(Chest. 2001;119:1610-1612.)
© 2001
American College of Chest Physicians
Primary Spontaneous Pneumothorax in Two Siblings Suggests Autosomal Recessive Inheritance*
Pasi A. Koivisto, MD, PhD and
Aki Mustonen, MD, PhD
*
From the Department of Clinical Genetics, Tampere University Hospital, Tampere, Finland.
Correspondence to: Pasi A. Koivisto, MD, PhD, Department of Clinical Genetics, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland; e-mail: blpako{at}uta.fi
 |
Abstract
|
|---|
We report on a sister and brother with recurrent spontaneous
pneumothorax without underlying connective tissue disease and without
other affected relatives. The occurrence of spontaneous pneumothorax in
two siblings from a large Finnish family raises the possibility of
autosomal recessive inheritance of this disorder in some
patients.
Key Words: autosomal recessive • inheritance • spontaneous pneumothorax
|
Introduction
|
|---|
Primary
spontaneous pneumothorax is a rare disorder mostly occurring in male
subjects. Smoking, height (especially in male subjects), and family
history are the best known risk factors for primary spontaneous
pneumothorax. Most of the cases are sporadic, but it is also well known
that primary spontaneous pneumothorax may be inherited.1
Familial pneumothorax may be a complication of various inherited
disorders, such as 
1-antitrypsin deficiency,
Marfan’s syndrome, and the Ehlers-Danlos syndrome, but familial cases
without evidence of connective tissue disease do
occur.2
3
4
Primary spontaneous pneumothorax is genetically heterogeneous, and
articles published so far suggest autosomal dominant inheritance with
incomplete penetrance, polygenic, or X-linked recessive
inheritance.2
5
Only one report6
suggested
autosomal recessive inheritance.
Here, we report an observation of the occurrence of primary spontaneous
pneumothorax with a putative autosomal recessive transmission in a
large Finnish family.
|
Case Report
|
|---|
Patient 1
The index patient is the second child of healthy,
nonconsanguineous parents. She is 25 years old and a nonsmoker. She has
experienced attacks of diarrhea from the age of 14 years; generally,
the diarrhea has been related to eating disorders and anxiety, for
which she has been treated. Results of gastroscopy and colonoscopy have
remained normal. The age of menarche was 15 years, and no relationship
between primary spontaneous pneumothorax and menstruation was present.
She has not had pelvic pain, and findings of gynecologic examinations,
including transvaginal ultrasound, have remained normal. From the age
of 17 years, she has experienced spontaneous pneumothorax three times
in the left and right lungs. A left-sided pneumothorax developed when
she was 19 years, and because of slow resolution, it was treated with
plication of the bleb and pleurodesis. Reoperation was needed 2 years
later when the apical segment of the left lung was removed. The
histologic diagnosis of the removed lung tissue was inconclusive. At
the age of 21 years, the patient was examined for episodes of headache.
Neurologic findings and EEG and head CT results were normal. The last
attack of pneumothorax occurred at the age of 23 years, when
high-resolution CT showed one solitary bulla (diameter, 1 x 2.5 cm)
in the left lung. Spontaneous remission occurred. Ultrasound findings
of the patient’s upper abdomen and heart were normal. Her
ophthalmologic status was also normal. Blood levels of
1-antitrypsin were within reference values
(2.09 g/L), and the phenotype was MM.
At the age of 24 years, when she was 161 cm tall and weighed 42 kg, the
patient was examined by a clinical geneticist. No clinically
significant dysmorphic features were noted. Arachnodactyly was not
noted. Her elbow joints were slightly hypermobile, but other joints
were of normal mobility. The thorax was symmetrical, but her thoracic
spine was slightly scoliotic. Striae or varicose veins were not
seen. The teeth and palate were normal, and her skin was not
hyperelastic.
Patient 2
Patient 2 is a younger brother of the index patient. He is 21
years old and has been smoking for 4 years. His development was normal.
He has not had GI or neurologic symptoms. At the age of 17 years, a
spontaneous pneumothorax of the left lung was treated with drainage.
Two years later, a pneumothorax occurred on the left lung after minor
trauma. Spontaneous remission followed. At the age of 20 years, a
spontaneous pneumothorax developed on the same side. Because the
resolution was slow, thoracoscopic bullectomy was needed. A
pneumothorax recurred 2 months later and was again treated operatively
(thoracoscopic pleural abrasion and pleurodesis). The blood
1-antitrypsin level was within reference
values (1.6 g/L), and the phenotype was MM. High-resolution CT of the
lungs showed a few small subpleural bullae. Ultrasound findings of the
patient’s upper abdomen were normal. Echocardiography showed evidence
of a bicuspid aortic valve and mild regurgitation, but no aortic root
dilatation was seen. His ophthalmologic status was also normal.
At the age of 21 years, when he was 183 cm tall and weighed 62 kg, the
patient was seen by the clinical geneticist. No minor anomalies were
seen. Joints were of normal mobility. The thorax was symmetrical, and
scoliosis was not noticed. Striae or varicose veins were not seen. His
teeth and palate were normal, and his skin was not hyperelastic.
|
Discussion
|
|---|
Since the first description of primary spontaneous pneumothorax
> 50 years ago, the best-characterized mode of inheritance is
autosomal dominant with reduced penetrance in female subjects. However,
one report suggested autosomal recessive inheritance in primary
spontaneous pneumothorax. Gibson6
described three sisters
with repeated pneumothoraces beginning at 28 years, 32 years, and 37
years of age, respectively.
We report here two siblings with spontaneous pneumothorax with probable
autosomal recessive inheritance. Bullae were seen in both patients, and
pneumothorax episodes most likely resulted from a rupture of a bulla.
Because bullae and spontaneous pneumothorax are known complications in
the Marfan’s syndrome and Ehlers-Danlos syndrome, as well as in
1-antitrypsin deficiency, the possibility of
these connective tissue diseases was carefully excluded. In addition,
because of the slightly atypical clinical course of primary spontaneous
pneumothorax in patient 1, several nongenetic etiologies of primary
spontaneous pneumothorax, such as endometriosis, were excluded.
None of their many relatives had a history of pneumothorax or any
symptoms or signs of pulmonary or connective tissue disease. In
addition, chest radiographs of the affected siblings’ parents showed
no indication of any abnormality, and the patients were not taller than
their first-degree relatives, which further strengthens the likelihood
of autosomal recessive inheritance in this family (Fig 1
). Determination of human leukocyte antigen haplotypes of the patients
could have been of some importance in evaluating the inheritance of
primary spontaneous pneumothorax in the family because an association
between human leukocyte antigen haplotype A2B40 and primary spontaneous
pneumothorax has been demonstrated.7
However, the patients
refused genetic testing.
View larger version (10K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1.. Representation of a large Finnish pedigree
including the clinically described patients. Clear circle = woman;
clear square = man; black circle = woman with spontaneous
pneumothorax; black square = man with spontaneous pneumothorax; slash
through symbol = deceased; line above symbol = personally examined
patient; arrow = index case.
|
|
The experiences of the family reported here strongly suggest autosomal
recessive inheritance of primary spontaneous pneumothorax. X-linked
recessive transmission is ruled out because of an affected female
family member. Excluding autosomal dominant inheritance is more
difficult. However, recurrent pneumothorax rarely remains undiagnosed,
and because neither the parents nor any other relatives of the patients
have had primary spontaneous pneumothorax, autosomal recessive is the
most likely mode of inheritance. Consistent with the possibility
of autosomal recessive inheritance is that consanguinity is common in
the area from which the patients and their ancestors originate. The
grandparents of the patients were traced back to the late 19th century.
Until this period, they were unrelated, but a common ancestor is highly
likely because this sparsely populated rural area was gradually
inhabited in the 17th century by a small number of people.
Received for publication April 25, 2000.
Accepted for publication November 9, 2000.
|
References
|
|---|
-
Melton, LJ, Hepper, NG, Offord, KP (1979) Incidence of spontaneous pneumothorax in Olmsted County, Minnesota: 1950 to 1974. Am Rev Respir Dis 120,1379-1382[ISI][Medline]
-
Abolnik, IZ, Lossos, IS, Zlotogora, J, et al (1991) On the inheritance of primary spontaneous pneumothorax. Am J Med Genet 40,155-158[CrossRef][ISI][Medline]
-
Boyd, DHA (1957) Familial spontaneous pneumothorax. Scot Med J 2,220-221
-
Yellin, A, Shiner, RJ, Lieberman, Y (1991) Familial multiple bilateral pneumothorax associated with Marfan syndrome. Chest 100,577-578[Abstract/Free Full Text]
-
Wilson, WG, Aylsworth, AS (1979) Familial spontaneous pneumothorax. Pediatrics 64,172-175[Abstract/Free Full Text]
-
Gibson, GJ (1977) Familial pneumothoraces and bullae. Thorax 32,88-90[Abstract]
-
Sharpe, IK, Ahmad, M, Braun, W (1980) Familial spontaneous pneumothorax and HLA antigens. Chest 78,264-268[Abstract/Free Full Text]
TOP
Abstract
Introduction
