Morphological Variation of “Complex Vertebral Malformation” in Holstein Calves

Abstract

Abstract.A study was performed to investigate the morphological expression of the inherited syndrome ''complex vertebral malformation'' (CVM) in Holstein calves. A total of 107 late-term aborted, premature, or neonatal calves suspected of having CVM were necropsied and retrospectively analyzed for the causal mutation in the gene SLC35A3. Sixty-two calves were homozygous affected, 16 were heterozygous, and 29 were homozygous normal. Calves affected by CVM were growth retarded. Vertebral lesions identified by radiography were present in 61 cases, of which 58 also had costal malformation. Malformation of the head, primarily in the form of dysplasia or palatoschisis, was present in 15 cases. Bilateral symmetric flexion of the carpal and metacarpophalangeal joints was present in all cases, whereas posterior arthrogryposis was found in 54 cases. Interventricular septal defects occurred in 33 calves, often in combination with other cardiac malformations. A wide spectrum of additional malformations was found. Other congenital syndromes were in most cases distinguishable from CVM on a morphological basis. However, a calf with a prenatal infection with bovine virus diarrhea virus constituted a phenocopy. The study demonstrated that the morphological expression of CVM is wide, but certain aspects, i.e., growth retardation, vertebral malformation, and symmetric arthrogryposis, are almost constant findings. However, cases without vertebral defects and phenocopies constitute a diagnostic problem. A presumptive diagnosis of CVM can in most cases be based on necropsy findings combined with information on descent and paternal CVM genotype, whereas a definitive diagnosis requires genotyping.

Incidence of bovine leukocyte adhesion deficiency, complex vertebral malformation, and deficiency of uridine-5-monophosphate synthase carriers in Brazilian Girolando cattle

“…Complex vertebral malformation (CVM) is a lethal hereditary condition characterized by growth retardation, vertebral malformation, and bilateral symmetrical arthrogryposis, leading to the premature death of calves (Duncan Jr. et al, 2001;Agerholm et al, 2004;Kanae et al, 2005). CVM is caused by a point mutation (G to T) at nucleotide position 559 of the solute carrier family 35 member 3, UDP-N-acetylglucosamine transporter (SLC35A3) gene on BTA3 (Thomsen et al, 2006).…”

A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation

“…CVM is a recessively inherited disorder with onset during fetal development, leading to frequent abortion of fetuses or perinatal death, and vertebral anomalies (Agerholm et al , 2004Nielsen et al 2003). Disease symptoms have not been observed in obligate carriers of CVM.…”

“…Detailed clinical characterization of CVM demonstrated a composite phenotype with axial skeletal deformities such as hemivertebrae, misshaped vertebrae, ankylosis of mainly the cervico-thoracic vertebrae, scoliosis, and symmetric arthrogryposis of the lower limb joints, craniofacial dysmorphism, as well as cardiac anomalies (Agerholm et al , 2004Nielsen et al 2003) (Fig. 1A,B).…”

“…The diagnosis of CVM can be difficult to make because of significant clinical heterogeneity among affected calves and the occurrence of phenocopies. A presumptive diagnosis can usually be obtained at necropsy in combination with pedigree information; however, a definitive diagnosis requires DNA testing (Agerholm et al 2004). The vertebrate axial skeleton is derived from somites generated by segmentation of the paraxial mesoderm in an intricate process that requires participation of two signal-transduction pathways, Wnt and Notch (Pourquie 2003;Aulehla and Herrmann 2004).…”

Evaluation of SLC35A3 as a candidate gene for human vertebral malformations

“…Vertebral malformations include fusion of the last two cervical vertebrae and distortion of the first three thoracic vertebrae, resulting in scoliosis. Other malformations also noted to occur in association with CVM include cardiac anomalies, cleft palate, epibulbar dermoids, micrognathia, and ventrally displaced ears [Agerholm et al, 2004].…”