16 q 24 . 1 microdeletion in a premature newborn : usefulness of array-based comparative genomic hybridation ( array CGH ) in persistent pulmonary hypertension of the newborn

Objective—Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-CGH in persistent pulmonary hypertension of the newborn (PPHN) and multiple congenital malformations. Design—Descriptive case report Setting—Genetic department and neonatal intensive care unit of a tertiary care children’s hospital Patient—We report the case of a preterm male infant, born at 26 weeks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 weeks of gestation. Karyotype analysis was normal and a 22q11.2 microdeletion was excluded by FISH analysis. A Caesarean section was performed due to fetal distress. The patient developed persistent pulmonary Flore Zufferey, Flore.Zufferey@chuv.ch Danielle Martinet, Danielle.martinet@chuv.ch Maria-Chiara Osterheld, Maria-Chiara.Osterheld@chuv.ch Florence Niel-Bütschi, Florence.Niel@chuv.ch Eric Giannoni, Eric.Giannoni@chuv.ch Besuchet Schmutz Nathalie, Nathalie.Besuchet@chuv.ch Jacques S Beckmann, Jacques.Beckmann@chuv.ch Xia Zhilian, css@sanger.ac.uk Pawel Stankiewicz, pawels@bcm.tmc.edu Claire Langston, CXLANGST@texaschildrens.org Florence Fellmann, Florence.Fellmann@chuv.ch Consent Written informed consent was obtained from the parents for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interest The authors declare that they have no competing interests. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Pediatr Crit Care Med. Author manuscript; available in PMC 2013 May 16. Published in final edited form as: Pediatr Crit Care Med. 2011 November ; 12(6): e427–e432. doi:10.1097/PCC.0b013e3182192c96. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hours of life. An autopsy revealed partial atrio-ventricular canal malformation and showed bilateral dilatation of the renal pelvocaliceal system with bilateral ureteral stenosis, and annular pancreas. Array-CGH analysis (Agilent oligoNT 44K) showed an interstitial microdeletion encompassing the FOX gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Some features were less prominent due to the gestational age. Conclusions—Our review of the literature shows that ACD/MPV is rare, but probably underreported. Prematurity is not a usual presentation and histological features are difficult to interpret. In our case, array-CGH revealed a 16q24.1 deletion leading to the final diagnosis of ACD/MPV. It emphasises the usefulness of array-CGH analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory PPHN and multiple congenital malformations.