CONGENITAL ABNORMALITIES AND INHERITED DISORDERS

INTRODUCTION

Congenital disorders are those conditions that are present at birth. They may or may not be inherited – indeed most congenital disorders are not inherited. Some of the congenital and hereditary disorders manifest only at a much later age and so may not be obvious (or even detectable at all) at birth.

In spite of the non-heritable nature of many of the disorders, it is important to remember that inherited disease takes many forms. Recessive genes are carried unnoticed while some disorders have a complex genetic origin in which environmental and genetic factors combine to produce clinical disease. Furthermore some inherited diseases or tendency towards disease may be manifested only at a much later age or may not be expressed at all in the absence of other factors (including environmental and managemental aspects).

The specific genetic defects for some of the conditions are now well defined and this provides an opportunity for confirmation of the condition and for mechanisms for the control/elimination of the disease. However, in most of the disorders the precise genetics are not known – a genetic origin and heritability are presumed because the condition is overrepresented in a specific breed. Many (probably all) diseases probably have a genetic origin; that is, the subject is generally liable to the disease but such cases are not usually viewed as inheritable. There are many examples of these including the equine sarcoid and the condition of Culicoides hypersensitivity (‘sweet itch/ Queensland itch’). In both these conditions (and the others that fall into the same category) there is no indication at birth or in the neonatal or juvenile stages that the condition will necessarily affect the horse. In most cases other factors also need to be present for the disease to be expressed.

Highly fatal genetic combinations that occur at conception or during gestation result in embryonic or fetal death. In the former case the mare may simply cycle again (assuming that the death occurs before 35–50 days) or may abort. If an abortion occurs the fetus should be examined for any obvious genetic defect that could have been responsible.

As the genome of the horse is explored and defined the genetic nature of more of these conditions will be clarified. Genetic therapies have not been used but may become feasible in the future.

Some congenital conditions have a genetic origin whereas others are due to insults, metabolic derangements and malpositioning. The cause will have a significant implication for the subsequent breeding of the mare but in many cases etiology cannot be ascertained with any confidence and a considered opinion should then be given on the likely implications. Some of the congenital diseases are sporadic events and some may be related to the maternal status. For example, foals may be born with considerable musculoskeletal problems and goiter when the dam receives excessive dietary iodine. A mare that is infected at any stage of the pregnancy has the possibility of infecting the foal. For the most part, the placental type results in considerable fetal protection but some infections such as equine herpesvirus can cross the placenta and cause considerable problems of abortion or delivery of a sick foal. Piroplasmosis (Theileria/Babesia) infections are also known to be able to cross the placenta and so this diagnosis should be considered in foals born with a very high fever, jaundice and anemia in endemic areas.

In all cases a full clinical examination carried out either as a routine or because the foal is compromised in some way and all aspects should be considered even when the foal appears normal. The maxim that ‘sick newborn foals always look their best at 12–24 hours postpartum’ should always be born in mind.

Table 5.1 lists conditions that are known or thought to be inherited in horses.

Table 5.1

Conditions known or thought to be inherited in horsesa

^aThere are many other disorders that may be inherited in specific lines of various breeds but the true heritability of these with respect to breed alone is complex.

Dentigerous cysts (Fig. 5.1A) are a relatively common disorder that occurs as a result of an abnormal dental tissue developing on or adjacent to the side of the calvarium. They do not always have dental remnants and may be entirely soft tissue cysts with a secretory lining.

Figure 5.1 (A) Dentigerous cyst (arrow); (B) X-ray of cyst showing tooth-like structure on calvarium (arrow).

Dental abnormalities are relatively common in horses and may involve any of the teeth. The range of problems includes absence of one or more teeth (either the deciduous or permanent incisors or cheek teeth), maleruption (Fig. 5.2A) or supernumerary teeth (either incisor or cheek teeth but usually permanent teeth only).

Figure 5.2 (A) Maleruption and abnormality of incisors; (B) radiograph of maleruption of cheek teeth.

Treatment

Surgical removal of dentigerous cysts is described and is usually totally successful.¹ The procedure is described in standard surgical texts but removal of a firmly attached large dental remnant from the calvarium can be problematical.

Removal of abnormally erupted or malformed permanent teeth (whether incisor or cheek teeth) is always difficult. There are usually gross anatomical complications that have arisen as a result of the problem and so standard approaches may be more difficult.

Prognosis

Good.

OVER/UNDERSHOT JAW (SUPERIOR/INFERIOR BRACHYGNATHISM)

Etiology

This involves either the upper or lower jaw (maxilla/ mandible respectively) in which the incisor teeth do not meet.² The limits of normality occur when there is any occlusion of the normal occlusal surface. The problem is usually accepted as being due to an overlong or shortened mandible. It is widely accepted as hereditary in some cases but can arise in hypothyroid foals.

Clinical signs

• Parrot mouth (Fig. 5.3) or hog/sow mouth.³

Figure 5.3 Parrot mouth foal. This may not be very obvious in mild cases.

• May not be obvious at birth and some improve with age.

• Examination of the mouth and the congruity of the jaws is a normal part of the assessment of neonatal foals.

Treatment

• Surgical correction is possible in theory but is ethically questionable in view of the suspicion that it is sometimes due to an autosomal recessive gene. However, in cases that are associated with hyperiodic hypothyroidism (goiter due to iodine excess), treatment could be contemplated.

• The surgery is not simple and depends of course on the extent of the problem.

Prognosis

Mildly affected foals may grow quite normally and lead useful lives. Where there is gross discrepancy the incisive malocclusion is only a part of the problem and affected horses will require regular dental examination and treatment to remove molar hooks.

CLEFT PALATE (Fig. 5.4)

Etiology

Incomplete fusion of palatal shelf can affect either the hard palate or soft palate, or both.³ Hard palate clefts are rarer in foals than in other large animals while soft palate clefts are probably commoner. Defects of the palatal closure include hypoplasia of the soft palate in particular. Some cases have bilateral hypoplasia while others are unilateral. Rare cases have a mucosal fold instead of a palatal shelf.

Figure 5.4 (A) Foal with milk down the nose; (B) cleft palate; (C) endoscope view of cleft soft palate.

Clinical signs

• Nasal regurgitation of milk (Fig. 5.4A).

• Inability to suck if hard palate defective (possible failed passive transfer and developing sepsis).

• Failure to thrive.

• Secondary inhalation pneumonia.

Note:

• Nasal regurgitation of milk is dramatic in extensive hard palate clefts but may be slight or absent in smaller clefts and in soft plate clefts.

• Some cases grow reasonably but develop nasal reflux of food at older ages (possibly up to 4 years for first time!).

Diagnosis

• Clinical signs of dysphagia.

• Endoscopy (consider retrograde via tracheostomy) (Fig. 5.4C).

• Barium swallow contrast radiography.

• Fluoroscopy.

Differential diagnosis

• Congenital pharyngeal/subepiglottic cysts.

• Pharyngeal paresis/paralysis.

• Persistent frenulum of the epiglottis.

• Guttural pouch empyema/tympany.

Treatment

Surgery provides the only hope but is extremely difficult.⁴ Earlier cases have a better prognosis with surgery. There is variation in the extent and feasibility of repair.⁵

The ethical dilemmas of performing this surgery are considerable. The surgical approach is described in advanced text books of equine surgery.

Prognosis

The prognosis is poor.

HYPOPLASIA OF THE PALATAL SHELF

Short soft palate, unilateral (Fig. 5.5A) or bilateral (Fig. 5.5B) hypoplasia of the palatal shelf is rare in all species with only three known reports of the condition in the horse.^6–8 Due to the complexity of the process of swallowing and the neuromuscular activity associated with it, abnormalities of the palate have serious consequences and the only option for these foals is euthanasia.

Figure 5.5 Hypoplasia: (A) unilateral; (B) bilateral. (1) = mucosal fold remnant of palatal shelf; (2) = lingual lymphoid tissue.

ESOPHAGEAL STRICTURE

Etiology

Abnormal esophageal function in foals is associated with either congenital or acquired (see p. 263) conditions.

The embryological development of the esophagus creates opportunities for the development of strictures or lack of patency. Congenital esophageal strictures are relatively common in foals compared with other species but in any case are rare.

Complete non-patency is not recorded but several types of esophageal strictures have been identified.⁹

A variety of breeds appear to be susceptible (e.g. Thoroughbred,¹⁰ Appaloosa¹¹ and pony¹²). Congenital narrowing of the esophagus involving the distal third has been reported in a number of Haflinger breed horses.

Congenital web strictures have been described. These are embryological remnants of the developing esophagus and usually occur in the upper third of the cervical esophagus. They are usually frail and break naturally with ingestion of solid food. Occasionally they do not break down naturally and cause a clinical problem.

Persistent aortic arch with accompanying esophageal compression has also been described in foals.

Clinical signs

• Congenital abnormalities of the esophagus manifest shortly after birth usually with nasal reflux of milk – large volume regurgitation of milk out of both nostrils shortly after nursing.

• Recurrent episodes of choke with nasal regurgitation of milk or sometimes saliva (or both).

• Older foals may have mixtures of feed material and milk coming from nostrils.

• In a few cases (e.g. esophageal web strictures) the signs may resolve spontaneously or with minimal interference.

Diagnosis

• Clinical signs and endoscopic examination of upper airway, pharynx, and esophagus will reveal narrowing with or without active inflammation. Endoscopy may reveal evidence of abnormal mucosal folds.

• Ultrasonographic examination may be helpful in determining the severity and density of the strictured tissue and so give an indication of whether it was a genuine congenital web stricture or an acquired stricture.

• Contrast radiography (Fig. 5.6), contrast fluoroscopy (during feeding or induced swallowing) or computed tomography may be of diagnostic assistance.

Figure 5.6 X-ray of esophageal stricture using an inflated cuffed tube as a contrast.

Differential diagnosis

• Acquired strictures resulting from esophageal trauma (see p. 267).

• Direct external trauma (with or without esophageal rupture).

• Cleft palate.

• Persistent frenulum of the epiglottis.

• Simple choke (feed or acute foreign body obstruction in esophagus) (see p. 269).

• Persistent aortic arch.

Congenital ectasia of the esophagus is a rare but important condition in foals. In some cases of dilatation the problem is secondary to either a neurological ‘spasmodic’ disorder of the distal (smooth muscle) portion or to external constricting bands created by persistent vascular rings (vascular ring anomalies ¹⁵).

Figure 5.7 (A) Esophageal dilation; (B) megaesophagus.

The condition is most often ectasia of the middle third of the esophagus (from the heart base to the mid neck).

Clinical signs

• Foals are apparently normal at birth but develop recurrent choke as soon as they start taking solid feeds.

• Postural regurgitation of milk may be observed.

• Episodes of choke are sometimes difficult to relieve and there may be secondary esophageal ulceration with exacerbation of the problem.

This is a recently recognized congenital abnormality that is commonest in heavy horse foals (e.g. Shire). The condition appears to centre on an obstruction or discontinuity of the lacteal system in the mesentery of the small intestine. Milk feeding results in lacteal engorgement and overflow into the peritoneal cavity (Fig. 5.8B).

Figure 5.8 (A) Lacteal obstruction; (B) peritoneal fluid. Note: Lacteal obstruction is a recently described condition that mainly affects heavy breeds and is characterized by mild but persistent colic. Removal of the affected lops of jejunum resulted in a cure. The peritoneal fluid was a distinctive milky white color.

There is no evidence to support or refute a hereditary aspect to the condition.

Clinical features

• Mild abdominal pain.

• Failure to thrive.

• Mild fluid abdominal distention.

• Reduced food intake and reduced appetite.

Diagnosis

• Mild abdominal pain.

• Ultrasonography shows accumulation of peritoneal fluid with a higher density than other fluids.

• Paracentesis shows a severely opaque milky white or slightly orange peritoneal fluid (see Fig. 5.8B). The slightly pink appearance is due to red cell leakage and lysis in the fatty fluid.

Differential diagnosis

• Other forms of mild colic (see p. 237).

• Other causes of failure to thrive (see p. 348).

• Peritonitis.

Treatment

Laparotomy is essential to establish whether the disorder affects a limited length of the jejunum. If more than 25% of the jejunum is affected the outlook is poor or hopeless but if the affected portion can be surgically resected then the foal may survive.

This is a neurological-based complete non-strangulating small intestinal obstruction. It is a genetic, inheritable (recessive) disorder involving a complete congenital absence of intrinsic myenteric plexus in terminal small intestine/ileum, cecum and entire colon, resulting in the characteristic ‘lethal white foal syndrome’. The most severely affected portion is the ileum and so affected foals develop ileus of the ileum but wider gut involvement is also possible. There is a complete absence of normal propulsive intestinal movement.

In addition, the presence of the mutation prevents normal neural mediated colonic development and enervation. Foals are born with narrowed or absent portions of the small colon.

The condition is virtually restricted to white foals from Overo–Paint breeding.¹⁷ This genetic defect is caused by the presence of the Ile118Lys EDNRB mutation, which is associated with a white foal usually from Overo–Overo breeding although the gene may be present in other color patterns. Some white foals do not have this mutation.

Genetic studies based on DNA diagnostic testing for the lethal white gene reveal that the lethal white overo has two copies of a gene that in a single copy usually produces the color pattern known as overo.

Clinical signs

• Foal is a pure white color at birth (Fig. 5.9A). A few cases have a limited faint brown/orange tinge to the ear tips and tail.

Figure 5.9 (A) Standing lethal white foal; (B) colicking.

• They stand and nurse normally and appear to be healthy for 1–4 hours after birth.

• Within 2–24 hours affected foals begin to show colic (Fig. 5.9B), and lethargy. Then the foal usually develops an intractable, untreatable and unremitting colic that does not respond to analgesics.

• Bloating with progressive abdominal distention develops.

• No fecal material is passed (or is present in the rectum).

Diagnosis

• A white foal with no passage of meconium or fecal material is almost pathognomonic although not every white foal has the disease.

• Non-responsive colic within a few hours of birth in a white foal of the Paint breed is pathognomonic but it is also important to consider other (possibly resolvable) causes of severe unremitting colic (see p. 237).

• Clinical, radiographic and ultrasonographic evaluation points to complete bowel obstruction. Some cases have an incomplete intestinal tract also (see p. 104).

Differential diagnosis

• Meconium obstruction.

• Atresia coli/atresia ani.

• Colonic torsion.

• Strangulating and non-strangulating obstructions.

• Severe clostridiosis/enteritis.

Breeders of paint horses are very aware of the condition. Genetic testing to detect the defect associated with this condition can be performed on hair samples (or any other body tissues).^* Hair samples for testing must be obtained by plucking (not clipping) and the results of the test will usually be known by 2–3 weeks after submission. Because the testing process takes a significant time, usually the importance of the diagnosis relates to the parents rather than the foal.