Overgrowth Syndrome

Abstract

Large offspring syndrome (LOS) is a fetal overgrowth condition in bovines most often observed in offspring conceived with the use of assisted reproductive technologies (ART). Phenotypes observed in LOS include, overgrowth, enlarged tongues, umbilical hernias, muscle and skeleton malformations, abnormal organ growth and placental development. Although LOS cases have only been reported to be associated with ART, fetal overgrowth can occur spontaneously in cattle (S-LOS). S-LOS refers to oversized calves that are born at normal gestation lengths. ART-induced LOS has been characterized as an epigenetic syndrome, more specifically, a loss-of-imprinting condition. We propose that S-LOS is also a loss-of-imprinting condition.

Keywords: Abnormal offspring syndrome; Assisted reproduction; Large offspring syndrome; Overgrowth; Spontaneous LOS.

Figure 1.. ART Produced LOS.

Large bull calf produced by in-vitro procedures by RMR while at the University of Florida. The picture was taken when the calf was 2 days of age. The calf weighed 98 kg at birth and died at one week of age as a result of complications relating overgrowth, which included inability to stand up to suckle.

Figure 2.. Spontaneous LOS.

Case 1 (top)– A post-term 86 Kg (normal birth at birth = 40 to 50 kg) Holstein bull calf was delivered by emergency C-section due to dystocia. The calf was macrosomic, had a marked omphalocoele and macroglossia (right picture). The calf was mentally inappropriate and was euthanized at 1 day of age. Immunohistochemistry of the anterior pituitary and hypothalamus could not demonstrate an aberration that could explain the macrosomia. Case 2 (middle) - A pre-term 63 Kg Brown Swiss heifer (normal weight at birth ~ 45 Kg) calf was delivered by planned C-section. The cow was referred for her large size approximately 2 weeks prior to being term. The calf was mentally appropriate at delivery and had an omphalocoelce and bilateral flexural deformities of the front metacarpo-phanalngeal joint. The ompahlocoele was corrected surgically (picture on the right) and the flexural deformities by splints and physical therapy. The calf was discharged in good health and is apparently still performing well. Case 3 (bottom) - One day old Holstein-Friesian calf showing typical signs associated with LOS including absolute macrosomia, omphalocele, and asymmetry of the pinna. The calf presented in respiratory distress and was later euthanized.