Chondroplasia-like Dwarfism

ACAN-Dwarfism

Genetic testing possible - see at genetic testing!

Liz C./Threnody works
Liz C./Threnody works

Caused on the ACAN locus by 4 known mutations (more mutations likely exist but have not been isolated yet). All 4 mutations can combine and express together as compound heterozygotes in various pair combinations (D1/D2 ect.)
Certain mutations, and combinations of these mutations, are lethal and result in aborted foals. Half of all combinations are lethal, the other half are viable.


Physical Affects

There are multiple physical affects from this form of dwarfism:

  • Cartilage and bone growth are inhibited causing compacted bodies limbs and craniofacial (head/face) deformities.
  • Legs can be deformed with ligament, bone, and joint malformations. They often require special shoes, leg braces, or even surgery.
  • Underbites and tooth crowding can occur due to inhibited jaw and facial growth.
  • Premature arthritis is common- Overall compacted appearance.
  • Roach backs and muscle atrophy are common.
  • The ribcage is compacted and the organs often continue to grow as normal, restricting inside the body cavity.
  • Roached backs and bloated body cavities become more pronounced with age.


Not all ACAN dwarves will express in the same manner or to the same extent due to various gene combination possibilities.

Affected Breeds: American Miniature Horse, Shetland Pony, Welsh, and their crosses


(English text by Liz C./Threnody works, this is a link)


Genotype/Phenotype descriptions

General descriptions of the five alleles of ACAN including novel combinations and resulting phenotype

 

Genotype Phenotype
 N/- normal, no dwarfism
D1/D1 ... were early gestational lethal dwarf
D1/D2 ... were early gestational lethal dwarf
D1/D3 ... were early gestational lethal dwarf
D1/D4 ... were early gestational lethal dwarf
D2/D2 ... were dwarf
D2/D3 ... were dwarf
D2/D4 ... were dwarf
D3/D3 no samples of this genotype, possible due to sampling size
D3/D4 ... were dwarf
D4/D4

no samples of this genotype, possible early gestational lethal dwarf

 

(Source: John E. Eberth, “Chondrodysplasia-Like Dwarfism in the Miniature Horse”, University of Kentucky)

 

 


ACAN D1 Genotypes (fetal lethal)

(= single base deletion in NCBI exon 2)

 

Genotypes involving D1 in combination with any other mutant allele appeared to be fetal lethals. D1/D1 is characterized as showing fetal abortion.

 

·  growth is extremely small stature, disproportionate dwarfism with a cranium large und domed for gestational age,

·        extremely low nasal bridge

·        exteme micrognathia with severely retruded muzzle,

·        cleft palate and protruding tongue,

·        ears set low and to the rear of cranium and large bulging eyes,

·        neck appears to be almost non-existent even in early gestation,

·        trunk involves a large abdominal hernia and extremely short vertebral column with ribs extremely short and thin,

·        limbs show severe micromelia and appear to involve changes in limb bones that are consistent with failure of endochondral ossification,

·        all bones are poorly ossified for gestational stage.

 

When novel combinations of D1 allele occur with other ACAN dwarf alleles, the resulting fetus is also lethal.

 

(Source: John E. Eberth, “Chondrodysplasia-Like Dwarfism in the Miniature Horse”, University of Kentucky)

 


ACAN D2 Genotypes

(= single SNP substitution in NCBI exon 6)

Horses inheriting the D2 allele and D2, D3, D4 were viable.

 

·         disproportionate short stature with short barrel

·         craniofacial has a disproportionately large head with pronounced frontal bone domed prominence,

·         enlarged eyes and orbit with a low and severly shortend nasal bone

·         retruded muzzle and under bite of varying severity,

·         airway obstruction develops and it is possible to be “central” in origin (due to foramen magnum compression) or “obstructive” in origin (due to narrowed nasal passages), necropsies were inconclusive. Symptoms of airway obstruction include snoring and laboured breathing.

·         limbs are short and thick comparatively to similar aged normal foal with various ranges of leg bowing due to joints,

·         joints are enlarged at birth with limited joint mobility and flexation,

·         flexion contractures of hips, small pelvis size for overall size with rotation (goose rump),

·         a pronounced shortened neck is noticeable at birth,

·         the development of slight roach back and variable stiffness occurs with age,

·         the barrel appears shortened due to slight curvature of spine,

·         motor milestones are often delayed secondary to joint deformities,

·         joint contractures and roach back progress with age,

·         progressive and painful joint enlargement can be accompanied by flexion contractures in all limb joints causing abnormal hoof growth very early,

·         muscle atrophy results from disuse

 

Novel combinations of D2 allele with other ACAN dwarf alleles express both mutation´s characteristics.

 

(Source: John E. Eberth, “Chondrodysplasia-Like Dwarfism in the Miniature Horse”, University of Kentucky)

 

 

On the pics are shown dwarfs of the following types: D2/D2, D2/D3, D2/D4


ACAN D3 Genotypes

(=single base deletion in NCBI exon 11)

Offspring with D3 plus D2, D3 and D4 alleles were viable. The samples collected did not demonstrate any homozygous Miniature dwarf genotype D3/D3. It is considered to be a rare mutation. The homozygote D3 at this time is not considered a lethal due to novel combinations being viable, however, it is lethal with D1.

 

·        disproportionate short stature with mature characteristics less severe than genotype D2/D2,

·        craniofacial structures are disproportionately large head with relative frontal bone slight domed prominence,

·        enlarged eyes and orbit with a low and relatively shortened nasal bone,

·        some show a retruded muzzle and generally have an under bite but not always,

·        limbs show rhizomelics shortening usually with bowed forelegs with enlarged joints and thick long bones at birth,

·        limited joint flexion predominantly affecting the knee, stifle, pattern and hock joints initially,

·        progressive joint contractures of the pastern cause abnormal hoof growth with age,

·        the development of a progressive roach back and hip rotation occur with a relatively shortened neck,

·        airway obstruction develops early and progresses with age,

·        muscle atrophy results from disuse

 

Novel combinations of D3 allele with other ACAN dwarf mutations express both mutation´s characteristics.

 

(Source: John E. Eberth, “Chondrodysplasia-Like Dwarfism in the Miniature Horse”, University of Kentucky)

 

D3/D2
D3/D2

ACAN D4 Genotypes (viable)

(=21 base deletion in NCBI exon 15)

No samples of homozygous D4 mutation were acquired. When D4 allele was present with D1 allele the results are lethal

 

·        Growth was disproportionate, exhibiting severe short stature with a short barrel misshapen and more pronounced than D2/D2 and D3/D3,

·        Roaching of spine is more pronounced and severity progresses with age,

·        Barrel appears even more shortened due to curvature of spine

·        Variable pain and stiffness of hip and limbs are progressive

·        Craniofacial structures are disproportionately large head with pronounced frontal bone domed prominence, enlarged eyes and orbit with a low and shortened nasal bone with some having a retruded muzzle and under bite with varying severity

·        Airway obstruction is evident early and progressive,

·        Limbs are rhizomelic in length with bowing and joints are enlarged at birth with limited joint mobility,

·        Flexion contractures of hips, small pelvis with severe rotation (goose rump),

·        Severely shortened neck is noticeable from birth that is almost nonexistent

·        Motor milestones are often delayed secondary to joint deformities

·        Joint contractures and roach back progress quickly with age

·        Progressive and painful joint enlargement can be accompanied by flexion contractures in all limb joints causing abnormal hoof growth very early

·        Muscle atrophy results from disuse.

 

(Source: John E. Eberth, “Chondrodysplasia-Like Dwarfism in the Miniature Horse”, University of Kentucky)

 

The pics above are showing the following dwarf types: D2/D4, D3/D4


Gallery (These pics are showing types of ACAN-dwarfism through all colours in Miniature Breeds)

I appriciate each Pic which I can use for this homepage. If you want to send me a pic an your ACAN dwarf please send them to zwergenwuchs@mail.de. Thanks a lot!


Contact

Mrs. Marleen Binder

zwergenwuchs@mail.de

RIP: Daisy, skeletal atavism dwarf, 2006
RIP: Daisy, skeletal atavism dwarf, 2006