Expanding the phenotype of alveolar capillary dysplasia (ACD).
OBJECTIVE
To define the phenotype of congenital alveolar capillary dysplasia (ACD) as a first step toward mapping the responsible gene(s).


METHODS
Analysis of pathology reports and microscopic slides of 23 subjects with ACD and sequence analysis of two candidate genes.


RESULTS
Our review of the pre- and postmortem records delineates both the natural history of this condition and the associated anomalies. Our collection of families corroborates the likely autosomal recessive nature of this condition in some families and provides additional data for genetic and prenatal counseling. Anomalies of many organ systems were detected either in the prenatal period or during the hospital course. However, some major anomalies were not detected until postmortem examination. Left-right asymmetry and gastrointestinal malrotation emerge as important, previously recognized but underappreciated phenotypic features of ACD. Finally, we used sequence analysis to exclude mutations in the coding region of two candidate genes, bone morphogenetic protein type II receptor (BMPR2) and endothelial monocyte-activating polypeptide II (EMAP II), as candidates for ACD.


CONCLUSIONS
Understanding the clinical spectrum of ACD and the cloning of an "ACD gene" both have implications for counseling, for prenatal testing, and for understanding the molecular pathophysiology of ACD and other organ malformations that are associated with this condition.
Sen
Partha
P
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Thakur
Nivedita
N
Stockton
David W
DW
Langston
Claire
C
Bejjani
Bassem A
BA
D000015:Abnormalities, Multiple / Q000235:genetics*; D052006:Bone Morphogenetic Protein Receptors, Type II; D002196:Capillaries / Q000002:abnormalities*; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D010375:Pedigree; D010547:Persistent Fetal Circulation Syndrome / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011650:Pulmonary Alveoli / Q000002:abnormalities*; D011667:Pulmonary Veins / Q000002:abnormalities*; D016601:RNA-Binding Proteins / Q000235:genetics; D017421:Sequence Analysis
D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II