Neural tube defects in four Shetland sheepdog puppies: clinical characterisation and computed tomography investigation

Abstract

Background Here, we report on the occurrence of neural tube defects (NTDs) in four related Shetland sheepdog puppies. NTDs present as a range of congenital malformations affecting the spine, skull and associated structures. Despite the severity of these malformations and their relatively high prevalence in humans, the aetiology is not well understood. It is even less well characterised in veterinary medicine. Case report Affected puppies were investigated using computed tomography (CT) and then necropsy. CT identified a range of brain and spine abnormalities in the affected animals, including caudal anencephaly, encephalocele, spina bifida and malformed vertebrae. Other observed abnormalities in these puppies, including cranioschisis, atresia ani and hydrocephalus, may be secondary to, or associated with, the primary NTDs identified. Conclusion This case report describes multiple related cases of NTDs in an Australian cohort of dogs. This study also highlights the potential of advanced imaging techniques in identifying congenital anomalies in stillborn and neonatal puppies. Further research is required to investigate the aetiology of NTDs in this group of affected Shetland sheepdogs.

Comparison of inherited neural tube defects in companion animals and livestock

“…In humans, anencephaly (MIM 206500) is considered the second most common NTD (Botto et al, 1999), and can be further classified morphologically as either holoanencephaly (holoacrania; involving foramen magnum and fronto‐parietal region) or meroanencephaly (meroacrania; a less severe form where the posterior skull and foramen magnum are unaffected) (Danzer, Rintoul, & Adzick, 2017; Seller, 1987). The advanced imaging (computed tomography) and postmortem detailed in the above Shetland sheepdogs report (Thomas et al, 2020) clearly indicate that these cases can be classified as holoanencephaly. Further classifying animal cases to fit the human morphology types might enhance the ability to use them as a comparative animal model.…”

“…Anencephaly has also been identified in two related Shetland sheepdog pups (Thomas et al, 2020). Alongside anencephaly of the caudal brain, the first stillborn pup also had cranioschisis and a suspected encephalocele (Figure 1a,b).…”

“…Anencephaly is rarely reported in the veterinary literature (Table 2, Supporting Information Table S1), though a small number of cases are reported in livestock (D. Y. Cho & Leipold, 1978; Dennis, 1975a; Dennis & Leipold, 1972; Hiraga & Abe, 1986) and dogs (Huisinga et al, 2009; Ortega‐Pacheco et al, 2020; Thomas et al, 2020).…”

“…Pedigree analysis was conducted for the Shetland sheepdog cases, including two other related animals with spina bifida occulta and hydrocephaly. This identified several common ancestors, including one found in both the maternal and paternal lines of the majority of affected animals (Thomas et al, 2020). This common ancestor may carry a genetic mutation relating to the malformations seen, or may simply have been a popular sire effect in this population.…”

“…The hind limbs are placed in an abnormally wide position, including a mal‐positioning of the right paw which is flipped‐over on its dorsal aspect. Source: Image (a) was published as fig. 1‐A (Thomas et al, 2020). Image (f) was published as fig.…”