17 Telfer MA, Richardson CE,Helmken J, et al: Divergent
phenotypes among 48, XXXX and 47, XXX females. Am
J Hum Genet 22:326-335, 1970
18 Blackston RD, Chen ATL: A case of 48, XXXX female
with normal intelligence. J Med Genet 9:230-232, 1972
19 Remck EC: A female with XXXX sex chromosome complement. J Ment Defic Res 16:84-89, 1972
20 Cardner RJM, Veale AMO, Sands VE, et al: XXXX
syndrome: case report, and a note on genetic coum+hg
and fertility. Humangenetik 17:323-330, 1973
21 Heath D, Edwards JE: The pathology of hypertensive
pulmonary vascular disease. A description of six grades of
structural changes in the pulmonary arteries with special
reference to congenital cardiac septal defects. Circulation
18:533-547,1958
CHEST, 66: 6, DECEMBER, 1974
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Association of Holt-Oram Syndrome
and ~ ~ m ~ h o s a r c o r n a *
Bijan Nik-Akhtar, M.D., F.C.C.P.;OO Maniieh Khakpour,
M.D.;? Mohamod AU Rashed, M.D.;$ and Fatblah Hakami.
M.D.,F.C.C.P.$
Association of Holt-Oram syndrome and malignancy has
not been emphasized previously. Among reported cpses
only two such examples ex&. Based upon the fact that in
oar patient deficiency in immunogbbulins and impaired
cellular immunity co-existed, which we thought could pndispose to malignancy, and since in previous reported
cases impaired cellular immunity and diminished immMogbbulins were not reported, we suggest that this
association may not be only coincidentsl.
T
he Holt-Oram syndrome associated with lymphosarcoma, and coexistence of malignancy was demonstrated by our patient whom we report.
A 24-year-old right handed man was admitted to the
university hospital on October 5, 1970 because of paraplegia
for about two months. Physical examination on admission
revealed that he was chronically ill, cachectic and markedly
anemic. His chest was symmetrical on expansion and cardiac
apex was observed in sixth left interspace. His left arm was
10 an shorter than right arm and there was m p l e t e absence
of left thumb and fifth finger and marked limitation of
pronation and supination of the left hand.
On palpation, a few small adenopathies were felt in the
cervical, subaxillary and inguinal areas bilaterally. These
adenopathies were discrete, not tender and movable. In the
abdomen, the spleen was palpable 4 cm and the liver was 3
cm below left and right costal margins respectively. They
were smooth and not tender on palpation.
On percussion, heart was enlarged on both sides and no
thrill was palpable. On auscultation, the lungs were clear, but
cardiac auscultation revealed that the first heart sound was
normal while the second sound was persistently split with an
accentuated pulmonic component. A grade 3/6 scratchy
ejection systolic murmur was noted.
Roentgenogram of the chest revealed prominent main and
right pulmonary artery segments and increased pulmonary
vascular markings. The electrocardiogram revealed evidence
of right ventricular hypertrophy. The pulse rate was 80/min,
the blood pressure 160/85 mm Hg and his temperature was
38°C. The jugular venous pressure was normal with prominent "a" and "v" waves. Cardiac catheterization confirmed
the presence of an atrial septal defect with a moderate left-toright shunt and moderate pulmonary hypertension (Table
1).
Labordgl Data
.
Urine contained +1 protein and on microscopic examina-
*From the School of Medicine and S c h d of Public Health,
University of Tehran, Tehran, Iran.
OOAssociateProfessor of Medicine and Head, Deparbnent of
Medicine.
?Assistant Professor of Public Health.
$Associate Professor of Medicine.
§Assistant Professor of Cardiovascular and Thoracic Surgery.
Reprtnt requests: Dr. Nik-Akhtar, 127 Nadershah A m w ,
Near Bank MeUf Iran, Teheran, Iran
HOLT-ORAM SYNDROME AND LYMPHOSARCOMA 729