Alveolar capillary dysplasia

About: Alveolar capillary dysplasia is a research topic. Over the lifetime, 219 publications have been published within this topic receiving 5569 citations. The topic is also known as: Alveolar capillary dysplasia with misalignment of pulmonary veins.

Prolonged survival in alveolar capillary dysplasia syndrome.

Abstract: Survival for up to 101 days is reported in an infant with congenital alveolar capillary dysplasia (ACD) with misalignment of pulmonary veins using inhaled nitric oxide thereby offering the prospect of survival until lung transplantation can be performed. The patient was a 3040 g Caucasian girl delivered at 39 weeks gestation. She developed cyanosis, tachypnoea, and hypoxaemia at 12 h of age. Echocardiography demonstrated atrial and ductal right-to-left shunt and suprasystemic right ventricular pressure. Following evaluation of the effect of different dosages of inhaled nitric oxide (iNO) during cardiac catheterisation, the therapeutic dose was chosen to be between 2–10 ppm, with a target O2 saturation of 95%. Right ventricular pressure decreased from 90–110 mmHg before to 60–65 mmHg after starting NO inhalation. Mean systolic arterial blood pressure was 55–75 mmHg. Breathing rate ranged from 30 to 50/min. A sibling had died 5 years earlier at the age of 17 days from a similar clinical presentation and ACD had been diagnosed at autopsy. At the age of 23 days, an open lung biopsy was performed. Pulmonary lobules were abnormally developed and showed thickened immature septa. Alveolar capillaries were frequently located in a central position deep inside the septa and were rarely in contact with the alveolar epithelium. Pulmonary veins could be found within the bronchovascular bundles adjacent to the pulmonary arteries instead of their normal intra-acinar course away from the arterial branches (‘‘misalignment’’). Pulmonary arteries showed thickened muscular walls reflecting persistent pulmonary hypertension. In addition, prematurely muscularised arterioles were found within the pulmonary acini, the typical findings of ACD combined with misalignment of pulmonary veins (MPV). Pathological changes in ACD/MPV resemble a normal fetal lung at the canalicular stage and can therefore also be seen as an arrest of pulmonary development at this stage [3]. Over a period of about 3 months the infant developed normally. The child underwent evaluation for possible lung transplantation. However, starting at the age of 13 weeks, the child developed sudden attacks of oxygen desaturation whilst breathing normally. The attacks were resistant to therapy. At the age of 101 days, the child did not recover from one of these attacks. An autopsy was not performed. The course of ACD/MPV in female siblings of one mother and two different fathers is different from the inheritance pattern in the literature and eliminates a possible recessive pedigree [5]. The first child died during the neonatal period (day 17), the second, reported here in detail, after 101 days of life, both of respiratory distress and permanent pulmonary hypertension (PPHN). When the second child showed similar symptoms after delivery, and after other causes for respiratory distress and PPHN had been ruled out, ACD/MPV was assumed, and subsequently proven. To date, ACD/MPV is a fatal disease [2,6]. Progress in lung transplantation in infants during the past years offers a therapeutic option for patients with ACD/MPV. As demonstrated by our report, prolonged survival using treatment with iNO could serve as a bridge to lung transplantation [1,4]. C. Licht (&) Æ A. Vierzig Æ B. Roth Department of Paediatrics, Children s Hospital, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany E-mail: christoph.licht@uni-koeln.de Tel.: +49-221-4784391 Fax: +49-221-4785835

Persistent pulmonary hypertension of newborn due to congenital capillary alveolar dysplasia.

Abstract: Congenital alveolar capillary dysplasia is a rare and fatal cause of pulmonary hypertension in neonates. We report on a term baby with severe pulmonary hypertension unresponsive to high-frequency ventilation and nitric oxide. A diagnosis of alveolar capillary dysplasia was established on autopsy. We review the literature regarding pathophysiology, clinical presentations, associated malformations, and treatment trials.

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.