Our knowledge on inherited diseases and traits in animals is rapidly increasing with more than 298 bovine and 118 ovine single locus diseases and traits reported in Online Mendelian Inheritance in Animals (OMIA, omia.org). However, inherited conditions in production animals are often not diagnosed to have a genetic aetiology or are underreported, particularly when clinical signs are not pathognomonic for a specific disease and when only a few animals are initially affected. Early identification of emerging inherited conditions is crucial to allow identification of possible causative variants, development of affordable and readily accessible DNA diagnostics and implementation of management strategies to reduce the risk of breeding further affected animals. The following briefly outlines the broad aspects of investigating suspected inherited neurologic conditions in ruminants.
Comprehensive history is essential in prioritising differential diagnoses and assessing the likelihood of an inherited condition. Some aspects of standard history information that can assist in investigating an inherited disease are listed. A slow increase in the proportion of affected animals in the flock/herd over multiple years can indicate a recessive condition. Presentation of disease in mostly male animals can indicate an X-linked mode of inheritance. It is a common misconception that inherited diseases are congenital (present around birth) but if animals start presenting at a specific age this could indicate an inherited disease with late onset. If a specific group of animals on the property is affected, it needs to be investigated how this group differs to others on the property. Are cases seasonal and are there any exacerbating factors, for example handling, stress and heat? For ruminants with neurologic signs, plant toxicities are often an important differential and assessing whether animals have had access to causative plants is essential; pasture walks can often be invaluable. There is significant overlap in histopathology between plant toxicities and some inherited conditions and ruling out certain plant toxicities can often not be done at the lab alone. Determine if there have been any changes corresponding with onset of signs, including change in nutrition, management procedures or new animals on the property. For individual animals, are clinical signs stable or is there improvement or deterioration of signs over time?
To further assess likelihood of a possible inherited disorder, specific information relating to the breeding program should be collected as inbreeding can increase the risk of recessive diseases. Have rams/bulls been sourced from the same stud over multiple years (and thus may be related to each other) or is this a closed flock/herd? Have rams/bulls been retained in the breeding program and could have been mated with their offspring? Do affected animals trace back to one or a small number of rams/bulls? DNA parentage verification can assist to identify pedigree. If available, detailed pedigree information should be collected to allow pedigree analysis to identify the mode of inheritance and identify founder animals or animals at risk.
A physical examination provides essential information for the investigation of neurological diseases. Body condition score and muscle mass (loss, increased muscle mass, asymmetry) can help assess for metabolic conditions and give a clue as to the chronicity. Determine if there is any pain on movement of head, neck, back, limbs and/or hoof lesions.
Commence a neurologic examination at a distance. Determine the animal's mentation, how they are interacting with the environment, if there is any evidence of vision loss and if they are eating and vocalising normally. Assess the gait; is there evidence of ataxia, paresis, proprioceptive deficits, hypermetria, circling, head tilt or tremors (at rest and/or with movement). Where possible, patella reflex and withdrawal reflex may be assessed in some animals, however we have found this reflex to be quiet variable in sheep. Cranial nerve examination, in addition to assessing for vocalising, eating and sight, may include checking tongue tone and movement, assessing normal facial sensation, palpebral reflex, menace response, pupil size and symmetry, and where possible pupillary light reflex. Photos and videos can be valuable and allow assessment of histopathology in context of clinical presentation.
Samples will vary depending on the specific disease investigation. If a genetic cause is considered likely, contact EMAI prior to sample collection. Specific samples may be indicated in some investigations and may require specialised media to be sent in advance. If the animal is presenting like a known condition, we have tests available for a range of infectious and inherited diseases. If it is a suspected inherited disease for which no DNA diagnostics are currently available , DNA +/- RNA samples from affected animals, as well as DNA samples from potential related animals, can be useful for parentage verification and future research that aims to identify likely causal variants.
Collect a range of blood samples from live animals (serum, EDTA, LH), or if the animal is already deceased, aqueous humour, to help assess for differential diagnoses. Pericardial/pleural fluid can be also be used in some circumstances (e.g. foetus) for serology of infectious causes.
If a post-mortem is performed, fresh tissue is essential for ancillary diagnostics, including vitamins and minerals, heavy metals and infectious causes (PCRs, cultures). Submitting a range of formalin fixed tissue is recommended and testing can be done in a stepwise manner if needed. There can be significant overlap in presentation of some neurologic and musculoskeletal disorders. When submitting skeletal muscle, we recommend submitting from several different anatomic locations and identify each muscle submitted. When submitting forelimb and hindlimb muscle, also consider submitting skeletal muscle from a site that will not have lesions secondary to recumbency, e.g. paravertebral muscle, diaphragm. Peripheral nerve from the forelimb and hindlimb is recommend, again individually identified to assess for differences or similarities in lesions. If there is concern over reduced vision, collect the eyes including as much optic nerve as possible. After collecting required fresh samples of brain, preserving most of the brain for formalin fixation and histopathology is useful as for various conditions, lesions can be very location specific within the brain and several sites within the brain often need to be evaluated. When submitting spinal cord, formalin fixation prior to submission is preferred when possible. Submit and individually identify cervical, thoracic and lumbar spinal cord segments. Where possible, check the vertebral canal for any possible causes of compression (e.g. Johne's vaccine associated granuloma) or instability. If this is not possible in the field, call the lab to discuss options.
If you would like further information, please do not hesitate to contact Elizabeth Macarthur Agricultural Institute.