Congenital Splay Leg Syndrome in Piglets—Current Knowledge and a New Approach to Etiology

Abstract

The porcine congenital splay leg syndrome (PCS), even though being of transient nature, is still one of the most important causes for piglet losses due to its high incidence and mortality. Although, described decades ago, the pathogenetic mechanism is still elusive. Numerous, mostly descriptive studies characterized the syndrome at clinical, histological and cellular levels but resulted in a highly diverse picture of the syndrome. Broad variability in phenotypical expression and, in case of proper care, the rapid recovery of affected animals complicated a systematical analysis of the underlying pathogenesis. Although, several environmental factors were discussed as potential causes of PCS, most of the evidence points to a hereditary basis of PCS. Nevertheless, only few of the suggested candidate genes from transcriptome and mapping analyses, like F-box protein 32 (FBXO32), could be confirmed so far. Only recently, a genome wide association study revealed genomic regions on five porcine chromosomes and named a number of potential candidate genes, among them homer scaffold protein 1 (HOMER1). This new candidate—a cellular scaffold protein—plays a role in a plethora of cellular signaling cascades, and is not only involved in skeletal muscle differentiation but also critical for muscular function. In this review, we critically elucidate the current state of knowledge in the field and evaluate current achievements in the identification of the pathogenetic mechanism for the syndrome.

Candidate genes for congenital malformations in pigs

“…The splay legs syndrome (also known as spraddle leg syndrome) is the most frequent lame disorder in newborn piglets and the most observed inherited malformations in pigs. The syndrome has high economic and welfare consequences on the swine industry (Schumacher et al, 2021). The affected piglets are not able to stand or walk due to temporary impairment of the pelvic muscle function that occurs early after birth (Papatsiros, 2012;Hao et al, 2017).…”

“…The affected piglets are not able to stand or walk due to temporary impairment of the pelvic muscle function that occurs early after birth (Papatsiros, 2012;Hao et al, 2017). Histologically, the syndrome is expressed as myofibrillar hypoplasia and characterised by a higher proportion of less developed and smaller myofibrils (Schumacher et al, 2021). Clinically, the syndrome appears in various forms, from ataxia (sitting like a dog with a possibility to stand up) through the uncoordinated movement of rear legs (piglet is not able to get up without help) or the splaying of rear legs (movement is done just with the front legs) to a severe form, in which both the front and rear legs are splayed (piglet is not able to move).…”

“…An overview of the candidate genes associated with the syndrome is presented in Table 1. The primary pathological mechanism of the syndrome includes atrophy of muscle fibres and delayed skeletal muscle maturation at birth (Schumacher et al, 2021). Therefore, three promising candidate genes, NREP, FBXO32, and HOMER1, associated with myogenic differentiation, atrophy, and muscle development should be considered for the study of myofibrillar hypoplasia in pigs.…”

“…The identification of structural and functional proteins, genes, and quantitative trait loci allowed the study of congenital malformations (i.e. splay legs syndrome, hernias, and cryptorchidism) and other health traits at the genome level (Schumacher et al, 2021). Therefore, the identification and evaluation of genomic regions that control congenital defects was a breakthrough for the breeding programs (Sevillano et al, 2015).…”

Congenital tremor and splay leg in piglets – insights into the virome, local cytokine response, and histology

“…Splay leg, spraddle leg syndrome, or porcine splay leg syndrome (PCS) is characterized by an impaired adduction of the hind limbs, and sometimes also the front legs [13]. The at-farm prevalence of splay leg ranges from 1-8% globally [14,15], with a lethality up to 50% due to hypoglycaemia or mother overlying, crushing [16]. The impairment of the limbs is attributed to a hypomyelination of the spinal cord and the nerves innervating the affected muscles and a myofibrillar deficiency described as myofibrillar hypoplasia, an impaired muscular differentiation [13,17,18].…”