Ultrasound Obstet Gynecol 2012; 40: 724–729 Published online in Wiley Online Library (wileyonlinelibrary.com).
Letters to the Editor
Recurrent prenatally diagnosed isolated bilateral pulmonary agenesis We report a case of prenatally diagnosed pulmonary agenesis which recurred twice, providing evidence of a genetic origin of the disease. A 30-year-old woman, gravida 3 para 1, was referred for a second-trimester ultrasound examination. In 2004 the patient had undergone medical termination of pregnancy at 26 weeks of amenorrhea for pulmonary agenesis, but there was no further relevant family history and no consanguinity with her husband. In 2007 she had given birth to a healthy female. During this, her third, pregnancy the first-trimester ultrasound examination revealed no abnormalities. At 23 weeks of amenorrhea, a morphological ultrasound examination showed the heart to be occupying almost the entire thoracic cavity. The cardiac axis was slightly deviated and the thymus was well visualized but appeared ‘spread out’ (Figure 1a). Neither pulmonary arterial bifurcation nor pulmonary veins were identified. On parasagittal slices, the diaphragm was elevated bilaterally, and the trachea could not be visualized (Figure 1b). No other anomaly was detected. Based on these findings, bilateral pulmonary agenesis was suspected. The diagnosis of bilateral pulmonary agenesis was confirmed by a second ultrasound examination conducted by an expert. Given the poor prognosis, the couple requested medical termination of the pregnancy. A male fetus weighing 706 g was expelled at 25 weeks of amenorrhea. The fetal karyotype was 46,XY. Pathological examination of the fetus showed varus deformity of the feet, with discrete cutaneous webs across the base of the fingers. The penis was short and curved
downwards, with an anterior hypospadias. Complete absence of both lungs and trachea was confirmed, and there was no pulmonary vein into the left atrial cavity. Chromosomal analysis of fetal tissue showed a 700-kb heterozygotic inherited paternal 7q36.3 duplication. Parental karyotypes were normal. In 2011 the woman was referred for ultrasound examination at 12 weeks of amenorrhea for her fourth pregnancy. Once again, no pulmonary structure was observed. A diagnosis of pulmonary agenesis was confirmed on pathological examination after medical termination of pregnancy. The fetal karyotype was 46,XX. Pulmonary agenesis is a very rare condition resulting from failure of bronchial buds to develop1 – 4 . The prognosis for unilateral pulmonary agenesis is linked to the presence of concomitant morphological anomalies, whereas bilateral pulmonary agenesis is a fatal condition2 . This is the first report of antenatal diagnosis of multiple recurrences. Until now, bilateral pulmonary agenesis was thought to occur sporadically. The exact etiology is unclear, although genetic factors, viral infections and deficiencies in folic acid and vitamin A have been suggested as contributing factors3,4 . This anomaly arises very early in development, since the trachea appears as a ventral endodermal diverticulum budding from the foregut at approximately 26 days postconception. The pattern of growth is largely determined by the mesoderm, involving Hox genes and growth factors5 . On prenatal ultrasound examination, initial indicators of pulmonary agenesis include decreased thoracic volume, elevated diaphragm and cardiac axis deviation with a thoracic cavity largely occupied by the heart. Color Doppler scans reveal the absence of pulmonary arterial vessels. The thymus occupies the space where
Figure 1 (a) Axial view of fetal thorax at 23 weeks’ gestation showing absence of pulmonary tissue and the thymus well visualized (arrow). (b) Color Doppler ultrasound image showing absence of pulmonary vessels and absence of trachea below the pharynx (arrow).
Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.
LETTERS TO THE EDITOR
Letters to the Editor
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the lungs should be, which may make the correct identification of the condition more difficult3 . The most important differential diagnoses to exclude are congenital diaphragmatic hernia, cystic adenomatous malformation and pulmonary sequestration. R. Ramanah†, A. Martin†, V. Guigue†, F. Arbez-Gindre‡, J. Piard§, P. Terrosi¶, E. Alanio¶, R. Favre**, D. Gaillard†† and D. Riethmuller*† †Department of Obstetrics and Gynecology, Besanc¸on University Medical Center, Besanc¸on, France; ‡Department of Pathology, Besanc¸on University Medical Center, Besanc¸on, France; §Department of Genetics, Besanc¸on University Medical Center, Besanc¸on, France; ¶Department of Obstetrics and Gynecology, Reims University Medical Center, Reims, France; **Department of Fetal Medicine, Strasbourg University Medical Center, Strasbourg, France; ††Department of Genetics, INSERM U903, Reims University Medical Center, Reims, France *Correspondence. (e-mail:
[email protected]) DOI: 10.1002/uog.11146
References ¨ 1. Schmit H. Ein Fall von vollstandiger Agenesie beider Lungen. Arch Pathol Anat 1893; 134: 25–32. 2. Vettraino IM, Tawil A, Comstock CH. Bilateral pulmonary agenesis: prenatal sonographic appearance simulates diaphragmatic hernia. J Ultrasound Med 2003; 22: 723–726. 3. Lee KA, Cho JY, Lee SM, Jun JK, Kang J, Seo JW. Prenatal diagnosis of bilateral pulmonary agenesis: a case report. Korean J Radiol 2010; 11: 119–122. 4. Claireaux AE, Feirrera HP. Bilateral pulmonary agenesis. Arch Dis Chil 1958; 33: 364–366. 5. Gaillard D, Puchelle E. Differentiation and maturation of airway epithelial cells: role of extracellular matrix and growth factors. In Lung development, Gaultier C, Bourbon JR, Post M (eds) New York: Oxford University Press 1999; 46–76.
Fetal hypothalamic hamartoma with suprasellar arachnoid cyst We report two cases of hypothalamic hamartoma associated with suprasellar cysts that were diagnosed by fetal magnetic resonance imaging (MRI) in our institution. In the first case, a 34-year-old woman, gravida 3 para 1, presented in the first trimester of pregnancy. She had undergone termination of a previous pregnancy because of midline fetal abnormalities (cleft lip and palate and absent cavum septi pellucidi, with normal karyotype). Ultrasound examination at 20 weeks’ gestation showed a 6.4 × 5.2-mm cyst anterior to the cerebellum. Fetal MRI at 21 weeks’ gestation showed a central suprasellar arachnoid cyst anterior to the midbrain with a 4-mm thick
Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Figure 1 T2-weighted sagittal magnetic resonance image of a fetus at 21 weeks’ gestation showing a 9 × 7-mm unilocular arachnoid cyst anterior and above the midbrain with solid tissue anterior to it.
semicircular arch of tissue anterior to the cyst, suggestive of a hypothalamic hamartoma (Figure 1). Termination of pregnancy was carried out at 22 weeks’ gestation. Postmortem examination confirmed the presence of a 2 × 2 × 1-cm mass arising from the hypothalamus, extending down in front of the midbrain and enclosing a cystic space between the cerebral peduncles to which the tumor was adherent but not fused. The fetus had a normal karyotype with no features of Pallister–Hall syndrome on postmortem. We did not test for GLI3. In the second case, a 28-year-old woman at 35 weeks’ gestation was referred to our institution after an ultrasound examination detected a 3-cm solid lesion anterior to the brainstem at the circle of Willis, associated with a 1.5-cm cyst. Fetal MRI showed a central arachnoid cyst anterior to the midbrain and a 3.2 × 2.9 × 2.6-cm hypothalamic hamartoma situated anterior to the cyst (Figure 2). This patient was lost to follow-up. Antenatal arachnoid cysts are usually detected in the third trimester, with some detected in the second trimester and at least one reported on first-trimester transvaginal ultrasound1 . These cysts are commonly located in the supratentorium and can exert a mass effect, giving rise to complications such as ventriculomegaly. In a series of primary arachnoid cysts observed in children, only four out of 67 cases were located near the sella2 . Congenital arachnoid cysts have been reported in association with abnormalities in chromosomes 9, 14, 18 and the X chromosome, and have also been observed in Pallister–Hall syndrome3 , an autosomal dominant disorder that comprises hypothalamic hamartoma, pituitary dysfunction, central polydactyly and visceral malformations4 . Hypothalamic hamartomas associated with suprasellar cysts are rare and there has been only one other report
Ultrasound Obstet Gynecol 2012; 40: 724–729.
