Double-outlet right ventricle (DORV), NUMB-related

Gene: NUMB

Transmission: Autosomal dominant

Mutation: Substitution, NUMB gene, MYH1 gene; c.416 C>T, p.(T139M)

Medical systems: Cardiac

Breeds: Chianina

Age of onset of symptoms: From birth to 5 weeks.

Double outlet right ventricle (DORV) disease is a congenital cardiac anomaly characterized by the implantation of the two great arteries of the heart, the aorta and the pulmonary artery, in the right ventricle. The most common manifestations of this disease are tachycardia, tachypnea, jugular venous pulsation, cyanotic mucous membranes, a right apical systolic murmur, generalized weakness, failure to thrive, and signs of respiratory disease refractory to treatment of choice. Transthoracic ultrasound can confirm or refute the position of the great arteries in relation to the right ventricle. DORV has been reported sporadically in individuals of a number of cattle breeds Angus, Brangus, Chianina, Hereford and Holstein.  To date, molecular characterization of DORV has been performed for a single Chianina animal, where a mutation within the NUMB gene was identified.  The NUMB gene is known to be involved in cell fate and left-right developmental decisions, including cardiac development.  Due to the dominant and sporadic nature of DORV, it is not considered to be a breed problem.  However, it should be considered in the differential diagnosis in a calf that presents with respiratory and cardiac clinical signs.

References:

OMIA link: [2556-9913]

Jacinto JGP, Häfliger IM, Caivano D, Drögemüller C. (2022) A germline de novo variant in NUMB associated with a double-outlet right ventricle in Chianina cattle. Anim Genet 53:713-714.  [pubmed/35748177]

McManus A, Moloney T, Kelly P, et al. (2020) An unusual presentation of developmental anomalies of the cardiovascular system including tetralogy of fallot, double outlet right ventricle, patent foramen ovale and persistent right aortic arch in a Friesian calf. BMC Vet Res 16:224. [pubmed/23605568]

Contributed by: Alexandra Ronci and Léonie Ward, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)