Congenital Anomalies and Genetic Disorders

With congenital (existing at birth) abnormalities genetic influences are often suspected, but difficult to substantiate. Effects of nutrition, toxins, infections (i.e. environment) can have profound effects on genetic expression. The following list is not intended to cover every case report or every treatment associated with congenital/genetic diseases. An attempt was made to include the most common.

I. Ophthalmology

1. Microphthalmia [1] (unilateral or bilateral small globes)

1. Eye may occasionally be functional, but more commonly are nonfunctional.
2. Sporadic - Believed non-heritable.

2. Ectropion - Eversion of eyelid - Correct surgically
3. Entropion

1. Infolded eyelid causes corneal and conjunctival irritation, tearing, conjunctivitis, corneal ulceration.
2. Treatment: vertical mattress sutures to temporarily evert the lid plus appropriate medical therapy of the eye.

4. Nasolacrimal Duct Obstruction [1]

1. Usually via atresia of the nasolacrimal meatus
2. Clinical signs: epiphora (clear to mucopurulent), no nasolacrimal meatus upon exam of nostril.
3. Treatment is normograde passage of 3.5 or 5 French catheter with incision over end to create patency. Suture catheter in place for 10 days and treat associated dacryocystitis

5. Corneal Dermoid [1]

1. Focal skin-like tissue that involves temporal limbus and adjacent cornea and conjunctiva.
2. Unilateral or bilateral.
3. Treatment - Nothing or superficial keratectomy.

6. Cataracts [1]

1. Most commonly reported ocular anomaly of foals.
2. May be unilateral or bilateral, focal or diffuse and most common cause of blindness in young horses. Most often present as only ocular defect, but it may be associated with persistent pupillary membranes, persistent hyaloid structures, or multiple ocular anomalies.
3. Treatment - Depends on severity (focal or diffuse) - surgical extraction of lens, phaecoemulsification or euthanasia

7. Persistent Pupillary Membrane

1. Pigmented strands that arise from iris stroma.
2. May traverse pupillary opening (iris to iris) or anterior chamber (iris to cornea).
3. Also may contact anterior lens capsule leading to anterior capsular and cortical cataracts.

8. Persistent Hyaloid Vasculation [1]

1. Remnant of vessel from optic disc to posterior lens. It may persist normally until approximately 3 weeks of age.
2. Remnants on posterior lens may be associated with posterior capsular and cortical cataracts.

9. Retinal Detachment

1. Usually bilateral and complete with dilated pupil and hyper-reflective tapetum. Pupils are non-responsive to light. Retina is folded and gray.
2. Have not been treated with success.

10. Congenital Corneal Vascularization [2] has been reported in a Thoroughbred foal.
    Bulbar and palpebral conjunctivae were inflamed with superficial corneal vascularization which resolved spontaneously within 7 days. It is believed to be related to alterations in amniotic fluid and eye irritation.
11. Others [1]

1. Microcornea, megalocornea
2. Lenticonus/lentiglobus - Defect in lens shape
3. Microphakia - Small lens
4. Luxated lens
5. Aniridia - Complete absence of iris. Autosomal dominant trait in Belgians with secondary cataracts.

12. Others [1]

1. Microcornea, megalocornea.
2. Lenticonus/lentiglobus - defect in lens shape.
3. Microphakia - Small lens.
4. Luxated lens.
5. Aniridia - Complete absence of iris. Autosomal dominant trait in Belgians with secondary cataracts.

II. Gastrointestinal

1. Cleft Palate [3]

1. Failure of the hard or soft palate to close along its midline prior to birth.
2. Diagnosis - Palpation or visualization during physical exam for clefts in hard palate or visualization via endoscopy for soft palate. Foal will expel milk through nostrils during and after nursing. Secondary aspiration pneumonia frequently develops.

1. Differentiate from temporary pharyngeal paresis; no lesion and improves after 1-7 days of tube feeding.

3. Treatment - Euthanasia or surgical correction of smaller clefts of the soft palate or hard palate, or some foals without significant aspiration pneumonia become riding horses.

2. Atresia ani and Atresia recti [3]

1. Diagnosis - Physical exam, unable to defecate.
2. Potential surgical correction.

3. Ileocolonic aganglionosis ("Lethal White Foal")[4]

1. Seen in overo - Overo Paint horse crosses.
2. Congenital absence of myenteric ganglia in terminal portion of ileum, cecum and entire colon.
3. Associated with colonic atresia, but there are actually contracted areas of small colon often with meconium impaction.
4. Diagnosis - White foal from overo spotted x overo spotted breeding - foals normal at birth but cannot defecate leading to colic and death.
5. Condition is fatal.
6. Genetics: Overo lethal white gene is an allele to the recessive overo spotting gene which is lethal in the homozygote [5].
7. For information on genetic testing go to: www.vgl.ucdavis.edu/services/coatcolorhorse.php

4. Atresia Coli [6]

1. Any breed.
2. Signs similar to meconium impactions; pain, straining, abdominal distension, lack of meconium.
3. Include a good physical exam and hematology to evaluate systemic component.
4. May have membranous atresia, cord atresia with gut remnant connecting blind ends or blind end with no connection [6].
5. Surgical correction is difficult.

5. Parrot Mouth (Prognathism) [3]

1. Malformation of the "bite" via maxilla overgrowth or a short mandible.
2. Genetically transmitted.
3. Diagnosis - Physical exam.
4. Many severe cases manage quite well.

6. Esophageal stricture [3]

1. Found in association with persistent right aortic arch.
2. Found in mid esophagus - Cause unknown - may be congenital or traumatic.

7. Esophageal stenosis [7]

1. Reported in Thoroughbred colt; onset at 3 days.
2. Milk discharge from both nostrils when head lowered after nursing.
3. Endoscope or contrast studies reveal narrowed area near base of heart.
4. Tube feeding for several weeks lead to recovery

8. Diaphragmatic Hernia

1. May be due to failure of fusion of embryonic development or rupture from birth trauma.
2. Signs may be colic - Especially after nursing.
3. Diagnosis auscultation, ultrasound and chest radiograph.
4. Surgical repair possible.

III. Cardiovascular Disease

See Congenital Cardiac Anomalies

IV. Urinary System

1. Rupture of Urinary Bladder (See Ruptured Bladder & Uroperitoneum).
2. Bilateral Ureter Defect (See Ruptured Bladder & Uroperitoneum).
3. Persistent Membrane Over Glans Penis

1. Foals cannot extend penis and consequently urinate within the sheath.
2. Most resolve spontaneously or require minor surgery to correct; wait for several weeks.

4. Posterior Urethral Valves

1. Uncommon but has been recognized in colt foals.
2. Characterized by stranguria, pollakuria, azotemia.
3. May be present as a ruptured bladder or as a hydronephrosis.
4. Failure or difficulty to perform urinary catheterization
5. Successful treatment has not been documented in the veterinary literature.

V. Musculoskeletal System

1. Rupture of Common Digital Extensor Tendon [8].

1. Usually present at birth or shortly after.
2. Characteristic swelling over dorsal lateral surface of carpus via tendon rupture within carpal synovial sheath.
3. Diagnosis - Clinical signs, palpation - can develop associated with flexor tendon contracture.
4. Treatment - Stall rest for 4-8 weeks with or without splints.

2. Angular Limb Deformities - Congenital or Acquired (See Limb Deformities - Introduction, Limb Deformities - Flexural Deformities (Sagittal Plane) and Angular and Rotational Deviations - General).
3. Wry Mouth or Campylognathy or Deviated Premaxilla [3]

1. If severe may not allow foal to nurse.
2. Less severe cases may improve somewhat with time if foal can nurse

4. Contracted Foal Syndrome [9]

1. Bilateral contraction of the joints of the fore or hind limbs, or both.
2. Usually involves 3rd metacarpal or 3rd metatarsal articulation of first phalanx.
3. Scoliosis or torticollis seen in conjunction.
4. Frequently associated with cranial asymmetry or curvature.

VI. Nervous System

1. Cerebellar abiotrophy (hypoplasia) [10]

1. Seen at birth to 6 months of age in Arabian foals.
2. Ataxia, intention tremors, dysmetria, and no menace response.
3. Familiar in the Arabian and Gotland pony breeds only.
4. Genetic test available: www.vgl.ucdavis.edu/services/CA

2. Hydrocephalus

1. May have domed head appearance.
2. Signs usually present at birth and may improve temporally with treatment.
3. May present with signs suggesting Neonatal Maladjustment Syndrome.
4. Uniformly fatal.

3. Congenital Myoclonus of Peruvian Pasos [11]

1. Foals cannot rise without assistance.
2. When assisted to standing, foals can move but have stilted, rabbit hopping type gait.
3. With auditory and tactile stimulation have myoclonic contractions.
4. Bright alert responsive and good suckle.
5. No treatment is successful. Valium and muscle relaxants help symptomatically.
6. May erode hip joint due to myoclonic contractions.
7. Have deficiency of glycine receptor in spinal cord for synaptic inhibition.

VII. Skin

1. Junctional Epidermiolysis Bullosa [12,13]

1. Moderate to severe blistering of the skin and sloughing of the hooves at birth.
2. Lesions often develop after mild trauma.
3. Ulcers on mucosal surfaces.
4. Biopsy - epidermis separating from dermis by subepidermal clefts [14].
5. A loss of cohesion of basal epithelial cells along lamina lucida of basement membrane.
6. Seen in Belgian foals, autosomal recessive heritable condition (laminin 5 formation defect).
7. Genetic testing is available: https://vgl.ucdavis.edu/test/jeb-belgian

2. Hereditary equine regional dermal asthenia (HERDA) [15]

1. Predominantly in American Quarter horse lines.
2. Hyperextensible skin, scarring, and severe lesions along the back of affected horses.
3. Affected foals rarely show symptoms at birth. The condition typically occurs by the age of two, most notably when the horse is first being broken to saddle.
4. Treatment is not available, and the majority of diagnosed horses are euthanized because they are unable to be ridden and are inappropriate for future breeding.
5. HERDA has an autosomal recessive mode of inheritance and affects stallions and mares in equal proportions. Research carried out in Dr. Danika Bannasch's laboratory at the University of California, Davis, has identified the gene and mutation associated with HERDA.
6. For genetic testing go to: https://vgl.ucdavis.edu/test/herda

VIII. Muscular System

1. Glycogen branching enzyme deficiency [16-19]
   This is a recently recognized disease mainly of quarter horses

1. Clinical Signs

1. Abortion or still birth of foals.
2. Sudden death on pasture from the heart stopping or from seizures (associated with hypoglycemia).
3. Weakness, low body temperature at birth.
4. High respiratory rate leading to fatigue.
5. Contracted tendons in all four legs.
6. Weakness and inability to rise.

2. Diagnosis

1. Compatible hematology and chemistry; low WBC count, elevated CK, AST and liver GGT.
2. Hypoglycemia even with normal feeding.
3. A muscle biopsy can be performed to screen for muscle diseases at the University of Minnesota. To determine if the foal has GBED hair samples can be submitted to the Veterinary Genetics Laboratory at the University of California, Davis to test for the GBED genetic mutation. Submission forms and information are available on their website: https://vgl.ucdavis.edu/test/gbed
4. Dr. Valberg’s website has more information: https://cvm.msu.edu/research/faculty-research/comparative-medical-genetics/valberg-laboratory/for-veterinarians/obtaining-and-submitting-a-biopsy
5. Genetic testing - University of California, Davis, Veterinary Genetics Laboratory performs GBED testing. https://vgl.ucdavis.edu/test/gbed

3. Treatment
   All foals with GBED have died. No treatment is effective.
4. Hyperkalaemic periodic paralysis [20]

1. Etiology

1. Quarter horses and Quarter horse crosses
2. Autosomal dominant
3. Defect in the voltage dependent skeletal muscle Na+ channel alpha subunit

2. Clinical signs

1. Sweating, muscle fasciculations, 3rd eyelid prolapse.
2. Severe muscle cramping.
3. Episodes last 15-60 minutes.
4. Respiratory distress (paralysis of upper respiratory muscles).
5. Homozygous: respiratory stridor and upper respiratory tract obstruction.

3. Diagnosis

1. Hyperkalemia (6-9 mEq/l) or normokalemia during mild episodes.
2. Hyponatremia
3. Hemoconcentration
4. Mane or hair tail with the follicle for DNA testing, for more information go to: https://vgl.ucdavis.edu/test/hypp

4. Treatment

1. Mild episodes - Mild exercise, grain or corn syrup.
2. Severe episodes- Calcium gluconate, IV dextrose, insulin.

5. Prevention

1. Decrease dietary potassium intake; feed timothy hay or Bermuda grass and grain.
2. Do not feed alfalfa or supplemental oils!
3. Multiple feedings.
4. Regular exercise and turn-out.
5. Acetazolamide(2-4 mg/kg) or hydrochlorthiazide (0.5-1 mg/kg).

5. Polysaccharide storage myopathy (EPSM, PSSM, EPSSM) [21-24]

1. Etiology

1. Equine polysaccharide storage myopathy Type I and Type II are characterized by a defect in glycogen storage in skeletal muscle.
2. This disease is seen in many different breeds including Quarter horses, draft horses, Warmbloods and crosses of these breeds.
3. Skeletal muscles in affected horses have higher amounts of stored glycogen than in normal horses.
4. Affected horses also have higher levels of a complex polysaccharide which is resistant to amylase digestion, aiding identification of the disease by histopathology
5. Clinical signs – Not reported in foals- see references for adult information

6. Myotonia congenita

1. Quarter horses and Quarter horse crosses.
2. Periods of involuntary muscle contractions following stimulation or activity.
3. Animals show signs usually <1 year of age.
4. Well-developed musculature, pelvic limb stiffness or lameness.
5. Only skeletal muscles are affected, no progression seen beyond 1 year.
6. Myotonic dystrophy is a separate condition and it progresses to severe muscle atrophy and involves other organs.

7. Malignant hyperthermia [24-27]

1. Has been recognized in Quarter horses and Thoroughbreds.
2. The condition is inherited, autosomal dominant.
3. A defect of the ryanodine receptor leads to the condition and causes increased intracellular calcium accumulation.
4. The process of reabsorbing this excess Ca2+ consumes large amounts of ATP, and generates hyperthermia.
5. The muscle cell is damaged by the depletion of ATP and possibly the high temperatures, and cellular constituents "leak" into the circulation.
6. The process is triggered by certain drugs used for general anesthesia (inhalational anesthetics: halothane, isoflurane).
7. Treatment is available. Dantrolene can be given 4-5 mg/kg iv although it is very expensive.

IX. Other

1. Inguinal (scrotal) hernias

1. Usually seen within first few days of life. Manage by reduction into abdomen on a daily basis can often result in correction.
2. If extensive, treatment is surgery with removal of testicle on side of hernia.

2. Cryptorchidism [2]

1. Unilateral or bilateral - believed genetic.

3. Umbilical hernia (See Umbilical Problems & Hernia)
4. Severe Combined Immunodeficiency (SCID See Immunodeficiencies) [28,29].

1. Lethal genetic disease inherited as an autosomal recessive trait; identified only in Arabians.
2. Lack of functional B and T lymphocytes.
3. Death usually is due to infectious causes.

5. Agenesis of a lung lobe
6. Autosomal trisomy [30]

1. Standardbreds.
2. Developmental defects - Facial asymmetry (one eye higher than other), dorsomedial strabismus, dysmetric gait, small testes, poor condition.

7. Lavender Foal Syndrome

1. Seen in Egyptian and ½ Egyptian Arabians.
2. Foals are born of normal gestation length and cannot rise from lateral recumbency, struggle severely to rise, are bright and alert mentally but cannot stand and walk. If propped up, foal will temporarily assume abnormal position and collapse and resume struggling.
3. Physical exam normal - bright, alert, responsive.
4. Foals are born a lavender color or best described as a diluted color appearance.
5. Have not improved with nursing care for 1 week.
6. CNS lesions consisting of vacuolization in some neurons at post mortem.