Overview of the Issue

Introduction

Congenital defects are abnormalities of structure, function or metabolism that are present at birth. A defect may cause physical impairment or it may cause the death of the kitten, before or after birth. Congenital defects in stillborn kittens often go unrecognized because few stillborns are submitted for complete necropsy. Many congenital defects are cosmetic or minor, while others may cause serious impairment of health. Not all congenital defects are heritable.

Congenital defects may be:

 Obvious at birth, e.g. cleft palate

 Found only with diagnostic testing or at necropsy, e.g. diaphragmatic hernia

 Subtle abnormalities found only with sophisticated testing, e.g. lysosomal storage diseases

Prevalence of Congenital Defects

It has been suggested that cats have fewer congenital defects than many other domestic animal species, such as the dog, cow or horse. Approximately 3-5% of all human infants are born with a congenital defect and many childhood deaths in North America (30% or more) are due to congenital malformations. Congenital defects are also a significant contributor to neonatal mortality in the cat.

There are a few studies of congenital defects in pedigreed cats in the literature. Cave et al noted that congenital disease was more common in pedigreed kittens than in the non-pedigreed kittens in their necropsy study of 274 kittens aged up to 16 weeks. But the difference was not statistically significant and no individual breed of cat was significantly predisposed to congenital diseases in their data.

In a survey of 3,468 pedigreed kittens by Scott et al (1978), 6.8% had malformations. Individual breeds ranged from no defects reported to 17% (Colorpoint Shorthair) and 19% (Manx) of kittens affected. Scott et al (1979) reported 4.2% of Burmese kittens from one cattery had congenital defects, as well as 12.7% of Persian kittens from four catteries. The types of abnormalities reported included heart defects, open fontanelles, gastroschisis, eye and eyelid defects and gastrointestinal tract defects.

The most recent survey of congenital defects in pedigreed cats is found in Sparkes et al. In that analysis of 14 breeds in the UK, 14.9% of the litters included one or more kittens with congenital defects, ranging from 6% of the Devon Rex litters to 31% of the Tonkinese litters.

Some statistics have been published for congenital defects in non-pedigreed cats in research colonies. Young noted 2.8% of 633 kittens had congenital defects in a study of a specific pathogen free (SPF) colony. These congenital defects included intestinal and urinary tract abnormalities, chest and hind leg deformities, umbilical hernia and other defects. Lawler and Monti found 10.7% of 477 kittens in a minimal disease colony had congenital defects. The most common defect was cleft palate and several kittens were noted to have multiple defects. Addie et al reported that less than 1% of 280 kittens from an SPF colony had congenital defects.

Fetal Development

Feline fetal development can be divided into three stages:

 Pre-implantation (days 0-12)

 Embryogenesis (days 12-24)

 Fetal growth (day 24 to term)

The "critical period" is the stage during which each developing organ or structure is most sensitive to disruption. For most organs and structures, the critical period occurs during embryogenesis, in the third and fourth weeks of gestation. At the end of embryogenesis, the fetus is about 1/2 inch long. Developmental errors that occur during the first two weeks of gestation are usually lethal. It is also important to note that a defect in the development of one organ system or structure can result in the abnormal development of other organs or structures.

A teratogen is anything that disrupts normal fetal development, e.g. a drug or chemical. The timing of exposure of the fetus and the dose are important factors in determining outcome. Embryos are susceptible to teratogens, but this susceptibility tends to decrease as the critical developmental period for each organ system passes. This makes the fetus increasingly resistant to the effects of teratogens with age, with the exception of structures that differentiate late in gestation, such as the cerebellum, palate and urogenital system.

Causes of Congenital Defects

Congenital defects may be heritable, and the inheritance pattern or gene(s) responsible may or may not be known. A few congenital defects are due to chromosomal abnormalities, such as pseudohermaphroditism.

Many congenital defects are not heritable, but caused by other factors, such as:

1.  Infections in utero

a.  Usually viral, e.g. panleukopenia virus as a cause of cerebellar hypoplasia

2.  Drugs

a.  e.g. griseofulvin as a cause of cleft palate

b.  Little is known about the effects of most drugs during pregnancy in the cat

c.  It is best to avoid drug therapy in pregnant queens unless benefits outweigh potential risks

3.  Chemicals, environmental toxins

4.  Hyperthermia

a.  e.g. fever, high ambient temperatures, resting on heating pads, radiators or hot air vents, etc.

5.  Poor intrauterine environment

a.  Inadequate development of the placenta

b.  Cystic endometrial hyperplasia/pyometra complex

6.  Nutritional factors

a.  e.g. taurine deficiency as a cause of musculoskeletal defects

In some cases, defects may be caused by interplay of both environmental and genetic factors.

What Breeders Can Do

When a kitten with a congenital defect is born, breeders naturally want to know what caused the defect and whether the defect is heritable. Investigation of congenital defects requires asking and answering important questions:

 Is there a breed or familial predisposition (suggesting a hereditary cause)?

 Are there multiple defects in one kitten or multiple defects in the litter (suggesting a non-hereditary cause)?

 What were the results of any previous matings of the parents with each other?

 What were the results of any previous matings of the parents with other partners?

 Are there any potential contributing factors in the management or diet of the queen?

 Was the queen ill during pregnancy?

 Was the queen given any drugs or vaccinations during pregnancy?

It is important for breeders to monitor the health of their breed by:

 Collecting health data, including kitten morbidity/mortality data, on a regular basis

 Keeping excellent cattery records, including information on every litter and every kitten

 Communicating openly with each other and working together in breed clubs/groups

 Acting co-operatively to work on new defects as they emerge to:

 Determine the prevalence of a new defect

 Investigate the clinical aspects of the defect

 Collate pedigrees

 Work with clinicians, specialists, and geneticists to characterize the defect and its possible inheritance and develop a screening test

An important part of investigating congenital defects is performing necropsies on affected cats or kittens that die or are euthanized. Too often, many affected kittens have died and were not submitted for necropsy by the time a problem becomes apparent. For informative necropsies, the entire body should be submitted to a qualified pathologist within 24 to 48 hours. The body should be refrigerated and not frozen if possible. If there is a long delay expected before the body can be examined, the veterinarian can take samples of all major organs (or collect entire organs) for fixation in formalin and freeze the rest of the body. It is also important to supply the pathologist with the complete medical history of any affected kittens.

Molecular genetics is the marriage of classic genetics and molecular biology techniques. New laboratory techniques allow researchers to search for markers for genetic traits and diseases, and even to identify defective genes themselves. While relatively few specific genes responsible for diseases and defects in cats have been identified to date, feline geneticists have made rapid progress in recent years. For example, genes responsible for polycystic kidney disease, hypertrophic cardiomyopathy, and spinal muscular atrophy have been identified, allowing for the development of commercially available genetic tests.

Breeders and veterinarians can assist in the search for genes causing congenital defects by identifying individuals with abnormalities and having the foresight to bank samples that can be analyzed later on. Early in the course of an investigation, hundreds or thousands of tests must be run, and large DNA samples are necessary. Examples of samples that can readily be used as abundant sources of DNA include frozen reproductive organs from spay and neuter surgeries and frozen whole blood samples (but not serum or plasma). Formalin-fixed tissues are very poor sources of DNA. Buccal (cheek) swabs are also good DNA sources, but provide smaller amounts of DNA and so are best used once a genetic test is available.

Kitten Health Projects

The Internet provides an opportunity to collect data from a large group of breeders anywhere in the world in a simple and straightforward manner using web-based submission forms. Several breed-specific, prospective studies are currently underway or in data analysis. It is very important to gather enough data to know what is normal within individual breeds so that breeders and veterinarians alike can recognize what is abnormal. Such studies also allow the scientific collection of information important to breeders, such as common congenital defects or diseases within each breed, in a confidential manner. Breeders have shown a great willingness to collect data and use it to improve breeds and breeding practices. Such great stores of information and knowledge as breeders possess should not be overlooked in our efforts to better the health of cats.

A summary of data collected on congenital defects in several breeds is presented in Table 1. Some congenital defects are found in many breeds, such as thoracic wall defects (flat chest, pectus excavatum), gastroschisis, umbilical hernia and cleft palate. Other defects seem to be associated with certain breeds, such as craniofacial defect (Burmese), ocular dermoids (Birmans), and eyelid coloboma (Ragdolls). Most of these defects do not have a known inheritance pattern, and no screening tests are available to detect carriers should they be due to recessive genes. Most of the defects have not yet received attention from researchers or geneticists.

For more information on these breed-specific health studies, see: http://catvet.homestead.com/BreedProjects.html

Table 1: Congenital Defects in Some Pedigreed Breeds

COL = eyelid coloboma
CP = cleft palate
DER = dermoids (nasal and ocular)
FCK = flat chest defect
GAS = gastroschisis
HD = craniofacial (head) defect
PE = pectus excavatum
SYN = syndactyly
UH = umbilical hernia
XIPH = everted xiphoid process

References

1.  Addie D, Toth S. Feline coronavirus is not a major cause of neonatal kitten mortality. Feline Pract 1993; 21:13-18.

2.  Cave T, Thompson H, Reid SWJ, et al. Kitten mortality in the United Kingdom: a retrospective analysis of 274 histopathological examinations (1986 to 2000). Vet Record 2002; 151:497-501.

3.  Lawler D, Monti K. Morbidity and mortality in neonatal kittens. Am J Vet Res 1984;45:1455-1459.

4.  Noden D. Normal development and congenital defects in the cat. In: Kirk R, ed. Current Veterinary Therapy IX Small Animal Practice. Philadelphia: WB Saunders Co, 1986;1248-1257.

5.  Scott F, Geissinger C, Peltz R. Kitten mortality survey. Feline Pract 1978;8:31-34.

6.  Scott F, Weiss R, Post JE, et al. Kitten mortality complex (neonatal FIP?). Feline Pract 1979;9:44-56.

7.  Sparkes AH, Rogers K, Henley EW, et al. A questionnaire-based study of gestation, parturition and neonatal mortality in pedigree breeding cats in the UK. J Feline Med Surg, in press.

8.  Young C. Preweaning mortality in specific pathogen free kittens. J Small Anim Pract 1973;14:391-397.

For Further Reading: Articles

1.  Coates J, Kline K. Congenital and inherited neurologic disorders in dogs and cats. In: Bonagura J, ed. Kirk's Current Veterinary Therapy XII Small Animal Practice. Philadelphia: WB Saunders Co, 1995;1111-1120.

2.  Greco D. Congenital and inherited renal disease of small animals. Vet Clin North Amer: Sm Anim Pract 2001;31:393-399.

3.  Hoskins J. Congenital defects of cats. Compend Contin Edu Pract Vet 1995;17:385-405.

4.  Narfstrom K. Hereditary and congenital ocular disease in the cat. J Fel Med Surg 1999;1:135-141.

5.  Stepien R, de Morais H. Feline congenital heart disease. In: Bonagura J, ed. Kirk's Current Veterinary Therapy XIII Small Animal Practice. Philadelphia: WB Saunders Co, 2000;738-741.

6.  Sturgess C, Waters L, Gruffydd-Jones TJ, et al. Investigation of the association between whole blood and tissue taurine levels and the development of thoracic deformities in neonatal Burmese kittens. Vet Record 1997;141:566-570.

For Further Reading: Reference Texts

1.  Gough A, Thomas A. Breed Predispositions to Disease in Dogs & Cats. Oxford: Blackwell Publishing, 2004

2.  Vella CM, Shelton LM, McGonagle JJ, Stanglein TW. Robinson's Genetics for Cat Breeders & Veterinarians. 4^th ed. Oxford: Butterworth Heinemann, 1999