Genetic dwarfism usually involves a bone disorder where the bones do not grow and develop normally. These are called skeletal dysplasias or chondrodystrophies. In humans, there are over 200 conditions causing stunted growth (possibly as many as 400 conditions) and over 100 known skeletal dysplasias; of which achondroplasia is the most commonly seen. Achondroplasia dwarfism is also found in cats. It is likely that other dysplasias also occur in cats, having subtly different dwarfing effects.

The most common (and easily recognisable) form is achondroplasia dwarfism which shortens the long bones of the limbs while leaving the trunk (body) unchanged. Achondroplasia dwarfism is characterised by abnormal body proportions. Achondroplasia dwarfism is the result of a dominant genetic trait affecting the hormones which control bone growth. Typically, the growth of the limbs is stunted, while the size of the trunk and mental capacity are normal.

The condition causes abnormally short and deformed limbs; this is most noticeable in short-legged dog breeds where the limbs are bowed or twisted. It also typically produces a large head with undershot (bulldog) jaw and crowded, misaligned teeth. Other cranial problems may occur due to the abnormal head shape. The limbs are frequently bowed which may result in poorly articulating joints. The vertebrae may also be affected. Although most affected cats are mentally normal, their abnormal body proportions may result in slow development in early kittenhood. The large head may result in kittens being delivered by caesarian section as they are unable to pass through the birth canal. Stuck kittens are likely to die and would likely cause the mother to die.

In the Munchkin; these short limbs are the distinguishing feature of the breed and the other deformities associated with achondroplasia are avoided (as far as possible) by careful selective breeding, avoiding breeding those individuals which have spine or chest deformities. Although achondroplasia is typically associated with a large or abnormal head, Munchkins do not seem to suffer this effect and therefore may have a different condition with similar physical effects rather than true achondroplasia. The Munchkin trait is more likely to be pseudochondroplasia or hypochondroplasia.

Current dwarf and miniature breeds are described as healthy for the most part. As with any full size cats, some individual miniature cats may exhibit health problems although these will not be representative of the breed as a whole.

I received a report in March 2002 of a supposed breed called the Asian Miniature Cat. The correspondent, a veterinary technician, believed this to be a discontinued breed due to health problems. The breed apparently suffered from mental retardation, bad teeth formation (possibly due to a misshapen head), fused vertebrae and joints and also chronic bladder stones. It was sweet natured, mentally dim and resembled a bear cub when walking. This sounds like one-off genetic dwarf since dwarfism produces a compact, short-bodied cat, often with a disproportionately large head and possibly other abnormalities. I am not aware of any formally developed Asian Miniature Cat breed and it may be the result of an individual breeding dwarf cats together with crippling results for the offspring. Achondroplasia is variable in its effects (alternatively there may be mimic conditions which are not currently distinguished from achondroplasia). The descriptions sounds typical of the more severe form of achondroplasia dwarfism. No reputable cat breeder would wish to produce kittens which such severe defects.

I have also received an isolated report of a miniature Persian which had giardia (intestinal parasite), Ringworm, Horner's sydrome (neurological disorder affecting cranial nerves and characterised by eye abnormalities; can be congenital, or caused by trauma or infection) and luxation of patellas (slipping kneecaps requiring corrective surgery). This is not necessarily representative of the breed since those same conditions also occur in full-size cats of different breeds and in random-bred cats.

Notes: Giardia is an intestinal parasite carried by up to 10% of cats with no symptoms; a recently infected cat or an infected cat which becomes stressed may show symptoms. Ringworm is also carried asymptomatically by many longhaired cats. Horner's Syndrome is due to lesions in areas of the brain and may be due to bacterial or viral infection or to head injury as well as to inherited causes; symptoms include drooping eyelid(s), exposed third eyelid and pupils of different sizes. Luxating patellas may also occur due to injury; if there is an inherited component to the condition there are a number of different genes involved which makes it unpredicatable. It is known to be hereditary in Devon Rexes. These allegations, and others have been found to originate from a single disgruntled individual who has posted (often anonymously) to a variety of forums and boards with an ever-varying list of "late manifesting" ailments against anindividual breeder's cats. They should not be regarded as representative of the breed.

Kittening and rearing kittens proved to be a problem in miniature Siamese. There was high kitten mortality and the mothers seemed unable to produce adequate milk for their offspring. Bonnie Arnold's miniature Persians were originally cause for concern (until the genetics were better understood) because a miniature mother might produce a full size kitten - a 3 lb mother with a 4 oz kitten (which might rapidly outgrow its mother) would not be an ideal situation. Because of the small size, spay surgery may have to be delayed even beyond the 6 months stage to ensure that the cats are robust enough for anaesthesia and surgery.

As far as vets are concerned, many dwarf cats have no health problems while others have problems ranging from mild to severe. Dwarfism in Munchkins and related breeds has been studied (see below), but other dwarf cats are less well understood. When dwarf cats are encountered, X-rays, body scans and blood tests can be used to look for skeletal effects, internal abnormalities and abnormal hormone levels respectively. DNA tests will look for known mutations, but some cats are small due to natural variation.

LOCALIZATION OF A FELINE AUTOSOMAL DOMINANT DWARFISM LOCUS: A NOVEL MODEL OF CHONDRODYSPLASIA.
LYONS LA, FOX DB, CHESNEY KL, BRITT LG, BUCKLEY RM, COATES JR, ET AL.
bioRxiv. 2019:687210.

There are two general categories of dwarfism: disproportionate and proportionate dwarfism. Disproportionate dwarfs have shortened limbs with a normal trunk. Proportionate dwarfs are uniformly small. Disproportionate dwarfs result from genetic disorders involving bone and or cartilage growth in the long bones. Most proportionate dwarfs are due to hormonal abnormalities affecting all bones equally. Feline disproportionate dwarfism had not been clinically characterized prior to this study. Breeds developed from disproportionate dwarf cats were termed Munchkins and Napoleons (or Minuets). These have shortened forelimbs and hind limbs, implying lack of growth in the humerus, radius and ulna (forelimbs) and the femur, tibia and fibula (hind limbs). The condition affects males and females equally. The feline phenotype lacks the prominent forehead and other maladies associated with human achondroplasia. An autosomal dominant mode of inheritance is indicated.

Genome analysis localized the feline dwarfism phenotype to a region on cat chromosome B1. The remainder of the paper looked at the inheritance mode for this trait and also ruled out a gene known to cause disproportionate dwarfism in humans and dogs (FGFR3 region). This means there was a different, unidentified, gene involved in the Munchkin and derived breeds.

The initial dataset comprised 95 cats, including 26 unrelated (or only distantly related) dwarf cats, 11 related non-dwarf cats, and cats from the closely related breeds (Scottish Fold, British Shorthair, Selkirk Rex). The Munchkin dwarfism phenotype is unique and distinct, with only mild variations. All dwarf offspring in a 6-generation pedigree had at least one dwarf parent. No matings produced all dwarf kittens, meaning the dwarf parent(s) are expected to be heterozygous. Long-legged offspring were also produced from short-legged x short-legged matings i.e. the gene was dominant and the parents were heterozygous.

SKELETAL MANIFESTATIONS OF HERITABLE DISPROPORTIONATE DWARFISM IN CATS AS DETERMINED BY RADIOGRAPHY AND MAGNETIC RESONANCE IMAGING
Lisa M. Anderson, Derek B. Fox, Kari L. Chesney, Joan R. Coates, Bryan T. Torres, Leslie A. Lyons
Veterinary and Comparative Orthopaedics and Traumatology, Vol 34, No 5, 2021, pages 327–337

This studied the radiographic alignment of fore and hindlimbs and evaluated possible spinal disc disease in cats with feline disproportionate dwarfism (FDD). This is the form of dwarfism that causes short-legged cat breeds, first recognised in the Munchkin breed. Six FDD cats were included in the study: 4 males and 2 females. Genetic studies suggest the Munchkin form of FDD is caused by an autosomal dominant gene, UDP-glucose 6-dehydrogenase (UGDH). FDD cats are phenotypically similar to dogs affected by disproportionate dwarfism caused by an autosomal recessive gene called growth factor 4 (FGF4). Although caused by different genes, the affected cats and dogs had disproportionately short legs, often with bowing of the forelimbs. In dogs, the condition is also associated with spinal conditions.

It studied the limbs 5 FDD cats (confirmed UGDH mutation) and compared these to a large number of normally proportioned cats with moderate conformation and mixed breed origins. In addition to x-ray images of the cats, it took MRI scans of 2 FDD cats (4 year old spay and 9 year old neutered male) to evaluate the spine. All cats studied were skeletally mature (i.e. had stopped growing) with no previous history of lameness, orthopaedic disease, neurological disease or trauma. All of the FDD cats showed some curvature in the upper and lower limb bones; generally at the ends of the long bones. The radius (in the lower forelimb) had more severe curvature; the humerus (upper forelimb bone) was not twisted, but the radius showed twisting. In the hindlimbs, the upper bone (femur) and lower hindlimb bone (tibia) both showed some curvature, but there was no twisting of the bones. Compared to dogs with shortened limbs, x-rays found no evidence of osteoarthritis in FDD cats, but noted the sample size was too small to be conclusive. None of the FDD cats showed spinal abnormalities. The study concluded that FDD caused significant abnormalities at the ends of the limb bones, but was inconclusive regarding spinal disc degeneration compared to normally proportioned cats.

The breeder of the FDD cats studied presented the shortest-legged and longest-legged FDD cats from the cattery. Cats with the UGDH mutation can have highly variable presentation. Genetic and environmental modifiers probably affect the degree of limb deformity. The small sample meant it was not possible to correlate the degree of short-leggedness with the severity of curvature/twisting or elbow joint alignment.

A NEW DOMESTIC CAT GENOME ASSEMBLY BASED ON LONG SEQUENCE READS EMPOWERS FELINE GENOMIC MEDICINE AND IDENTIFIES A NOVEL GENE FOR DWARFISM.
BUCKLEY RM, DAVIS BW, BRASHEAR WA, FARIAS FHG, KUROKI K, GRAVES T, ET AL.
PLOS Genetics, October 22, 2020

An improved cat genome reference model has been developed from PacBio long sequence reads. The previous reference model contained over 300,000 gaps. The whole genome sequences of 54 domestic cats were compared to the new reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Among the mutations noted in the domestic cats, there was a complex structural variant (a complex deletion coupled with a nearby duplication) found in three unrelated cats with dwarfism. It was found in a region on cat chromosome B1 already known to be linked to dwarfism. This SV interrupted the UDP-glucose 6-dehydrogenase (UGDH) gene involved in making glycosaminoglycans. UGDH has not yet been associated with dwarfism in other species, including humans.

Part of the paper discussed the development of the genome references and its use in showing the relatedness of different breeds, and randombred cats from different regions (Asian region vs Northern European region). It also looked at mutations that could be models for human disease as well as improved detection of feline illnesses (affected cats and carriers) related to mutations. The majority of the 208,135 SVs identified were common across gene-sequenced cats, suggesting they don't have a major impact on feline health.
Napoleon (Minuet) cats must be frequently outcrossed as their defining trait of dwarfism is likely homozygous lethal in utero - Lyons LA, Fox DB, Chesney KL, Britt LG, Buckley RM, Coates JR, et al. Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia. bioRxiv. 2019:687210.

In the UGDH study, 109 cats were genotyped: 41 normally proportioned cats and 68 dwarf cats. One cat – a non-standard (long-legged) Munchkin x Selkirk – appeared to carry the UGDH mutation. This may have been a sampling error. No cats were homozygous for the UGDH mutation. Out of 11 cats where both parents were heterozygous for the UGDH mutation, 7 were heterozygous and 4 were homozygous for non-mutation. This matches the ratio of genotypes for a recessive lethal allele (Note: it does NOT say the UGDH mutation is recessive, it says that the ratio for lethality is the same). The paper stated that homozygotes were lethal in embryos and that one correctly functioning copy of UGDH (“wild type”) was sufficient for healthy development.

The growth plates (at the end of the long bones) of UGDH dwarf kittens was disorganised compared to that of normal kittens (stillborn kittens were submitted by breeders). In normal growth plates there are distinct zones for new growth (at the bone tip) and as this grows, the region behind it calcifies into normal bone. In dwarfed cats these zones are not distinct. The researchers suggested the mutation either causes a gain of function for UGDH with activity specific to growth of long bones, or that feline UGDH plays a unique feline-specific role in bone growth, where loss of function of this gene causes feline dwarfism. This needed further study.

Many conditions have multiple names while some genetically different conditions have a similar appearance and may be mistaken for each other. Some disorders have a range of effects and are not primarily associated with dwarfism. This list is based mainly on human data and only a subset of these conditions have been identified in cats. There is the possibility that others do occur but are not identified because the affected kittens may be reabsorbed during pregnancy, be stillborn or die early (and the bodies may be eaten by the mother). Such conditions are generally only noted in pedigree and pure-bred cats and for two reasons: firstly inbreeding causes normally hidden recessive genes to be exhibited and secondly (and perhaps most important) breeders are far more likely to investigate abnormal kittens and to ask for an autopsy on kittens which die early.

Achondroplasia: This is the classical form of dwarfism and, in humans, the most common form. A number of other genetic mutations produce almost identical effects e.g. hypochondroplasia, pseudoachondroplasia. True achondroplasia results in an enlarged head; pseudoachondroplasia does not. Although the Munchkin's condition is termed achondroplasia, the head size is normal and it may ultimately prove to be a different mutation. The occurrence dwarf cats with cranial abnormalities also suggest that different genes are at work. Dwarfism is not common enough in cats for a distinction to be made between these conditions.

Acrodysplasia with exostoses (acrodysplasia type V, trichorhinophalangeal dysplasia type II, trichorhinophalangeal syndrome type II, Ttichorhinophalangeal syndrome with exostoses, Langer-Giedion syndrome, Giedion-Langer syndrome): Genetic condition characterised by distinctive facial and cranial features. In humans these include mild/moderate dwarfism, large protruding ears, a bulbous nose, sparse hair, mild microcephaly (small-headedness) and often with mental retardation.

Acromesomelia (acromesomelic dysplasia): Characterized by short arms, legs, and fingers, and a slightly enlarged head.

Bulldog Syndrome: Noted in Dexter Cattle and always lethal. Affected offspring have gross cranial deformities and other skeletal abnormalities. Individuals are either stillborn or die soon after birth.

Chondroectodermal dysplasia (Mesoectodermal dysplasia, Ellis-van Creveld syndrome): A short-limb dwarfism associated with polydactyly, abnormal development of nails and often with congenital heart defects. Probably recessive as it is prevalent in inbred populations.

Congenital adrenal hyperplasia: A wide-ranging endocrine condition with serious medical problems. Afflicted individuals may grow faster initially, but will become smaller adults.

DeMorsier's syndrome (septo optic dysplasia, optic-nerve hypoplasia): A dwarfing condition and pituitary-gland disorder that also affects vision and brain function.

Diastrophic dysplasia (DD): This was once thought to be a form of achondroplasia. It is a form of short-limbed dwarfism accompanied by serious orthopaedic problems. In humans it may be associated with cleft palate, clubfeet, deformed hands, cauliflower ears and respiratory problems in early life. Kittens with cleft palates are unable to suckle and generally die, so this condition is unlikely to be diagnosed in cats.

Flat-Chested Kitten Syndrome: This syndrome is typified by a flat chest or compressed chest which, in severe cases, causes breathing difficulties and displacement of internal organs, ultimately leading to poor growth and death. Mildly afflicted individuals recover fully.

Focal mucopolysaccharidosis (acromicric dysplasia, geleophysic dysplasia, geleophysic dwarfism): Characterised by short limbs, small hands and feet and (in humans) a genial facial appearance. Associated with heart/breathing problems, overall delayed development and ear infections. Two types of mucopolysaccharidosis are seen in cats - these are described later.

Hypochondrogenesis: Characterised by short body, short limbs, large head where the jaw may be small and the forehead enlarged (in humans the face appears oval or egg-shaped). Associated with cleft palate and severe respiratory distress due to the small rib cage. Most affected individuals die soon after birth; survivors are generally found to have spondyloepiphyseal dysplasia congenita which has a similar appearance. In kittens, cleft palate would prevent suckling and lead to death, so this condition is unlikely to be diagnosed.

Hypochondroplasia: Visually this looks like milder form of achondroplasia, but genetically it is different. The effects are less pronounced than achondroplasia and there are fewer associated health problems. In species where dwarfism is poorly documented, it may be misclassified as achondroplasia.

Hypothyroid: A lack of thyroid hormone results in poor growth and dwarfed cats which retain kitten-like features.

Jeune's syndrome (asphyxiating thoracic dystrophy): Potentially lethal form of dwarfism characterised by respiratory and kidney complications. In kittens this would probably prove lethal and therefore not be identified.

McCune-Albright syndrome: Precocious-puberty condition (affects mostly females) typified by bone, endocrine, and skin abnormalities. Varies from lethal, through severe to benign and almost entirely asymptomatic.

Metaphyseal chondrodysplasia, McKusick-type (cartilage-hair hypoplasia, CHH): A form of short-limb dwarfism associated with fine, sparse hair, impaired immunity and anaemia.

Metatropic dysplasia: Similar to, and often confused with, Kniest syndrome.

Metatropic dysplasia type II (Kniest syndrome, Kniest dysplasia): Similar to spondyloepiphyseal dysplasia congenita (SEDc) and spondyloepimetaphyseal dysplasia, Strudwick (SEMD).

Morquio-Brailsford syndrome (Morquio syndrome, MPS-IV, mucopolysaccharidosis): A mucopolysaccharidosis (MPS) disease, caused by the body's inability to produce certain enzymes. In cats, MPS-I and MPS-6 have been recorded, both causing facial deformities (short broad nose with depressed nasal bridge) and spinal deformities

Multiple epiphyseal dysplasia (MED): Not usually noticed at birth, but in juveniles it causes unexplained pain in the hips, knees, and/or ankles and mild dwarfism.

Neuroaxonal dystrophy: A lethal disorder which causes degeneration of main neurons in the brain and progressive incoordination; it also reduces the body size but the kittens do not survive into adulthood.

Osteodysplastic primordial dwarfism (primordial dwarfism): Causes extremely short stature and, in humans, bird-like facial features.

Osteogenesis imperfecta (OI): A brittle bone disease. In humans, there are four types of OI; Type III being a dwarfing condition and also associated with hearing loss.

Pituitary dwarfism (growth-hormone deficiency, hypopituitary dwarfism, hypopituitarism, pituitary dwarfism, panhypopituitarism): Body proportions are preserved resulting in a midget individual. Panhypopituitarism means absence of all pituitary hormones; in this case, sexual development does not occur, juvenile features are retained and life expectancy is reduced. Deficiency of only the growth hormone prevents growth, but the affected individual matures sexually as normal.

Precocious puberty: Early growth is often faster than normal, sexual development occurs early, after which growth slows so that the adult size may be small.

Progeria (Huntington-Gilford progeria syndrome (Huntington-Gilford syndrome): A rare genetic disease that causes ageing at several times the normal rate. One of its effects is profound short stature.

Pseudoachondroplasia: Mimics achondroplasia in some ways, but is a different condition entirely. A short-limb dwarfism, but in this case, the head size and facial features are unaffected. It is associated with osteoarthritis and other orthopaedic problems.

Rhizomelic chondrodysplasia punctata (RCP): A very severe form of dwarfism with profound delays in developmental and physical growth.

Russell-Silver syndrome (Silver-Russell syndrome, Russell syndrome, Silver syndrome): Affected individuals are of low birth-weight and may have a poor appetite. The condition causes small stature and (in humans) a small, triangular face, low-set ears and incurved fifth fingers. Low birth-weight kittens with poor appetite would be unlikely to survive so the condition might go unnoticed should it occur in cats.

Spondyloepimetaphyseal dysplasia, Strudwick (SEMD , SMD): This is genetically different from spondyloepiphyseal dysplasia congenita (below) but has indistinguishable characteristics.

Spondyloepiphyseal dysplasia congenita (SEDc, SED): This causes in moderate to severe small stature and is associated with clubfeet, a cleft palate, barrel-chest and other orthopaedic problems. It is considered one of the most common forms of dwarfism in humans. Cleft palate would prevent kittens from suckling.

Spondyloepiphyseal dysplasia tarda (SEDT, X-linked spondyloepiphyseal dysplasia tarda, X-SEDT): A sex-linked variant of SED carried on the X chromosome, which means it affects males (who only have one X chromosome) more often than it affects females. Females must inherit two copies of the gene in order to be affected. Mild dwarfism.

Spider Syndrome: Causes irregular calcification of cartilage so that legs become distorted at the knee/hock joints and the affected individual develops a splay-legged stance. In addition the spine is affected, causing hunchback and a long neck. Noted in some sheep breeds.

Thanatophoric dwarfism: A lethal form of dwarfism that results in death at birth or shortly thereafter..

Turner syndrome: The absence of all or part of one sex chromosome causes Turner syndrome, which affects only females (since an embryo having a Y chromosome but no X chromosome will not develop, but one with only a single X chromosome will develop into an apparent female). Individuals are physically female and are small in size, do not develop sexually (therefore infertile). It may be associated with mental dullness, skeletal abnormalities, heart, kidney and thyroid problems and thyroid dysfunction. If this condition does occur in cats, it might go unnoticed unless those associated effects draw attention to it or unless an otherwise normal female proves infertile.