Download Pulmonary atresia with intact ventricular septum

American Journal of Medical Genetics 42:304-306 (1992)
Brief Clinical Report
Pulmonary Atresia With Intact Ventricular Septum
and Hypoplastic Right Heart in Sibs: A Single Gene
Disorder?
~~
David Chitayat, Nathalie McIntosh, and Jean-Claude Fouron
Department of Pediatrics, Division of Medical Genetics (D.C., N.M.), The Montreal Childreds Hospital, and The
Center for Human Genetics, McGill University (D.C., N.M.); Department of Pediatrics, Division of Cardiology,
Universite' de Montre'al and Hbpital Ste. Justine (J.-C.F.), Montreal, Quebec, Canada
We report on 2 sisters with hypoplastic right
heart and pulmonary atresia. The first sib
was found to have pulmonary atresia, intact
ventricular septum, and hypoplastic right
heart after delivery. Fetal echocardiography
at 22 weeks of gestation during the second
pregnancy documented the same cardiac abnormalities.Autopsy findings in the fetus confirmed the echocardiographic findings. No
other malformations were detected in either
case, and no other affected relatives were
identified. We suggest that this rare congenital heart defect may,in some cases, be an autosoma1 recessive trait.
intact interventricular septum, hypoplastic right heart
(HRH), and normal tricuspid valve. To our knowledge,
this is the first report of sibs being affected in this manner suggesting autosomal recessive inheritance, although multifactorial inheritance cannot be excluded.
CLINICAL REPORTS
Patient 1
The proposita, a girl, was the result of the first pregnancy of a 29-year-old, gravida 1 mother of Greek descent, and a 26-year-old father of Italian origin. Both
parents were healthy, nonconsanguineous, and their
family history did not reveal any relative with CHD. On
their physical examination no cardiovascular abnormality was noted. The mother denied having had viral infecKEY WORDS: congenital heart defect, multition or skin rash, exposure to medications, or ingestion of
factorial determination, fetal
alcoholic beverages, during the pregnancy. Pregnancy
was complicated by gestational diabetes detected at 28
echocardiography, hypoplastic right heart, autosomal reweeks of gestation which subsequently responded well
to diet modification.
cessive inheritance
Results of fetal ultrasounds at 3, 5, and 7 months
gestation were apparently normal, and fetal movements, first felt at 4% months of gestation, were, in
INTRODUCTION
retrospect, weak compared to those in the second pregThe prevalence of congenital heart defects (CHD) is nancy. Due to the lack of progression during labour,
4-8/1,000 [Ferencz et al., 19851.Familial occurrences of delivery was by uncomplicated Cesarean section. Apgar
almost all forms of CHDs have been reported, and most scores were 7 and 8, at 1and 5 min, respectively. On the
are thought to be multifactorially determined. However, first day of life the baby had perioral cyanosis and mild
monogenic inheritance with autosomal recessive and respiratory distress and was found to have a HRH with
dominant modes of transmission have also been postu- PA. On the second day of life she underwent an operation
lated and documented in a few cases (atrial septa1 de- for a central aortopulmonary shunt, during which she
fect, idiopathic hypertrophic subaortic stenosis, etc.) had 4 episodes of ventricular fibrillation and died 2 hr
[Lynch et al., 1978; Pare et al., 19611.
afterward. Autopsy confirmed a hypoplastic right venWe report on 2 sisters with pulmonary atresia (PA), tricle, atresia of the pulmonary valve, with stenosis of
the distal main pulmonary artery, and a patent ductus
arteriosus (Fig. 1).The right atrium contained a membrane
located above the coronary sinus which appeared
Received for publication January 22, 1991; revision received
to be continuous with the normal eustachian valve and
June 3, 1991.
Address reprint requests to Dr. D. Chitayat, Division of Medical may have obstructed the flow to the tricuspid valve. No
Genetics, The Montreal Children's Hospital, 2300 Tupper St., other abnormalities were detected; chromosomes were
normal (46,XX).
Montreal, Quebec, H3H 1P3, Canada.
0 1992 Wiley-Liss, Inc.
Hypoplastic Right Heart
Fig. 1. Cardiac autopsy in patient 1 showing hypoplasia of the right
ventricle (RV) with atresia of the pulmonic valve and narrow pulmonary artery (P). The left ventricle (LV) is well developed (L, lung).
Patient 2
The couple embarked on a second pregnancy a year
after the death of patient 1.The pregnancy was uncomplicated and repeat fetal ultrasounds were apparently
normal. However, a fetal echocardiograph a t 22 weeks of
gestation showed HRH and PA (Fig. 2). The couple chose
to terminate the pregnancy. Autopsy confirmed PA with
an intact ventricular septum, HRH, and patent foramen
ovale and PA. No other abnormalities were detected.
DISCUSSION
CHDs are heterogeneous and previous family studies
have suggested that 90% are apparent multifactorial
traits, 5%are due to a chromosome abnormality, and 3%
are due to a single gene disorder [Nora and Meyer, 1966;
Nora and Nora, 1983; Nora and Wolf, 19761. However,
305
more recent studies have shown that extracardiac malformations occur in approximately 27% of live-born patients with structural CHD, among them 13%with a
chromosome abnormality (including 10.4% with Down
syndrome), 4.6% with a recognized syndrome or single
gene defect, 1.0%had a suspected syndrome, and 8.3%a
nonsyndromal malformation [Ferencz et al., 19891.
Right ventricular hypoplasia with a normal tricuspid
valve is a rare congenital heart defect that is classified
into two types: the most common type with a hypoplastic, muscular right ventricle and stenotic or atretic pulmonary valve (type I), and a more rare type with a thin
and flabby right ventricular wall (type 11) [Taussig,
19601.Our patients exhibits type I. Interestingly, one of
the cases reported by Taussing [19601 under type I had a
membrane in the left auricle that partially obstructed
the mitral valve, similar to the membrane in the right
auricle of our Patient 1.The significance of this finding
is not known. We think that type I is the result of a right
ventricular outflow obstruction (severe pulmonary stenosis or atresia) while type I1 is the result of an intrinsic
abnormality in the right ventricular wall. When the
pulmonary atresialstenosis is associated with an intact
ventricular septum, the blood from the right atrium
ultimately must cross the atrial septum to the left
atrium. The consequent elevation in the right ventricular pressure results in hypertrophy of the right ventricular wall and a decrease in the right ventricular
volume.
PA with an intact interventricular septum, found in
our patients, is a rare malformation first reported by
Hunter in 1783 [cited in Gutgesell, 19901.It accounts for
only 3-4% of cases of CHD diagnosed in the first year of
life [Fyler, 1980; Gutgesell et al., 19821 and has an
incidence in livebirths ranging from 1/8,016 [Mitchell et
al., 19111 to 1/144,000 [Fyler, 19801. With this heart
defect, the right ventricle, as well as the tricuspid valve,
are usually smaller than normal [Van Praagh et al.,
1976; Zuberbuhler and Anderson, 19791. Van F’raagh et
al. [1976]noted marked hypoplasia of the right ventricle
Fig. 2. Fetal echocardiography of patient 2 showing hypoplastic right heart.
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Chitayat et al.
in 50%,moderate hypoplasia in 26%,and a normal right
ventricle in 10% of their cases. Thus, the hypoplastic
right heart is probably a secondary abnormality resulting from the right ventricular outflow obstruction in the
presence of the intact interventricular septum, rather
than a primary abnormality in the development of the
right ventricle. The normal structure of the aortic and
tricuspid valves and the complete closure of the ventricular septum show that the obstruction of the pulmonary valve occurs at the 25-mm stage (eighth week of
gestation), after the ventricular septum and aorticopulmonary septum have been formed.
To our knowledge this is the first report of PA, HRH,
intact ventricular septum, and normal tricuspid valve in
sibs (a father and son reported with PA, also had VSD
and thus do not belong in the same category as our
patients [DiChiara et al., 19801). Although multifactorial determination cannot be ruled out, the rarity of
the cardiac lesion found in our patients, coupled with the
recurrence of the exact lesion in sibs suggests autosomal
recessive inheritance.
The prognosis of this abnormality is very poor; only
33% of affected infants survive their first birthday
[Flyer et al., 19801. Our ability to diagnose this abnormality by fetal echocardiography provides families with
an important method for early detection of this severe
defect.
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