Hereditary patent ductus arteriosus and its sequelae in the dog.

Further studies of hereditary patent ductus arteriosus (PDA) in the dog show the defect to have a graded phenotypic expression. A high proportion of offspring of test matings had a fully patent ductus arteriosus, while a smaller proportion had a blind diverticulum of the ductus arteriosus which communicated with the aorta. This is considered to be a forme fruste of PDA, representing incomplete closure. Approximately 50% of pups with fully patent ductus arteriosus developed signs of left heart failure, and about 15% developed severe pulmonary hypertension with right-to-left or bidirectional shunts. Genetic analysis indicated that hereditary PDA in the dog is not a simple mendelian trait. Rather, it resembles a quasi-continuous or threshold trait with a high degree of heritability. Results were analyzed using a polygenic model with two developmental thresholds. Liability to defective closure of the ductus arteriosus increased with the proportion of the genome received from dogs with PDA. Moreover, in pups which had PDA, the incidence of serious sequelae (left heart failure and severe pulmonary hypertension) increased in a parallel fashion, suggesting that an increased liability to PDA was accompanied by an increase in the severitv of the lesion. KEY WORDS ductus diverticulum threshold trait heritability quasi-continuous trait left heart failure pulmonary hypertension vascular shunt • Persistent patency of the ductus arteriosus after birth (PDA) is one of the most common cardiovascular anomalies found in man (1, 2) and the dog (3-5). A number of reports of the familial occurrence of PDA have implicated genetic factors in the cause of this defect in man (6-11) but the mode of transmission and pathogenetic mechanisms involved are poorly defined. Increased consanguinity in the parents of patients with PDA has suggested that single or multiple genes of a recessive nature may be involved (6), whereas the occasional transmission of PDA through several generations has led other authors to propose a dominant mode of inheritance (8, 11). A recent investigation showed the risk of PDA in offspring of patients with surgically corrected PDA to be about 20 times that in the general population, but the data were not consistent with any simple genetic interpretation (12). Epidemiologic studies of congenital heart disease in a veterinary clinic population have suggested that genetic factors are important in the etiology of PDA in certain breeds of dogs;