Congenital and Hereditary Defects Flashcards
Genetic diseases of the epidermal basement membrane are collectively known as what?
Epidermolysis bullosa (EB)
EB Simplex (EBS - suprabasal) in dogs
Suprabasal EBS has been recognized only once in animals.
Mutations of PKP1 leading to plakophilin-1 deficiency were found recently to cause the ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retrievers
EBS in Friesian-Jersey cattle
EBS (basal) was diagnosed in 17 newborn Friesian-Jersey crossbred calves derived from sire-testing herds in New Zealand.
The trait was linked to a chromosomal region close to that containing KRT5.
All affected calves were heterozygous for the mutation, thereby confirming the autosomal dominant nature of the disease.
EBS in a quarterhorse
A single young quarterhorse foal was presented with erosions on the withers, back, chest and upper forelegs in Australia.n this foal, Indirect IF revealed the absent expression of plectin and the perinuclear condensation of keratin-14.
In this foal, clinical signs, microscopic and ultrastructural findings are suggestive of the diagnosis of a basal EBS. The lack of immunoreactivity for the intracellular protein plectin suggests that a mutation in the equine PLEC gene could cause skin lesions and laminitis in this foal.
EBS in Eurasier dogs
In these dogs, an homozygous nonsense mutation in the exon 27 of the PLEC gene, which was predicted to result in plectin truncation to 1,315 rather than its normal 4686 amino-acids
Junctional Epidermolysis Bulls (JEB)
At this time, in animals, JEB has been found to be caused by mutations of either LAMA3, LAMC2 and ITGB4 (Table 1). One kitten was also reported with a defective laminin beta-3 immunostaining.6
JEB in German shorthaired pointers
- Its mode of transmission is believed to be autosomal recessive.
- A sex predisposition has not been observed.
- In these dogs with JEB, lesions appeared usually within weeks of birth, but sometimes they developed after a few months of age.
- Electron microscopy not only confirmed that clefting occurs above the lamina densa, but it also revealed that the number and morphology of hemidesmosomes appeared similar to that seen in normal canine individuals.
- the defect of LAMA3 in affected dogs = reduced secretion of the alpha-3 chain and inadequate laminin-332 assembly.
JEB (“epitheliogenesis imperfecta”, EI) in American saddlebred horses
- Equine “epitheliogenesis imperfecta” is now known to represent lethal JEB in this species
- It is transmitted as an autosomal recessive trait in this breed
- Sequencing of LAMA3 in foals with EI revealed a large deletion base pair that eliminates exons 24, 25, 26 and 27 from the laminin alpha-3 chain
JEB of Belgian blue cattle
- Sequencing of this region revealed a missense mutation creating a premature stop codon (p.R2609*) in the exon 60 of the LAMA3 gene.
- This mutation, which results in a 22% shortening of the laminin alpha-3 chain, was found to be causative of JEB in this breed.
JEB of draft horse breeds of European origin
- the mode of transmission is consistent with an autosomal recessive inheritance
- In affected draft horses of these various breeds, skin lesions appear within days of birth and consist of severe ulceration pressure points of the limbs, in the oral cavity and at mucocutaneous junctions of the mouth, anus and vulva.
- Studies confirmed the decreased secretion of the laminin gamma-2 chain. These results were consistent with a failure of laminin-5 (Lm332) assembly and indicated the equine LAMC2 as the suspected causative gene of this disease.
JEB in a cat
- One domestic shorthaired was found to exhibit pinnal erosions, oral ulcerations and severe onychomadesis.
- Histopathology, electron microscopy and/or indirect immunoperoxidase revealed subepidermal clefting with the lamina densa remaining attached to the floor of the vesicles.
- Indirect immunofluorescence revealed reduced staining for laminin-332’s gamma- 2 subunit in one cat, suggesting that a mutation in LAMC2 might have been present
- A second cat with a phenotype and histopathology identical to that of the cat described in section exhibited a decrease in cutaneous laminin beta-3 immunostaining, suggesting a mutation in LAMB3, which was not characterized further.
JEB in German black head mutton sheep
- autosomal recessive transmissio
- immunohistochemical staining for collagen VII was similar in affected and control lambs while staining for laminin-332 was reduced in diseased lambs.
- Linkage and genomewide association studies mapped the trait to a region containing the LAMC2 gene.
- This mutation is located within the alpha-helix of laminin gamma-2 and it shortens the chain 13 codons downstream of the deletion. It is predicted to alter the assembly of laminin gamma-2 to the other two laminin chains thereby leading to altered function of laminin-332
JEB in Danish Herefords
The whole genome sequencing of one affected calf revealed a 2,433 base-pair deletion on chromosome 16, which caused the complete removal of the exon 1 of LAMC2 containing the start codon and the first 79 coding bases of the mRNA transcript.
JEB in Charolais cattle
- Antigen immunomapping was consistent with clefting occurring in the lamina lucida of the basement membrane, which established the diagnosis of JEB.
- The immunoreactivity for the alpha-6 integrin chain, but not that of laminin-332 chains or collagen XVII, was reduced in this calf compared to nonaffected bovine controls.
- These observations suggested that a mutation in the ITGA6 or ITGB4 genes encoding the integrin alpha-6 and beta-4 pair could be the cause of lesions in this patient
JEB in Churra sheep
- A genome-wide study revealed the association of the trait with an homozygous region of chromosome OAR11.
- A four base-pair delation was eventually found in the exon 33 of the ITGB4 gene.
Dystropic Epidermolysis Bulls
There are several subtypes of DEB in humans, all are due to varying mutations of COL7A1 that encodes for collagen VII. Over the last four decades, DEB has been reported sporadically in many animal species
DEB in white Alpine sheep
- Electron microscopy established that clefting occurred in the sublamina densa and that well-formed anchoring fibrils could not be found.
- Immunomapping confirmed clefting below the lamina densa, thereby establishing the diagnosis of DEB.
- Immunoblotting for collagen VII confirmed the absence of this protein in affected sheep tissue.
DEB in a Persian cat
- Microscopic examination of skin biopsies revealed dermo-epidermal separation without keratinocyte cytolysis.
- Collagen IV immunostaining revealed the lamina densa at the top of the clefts, which confirmed the diagnosis of DEB.
- Immunostaining for collagen VII revealed a markedly reduced intensity of basement membrane fluorescence in this cat’s skin compared to normal feline tissue
DEB in Assaf sheep
Immunostaining for collagen VII was negative in affected lambs.
DEB in Rotes Höhenvieh cattle
- Genomewide homozygosity mapping was consistent with a COL7A1 mutation.
- While it was unclear if the shortened protein was expressed, it was found to miss several collagen triple helix repeats that likely impaired collagen VII function and anchoring fibril formation.
DEB in Vorderwald cattle
Whole genome sequencing from two affected calves revealed an haplotype association on chromosome BTA22. Among candidate causal variants, the same mutation in COL7A1 as that seen in the Rotes Höhenvieh cattle.
DEB in golden retrievers
- Screening for genetic mutations demonstrated a homozygous nucleotide change in COL7A1, which co-segregated with the disease in affected individuals.
- This mutation predicts the substitution of a glycine into a serine (1906G-to-S) within the collagenous triple helix of collagen VII
Suprabasal Acantholytic Epidermolysis Bullosa in Bovidae
- Three separate occurrences of a congenital hereditary disease resembling human suprabasal EBS have been reported in bovidae: the so-called “familial acantholysis” in Angus calves 5, “hereditary suprabasal acantholytic mechanobullous dermatosis” in Brazilian Murrah buffaloes 6 and an unpublished report of “acantholytic EB” in Texan Brangus calves.
- Clinical signs occurred shortly at or within a few weeks of birth, and they consisted of erosions and ulcers with hair loss occurring principally on pressure points of all limbs and, occasionally, the tail.
- Light microscopy of affected skin biopsy specimens revealed suprabasal acantholysis resulting in intra-epidermal blistering
- Desmosomes were absent or rare in basal keratinocytes, and this lack of desmosomes was associated with the detachment of keratin intermediate filaments from desmosomal plaques.
Hereditary blistering dermatosis Chesapeake Bay retriever (CBR)
- Present at birth and puppies euthanized by 3 months of age
- Histopathology revealed a severe disintegration of the epidermis with extensive acantholysis of suprabasal keratinocytes.
- The immunomapping profile of affected dogs was consistent with lesion formation due to an absence of PKP1 leading to a detachment of desmoplakin from the desmosomal plaque and its retraction to the cell cytoplasm.
Darier Disease in Dogs
- In humans, autosomal dominant mutations of the genes encoding the calcium pumps SERCA2 cause Darier (DD) and Hailey-Hailey diseases.
- In DD, there is prominent suprabasal acantholysis resulting either from the impairment of desmosomal function or from secondary alteration in epidermal differentiation.
- Disintegration of the intermediate filament cytoskeleton also is associated with the formation of dyskeratotic keratinocytes named either “corps ronds” (e.g. round bodies) or “grains”.
- In HHD, there is widespread acantholysis in suprabasal epidermal layers, and ultrastructural examination also reveals perinuclear keratin rings following the detachment of filaments from desmosomal plaques.
- While most cases of DD and HHD have been convincingly associated with mutations of the ATP2A2 and ATP2C1 genes encoding SERCA2 and SPCA1,
- Published reports suggest the existence of a dermatosis in an English setter and its crossbreds, which resembled DD in humans
Idiopathic and presumably hereditary facial dermatosis of what breed of cat has been described?
Persian and Himalayan Cats
Affected cats have a. dirty face with adherent black exudate on skin and distal portions of the hair shafts.
Ulcerative Nasal Dermatitis is a rare disease and restricted to what breed of cat?
Bengal cats
Most cases have been recognized in Sweden.
Hyperkeratosis and fissuring are common clinical signs.
Ichthyosis in the Golden Retriever revealed numerous ______ retained in the epidermis, suggesting that a delay in their degradation is response for the clinical disease.
corneodesmosomes
Ichthyosis affected Norfolk Terriers show decreased staining for ____ in the epidermis secondary to a mutation in the gene encoding ____.
keratin 10
K10
Ichthyosis in the JRT, the thin cornfield envelope is associated with a mutation in the ____ gene. These dogs have a decreased free fatty acid and acyleramide levels and increased ceramics III levels in the stratum corneum.
TGM1
Ichthyosis in the CKCS indicates epidermal _____ with altered numbers and morphologic atypic of keratohyalin granules, curvilinear structures in the stratum corneum and alteration in the intercoryneocyte spaces.
hyperproliferation
What is the difference between Norfolk Terrier presentation of Ichthyosis compared to CKCS?
NT have the hyper pigmented scaly skin typical of ichthyosis but develop blisters and erosion in areas of mild skin trauma.
CKCS have a harsh crimpy coat with little or no visible scale early in life. The vibriassae are also affected. Their claw are often abnormal. Addiiotnally, these dogs ALSO have KCS.
What disease is a congenital hereditary disorder of cornification that has been described in multiple Rottweiler puppies, Siberian husky puppy and several Labrador Retrievers?
Follicular parakeratosis
All cases have occurred in females suggesting this is an X-linked trait.
Psoriasiform-lichenoid dermatosis is rare and recognized only in what breed? It is proposed to be an exaggerated response to staphylococcal infection.
English Springer Spaniels
Describe the histopathology of Psoriasiform-lichenoid dermatosis in English Springer Spaniels
Superficial perivascular to interstitial dermatitis with psoriasiform epidermal hyperplasia and areas of lichenoid interface dermatitis, intraepidermal microabssess (containing eosinophils and neutrophils) and ‘monro’ microabssess.
What syndrome affects the backs of some miniature schnauzers and it typified by multiple comedones that may become crusted, non-painful papule?
Schnauzer Comedo Syndome
This syndrome may be a developmental dysplasia of hair follicles,
What disease causes severe hyperkeratosis by 6 months of age. all pads of all feet are involved and an autosomal recessive inheritance has been identified in Irish Terriers and Dogue de Bordeaux.
Foodpad hyperkeratisis
Severe hyperkeratosis, fissures and secondary infection can occur and cause lameness.
Treatment is symptomatic.
What uncommon condition causes hyperkeratosis of the dorsal aspect of the nasal planum of the Labrador retriever or their crosses (suspected autosomal recessive model of inheritance)?
Hereditary Nasal Hyperkeratosis of the Labrador Retriever
What is the classical histopathologic findings in Hereditary Nasal Hyperkeratosis of the Labrador Retriever?
Mild to marked parakeratotic hyperkeratosis, moderate lymphocytic and neutrophilic exocytosis, and multifocal serous lakes within the upper epidermis. A superficial interstitial interface dermatitis is present.
What disease is a congenital inherited discontinuity of squamous epithelium and is considered autosomal recessive in cattle, horses, sheep and pigs.
Aplasia Cutis
**Histologically, ulcerated areas are distinguish by complete absence of epidermis, hair follicles and glands.
What is a neutral tube defect resulting from incomplete separation of the skin and neutral tube during embryonic development?
Dermoid Sinus
It is a tubular indentation of skin extends from the dorsal midline downwards and can extend to various depths.
Type 1 - End on the supra sinus ligament/nuchal ligament
Type 5 - Dermoid cyst
Dermoid Sinus has be reported mostly in what breed? The autosomal DOMINANT mutation involves what factors?
Rhodesian and Thai Ridgeback
FGF3, FGF4 and FGF19
(rare in cat but Burmese is overrepresented concurrently with neurologic deficits)
How is a dermoid sinus confirmed diagnostically?
fistulogram
Epidermolysis Bullosa Simplex is the mot superficial disorder, with cleating occurring in the ____ layer of the epidermis.
basal
In ______ disease, blisters form within the lamina lucida of the dermoepidermal basement membrane. Ulcerative lesions are most marked over bony prominences of the face, pinna, pressure points on the limbs and food pads.
Junctional EB
**lesions can also arise in the oral cavity and claws may be abnormal.
In what breed is JEB us autosomal recessive associated with a decreased expression of what structure?
GSHP
laminin 332 (laminin 5)
This condition is an autosomal recessive trait associated with decreased expression of collagen VII due to mutation in the COL7A1 gene.
Dystrophic epidermolysis bullosa
** In all animals skin biopsy showed a sub-basilar DEJ separation with the separation occurring BELOW the lamina densa with a reduction in the number of anchoring fibrils.
What disease is a hereditary, idiopathic, inflammatory disorder of the skin and muscles of your collies and Shetland Sheep Dogs?
Familial Canine Dermatomyositis
Autosomal DOMINANT
The most common sign in dermatomyositis of myositits is what finding?
asymptomatic atrophy - especially the muscles of mastication and distal limbs.
Describe histopathology of dermatomyositis
Scattered hydropower denervation of basal cells. Apoptotic basal cells (Civatte bodies) occasionally are visible. With marked hydropic degeneration - clefting may form. Dermal inflammation can be absent. Follicular atrophy and perifollicular fibrosis are common findings and may be the only findings in chronic lesions.
Muscle biopsy may show mixed inflammatory exudates accompanies by muscle fiber necrosis and atrophy.
Describe the needle EMG abnormalities in dermatomyositis
positive sharp waves and fibrillation potentials in the muscles of the head and of the distal extremities.
***CK levels may be increased as a side note on blood work
The magnitude of the elevations in ______ and _____ levels correlates with the severity of the Dermatomyositis.
IgG and immune complex levels
The skin lesions of dermatomyositis are worsened by what two factors?
trauma and sun exposure
**amyloidosis occurs in some chronically effected cases
What disease is an autosomal DOMINANT disorder of cellular cohesion among keratinocytes. The condition is due to mutations in the gene encoding calcium pumps, which impart desmosomal function or epidermal differentiation.
Canine Darier’s Disease
Darier’s disease has been prorated in what breed and their crosses and is associated with abnormal calcium homeostasis due to depletion of SERCA2-gated stores?
English Setters (autosomal dominant)
**also reported in a Doberman Pincher
What are the common clinical features of Dariers disease?
Lesions occur in dogs around 6 months of age and occur over pressure points on the limbs.
What disease is recognized as an autosomal recessive trait in Chesapeake Bay retrievers. It is characterized by superficial blisters and erosions shortly after birth in areas of trauma.
Ectodermal Dysplasia - Skin Fragility Syndrome
In Ectodermal Dysplasia - Skin Fragility Syndrome, what do the histopathology and ultrastructural studies reveal?
Biopsies show extensive acantholysis of suprabasilar keratinocyte and US show a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments.
What does immunostaining for ectodermal dysplasia in dogs reveal?
Immunostaining revealed NO plakophilin-1 and changes in distribution of desmoplakin and K10/K14.
What breed is Trichorrhexis Nodosa been recognized in and how does it present?
Golden Retrievers - acquired defect in which external installs damage the cuticle and weaken the hair shaft.
Diagnosis of trichoptilosis can only be confirmed by what diagnostic?
trichography
What is an unusual hair shaft disorder wherein the medulla vacillates spontaneously. What breed has this been identified most commonly in?
Medullary Trichomalacia
GSD
What does trichography of medially trichomalacia reveal?
hairs have longitudinally split in the middle of the hair shaft and the medulla is depigmented and vacuolated. Biopsies reveal catagenization of most hair follicles, some of which contain increased numbers of dead keratinocytes in the ORS.
What is a condition in which the curvature of the hair follicle leads to flattening and rotation of the hair shaft. It has been reported in kittens and some bull terriers.
Pili Torti
Shaft disorder occurs in what breed of cats and what is affected?
Abysinnian; Only whiskers and primary hairs are affected with an ‘onion shaped’ swelling at the tip of the hair.
Spiculosis a rare disorder of what breed of dog? Affected dogs will have multiple hard, brittle follicular spicules most commonly found on the lateral hock region.
Kerry Blue terriers (young/intact/male)
This defect results in an amorphous mass of keratin that is shaped into a spicule by the ORS and follicular wall.
What are the two examples of hairless dog breeds and what is the mutation they have?
Mexican Hairless Dog, Chinese Crested
Autosomal dominant frameshift mutation in FOXI3; but is not due to an EDAR (Ectodysplasin A receptor) mutation.
American Hairless Terriers have a autosomal recessive hairless trait.
Congenital hypotrichosis in cats is an autosomal recessive trait in what two breeds?
Birman and Siamese
affect Burmese cats have no whiskers, claws or papillae on their dogs. No thymus was found at necropsy.
What is the distribution if hairless in dogs with ectodermal dysplasia? What is gene affected and mode of inheritance?
Symmetrical hairless affecting the frontotemporal, sacral, abdominal, and proximal limb regions are hairless, whereas other areas of hypotrichotitc.
**X-linked autosomal recessive. These dogs can have abnormalities with dentition and glandular formation. The condition is due to a mutation in the EDA gene.
What disease is a familial disorder of puppies with black or multicolored haricots. The condition and color dilution alopecia area associated with abnormal melanization of the affected hairs.
Black Hair Follicular Dysplasia
Black Hair Follicular Dysplasia is due to a mutation within or near what gene?
MLPH (Melanophilin)
*Thought to be autosomal recessive
Describe histopathology of Black Hair Follicular Dysplasia
Specimens from non-black hairs are normal, whereas black areas show dumped melanin in epidermal and follicular basal cells and hair matrix cells. Large melanin granules (macromelanosomes) are visible within hair shafts, and large clumps of free melanin. The normal architecture of hair shafts is obscured, with unclear definition between cuticle, cortex and medulla.
What are the three syndromes and breeds of patterned baldness in dogs?
Pinnal alopecia of Dachshunds.
Ventral/lateral neck alopecia in American Water Spaniels
Caudal thigh alopecia of Greyhounds (Bald thigh syndrome in Greyhounds is lateral versus caudal)
Pre/post auricular alopecia/ventrum/caudal thighs in Dachshunds and Boston Terriers.
Describe histopathology in patterned baldness
Patterned baldness is characterized by miniaturization of the hair follicles and hair shaft with normal adnexal structures. Follicles are shorter and thinner, have smaller hair bulbs and produce fine hair shafts.
What syndrome occurs in some dogs with blue or fawn coat colors. These colors are fukution of black or brown, respectively, and result from influence of coat color genes at the _____ of the ____ gene and possible others,
D locus, MLPH
What process is important for pigment transfer to the hair. In color dilution alopecia, dendritic extension is abnormal. All affected dogs have irregularities in melanin transfer and storage.
Cytophagocytosis
Mature or stage ____ melanosomes are stored irregularly in hairs, and epidermal keratinocytes and vacuolization of melanocytes in some hair bulbs suggests a generative process in color dilution alopecia.
IV
In color dilution alopecia, in what breed is the cuticle of affected hairs normal except at the point of melanin clumping. This is different than what two breeds where defects of the cuticle were detected in affected and normal hairs.
Doberman pincher
Yorkies and Dachshunds
Cats with blue or cream-colored coat carry the ____ gene. As in the dog, this gene is expressed by clumping of melanin in the follicular epithelium and hair shafts but rarely is associated with dysplastic changes in the hair follicle and hairs themselves.
Maltese
Canine Flank Alopecia - hair loss usually occurs in the late _____ or early ____; which breeds does the hair loss become permanent.
late Fall/early Spring
Boxers and English Bulldogs
Describe follicular dysplasia in Siberian Husky and Malamute
Multiple dogs in a litter can be affected, and at 3 to 4 months of age, the guard hairs on the trunk are lost and coat turns red. In malamutes, the onset of signs may not be seen until 3 to 4 years of age.
**On biopsy - Huskeys have tortuous glassy membranes and follicular epithelial disarray.
Describe follicular dysplasia in Airedale Terrier, Boxer, English Bulldog, Pitbull, Wire-haired Griffons and Affenpinchers
Hair loss beings between 2 and 4 years of age and is restricted to the flank and/or saddle regions in some dogs, the hair loss persists, whereas cyclic loss and regrowth occurs in other dogs.
Describe follicular dysplasia in Doberman Pinschers, miniature pinschers and Manchester terriers
Black or red dogs can be affected, and hair loss is noted between 1 and 4 years of age. Hair loss begins in the flank region and processes slowly to involve the caudal dorsal and entire flank region.
Describe follicular dysplasia in Irish Water Spaniels, Portuguese Water Dogs and Curley noted Retrievers
This hair loss is due to hair fracture*. Alopecia is usually not recognized until 2 to 4 years of age.
Hair loss occurs first over the caudal dorsal region.
A dominant mode of inheritance is suspected in the Irish Water spaniel. Mutations in the R-spondin 2 gene are probably the cause in the Portuguese Water Dog.
** In PWD - show vacuolar alteration of the hair follicle inner root sheath and hair matrix, with ultimate dissolution of the hair matrix.
Describe follicular dysplasia in Weimaraners
Hair loss began between 1 and 3 years of age. Head and limbs were spared. Not all diluted hairs in these dogs were affected - so unlikely color dilution alopecia.
What is a variant of follicular dysplasia that is recognized worldwide in the Rottweiler?
Follicular lipidosis
Clinical signs occur within the first 9 months of life. The presenting complain is hair loss in the mahogany point of the face and feet.
Describe histopathology of follicular lipidosis
Skin biopsy shows severe swelling of the matrix cells of anlagen hair follicles; this swelling is swelling is due to accusation of lipid with the cells cytoplasm.
Melanoderma and alopecia in what breed is well recognized but poorly studied syndrome that appears to be decreasing in incidence.
Yorkies
Marked alopecia and hyperpigmentation over the bridge of the nose, pinnae and tail (occasionally feet).
**Three dogs treated with GH regrew hair but lost it again
In cats, this is an autosomal recessive disorder occurring ONLY in Persian cats with with blue-smoke hair color and yellow eyes. Affected cats have giant lysosomes in the cytoplasm of neutrophils and macrophages (look like large eosinophilic granules).
Chediak Higashi Syndrome
This disease is characterized by increased susceptibility to infection, partial oculocutaneous albinism, photophobia and bleeding disorders. These cats are at an increased risk for infection - most cases of dermatophytic pseudomycetoma have occurred in smoke colored Persian cats.
What disease is a lethal autosomal recessive syndrome in which collie puppies are born with silver-gray hair coat that differs from the normal tricolor coat. In the dog, this syndrome is associated with a mutation of the gene on _________.
Canine Cyclic Hematopoiesis (Gray Collie Syndrome)
Coding dog adaptor protein complex 3 (APB3)
*Another feature is a cyclical neutropenia that cycles every 10-12 days until death. Usually dogs don’t survive past 6 months.
**Another differential is the dominant or Maltese gray collie and a transient dilution called ‘powder puff’
Acquired Autotrichia occurs in what breed?
Miniature Schnauzers
These cases usually start in warm weather and patchy hair color changes occur over the dorsal thorax and affected hairs are golden in color (guard hairs).
What is the group of inherited connective tissue diseases characterized by excessive fragility and hyper extensibility of the skin.
Cutaneous Asthenia, Ehlors-Danlos Syndrome
The tensile strength of the skin of affect dogs with Cutaneous Asthenia is reduced by ____ and in cats it is reduced by _____.
40 fold, 10 fold
In canine RECESSIVE cutaneous asthenia, biochemical studies have demonstrated a ______ defect in which there is decreased activity of procollagen peptidase and an accumulation of partially processed type I procollagen containing N-termal propeptides.
procollagen processing
** collagenase activity is typically increased 2.5 times above normal levels.
In canine DOMINANT cutaneous asthenia, the defect can cause focal of diffuse changes in dermal collagen and results from abnormalities in ________.
he packing of collagen into fibrils and fibers owing to mutations in structural proteins.
Biochemical studies in dominant cutaneous asthenia show what changes to dermatan sulfate, HA and glucuronic acid levels.
decreased dermatan sulfate
increased HA levels
altered glucuronic acid levels
In cutaneous asthenia, some animals may have concurrent _____ and ______,
joint laxity ocular changes (microcornea, schlerocornea, lens lunation and cataracts)
How do you calculate the skin extensibility index?
vertical height of skin fold/body length x 100
In affected dogs, skin extensibility is greater than 14. 5%
In affected cats, it is greater than 19%
What are the histopathologic findings in cutaneous asthenia?
Skin biopsy may reveal striking abnormalities or normal skin. Inability to detect histologic findings is normal in the cat. When changes are present, collagen fibers may appear more eosinophilic, blurred and disorganized. Collagen fibers may form irregularly sized bundles, improper interweaving and be surrounded by mucin.
Masson Trichome stain is useful for collagen disorders.
Because ____ is necessary in collagen synthesis, supplementation may be beneficial for treatment of cutaneous asthenia.
Vitamin C
What disorder is found in German Shepherds characterized by clinical and histologic features of the familial vasculopathy of GSD. Swelling, depigmentation, ulceration and crusting can develop on one of all of the pads. Biopsy revealed deep dermatitis focused around multifocal areas of collagenolysis.
Disorder of the Footpads in German Shepherds
Usually ulcers heal by one year go age.
Some dogs have developed renal amyloidosis and died.
Metatarsal fisulation. is an uncommon disorder of what two breeds?
GSD and Weimeraners
Collagneous Nevi (multiple) are found in what breed?
GSD
What condition is known as nodular dermatofibrosis and the skin lesions are a cuteanous marked for renal cystadenocardinomas or uterine leiomyomas.
Multiple Collagenous Nevi
Multiple Collagenous Nevi is due to a mutation in what gene?
BHD gene (autosomal DOMINANT)
What is a hereditary disorder of elastic fibers in human characterized clinically bu skin that is pendulous, flaccid, hanging in folds, and seemingly excessive compared with the individual body size? Histologically, there is progressive loss of elastic fibers.
Cutis Laxa
Familial Vasculopathy of Beagles
A systemic necrotizing vasculitis of small to medium sized arteries is well described in a colony-bred beagles. Signs occur early in life (4 - 10 months of age). Signs are cyclic and include fever, lethargy, and hunched stance. Skin lesions are rare but purupura occasionally is seen.
Familial Vasculopathy of German Shepherds
Affected dogs have signs at 4-10 weeks and signs often occur 7 to 10 days after vaccinations.
Dogs are lethargic and have lymphadenopathy.
The bridge of the nose is swollen and crusted, ulcerated lesion s occur on the ear margins, nasal plant and tail tip.
All food pads are swollen with varying depigmentation.
Biopsy shows lymphohistoplasmacytic dermatitis surrounding postcapullary venues and collagen bundles.
*possible autosomal recessive role of inheritance
Familial Vasculopathy of Greyhounds
Approximately 75% fo cases have only skin lesions, whereas the remainder have renal plus cutaneous signs.
Skin lesions occur primarily over the tarsus, stifle or inner thigh and are sharply demarcated deep ulcerations.
Biopsy shows a thrombosis of arterioles, venues and capillaries.
This is probably caused by verotoxin (Shira-like toxin) from E.coli in raw food.
aka Alabama Rot
Familial Vasculopathy of Scottish Terriers
Affected dogs have bilateral nasal discharge at 3 to 4 weeks of age followed by progressive ulceration and destruction of the nasal planum, nostrils and nasal mucosa.
**probably autosomal dominant
Familial Vasculopathy of JRT
Typical lesions occurring with small vessel vasculitis, these dogs have alopecia and discretely ulcerated and crusted skin lesions of the bony provinces of the head and extremities, V shaped necrotic areas of pinnae and punctate ulcers of the foot pads.
Biopsy typically shows apoptosis of the basal layer of the epidermis, pigmentary incontinence, leukoclastic vasculitis, and ischemic degeneration of hair follicles.
Familial Vasculopathy of Saint Bernards
This is described as arteritis of the nasal philtrum.
What disease has been reported as an inherited autosomal recessive trait that produces a lethal snfrom in bull terriers? A similar syndrome was recognized in Pharaoh hounds. The specific cause of condition is unknown; however, affected dogs have defective zinc and copper metabolism.
Acrodermatitis
They do not respond to zinc supplementation
Affected dogs with acrodermatitis have altered expression of 13 liver proteins, They also have a fourfold increased expression ______, ______, ______ and ______.
haptoglobin
glutamine synthase
prohibition
K10
Describe the histopathology in acrodermatitis
Histopathology shows diffuse parakeratotic hyperkeratosis with focal crusting and pustules. The superficial epidermis may show laminar pallor as occurs in SND but the keratinocytes are viable and not generating.
**Lymphocytes are severely reduced in T cell areas of cymoid tissues.
What is an autosomal recessive metabolic disease similar to pseudotemper in minks?
Tyrosinemia
Treatment is diet manipulation; low in tyrosine and phenylalanine.
In the one case reported of Tyrosinemia in in a German shepherd. Tyrosine levels were increased due to a deficiency of _________.
cytosolic hepatic tyrosine aminotransferase
The pathologic changes are due to tyrosine crystals deposited in tissue. However, most skin lesions do not have crystals. Instead, there is an increase in tonofibrils and increased numbers of keratohyaline granules in the granular layer.
**Tyrosine is known to influence the number of microtubules in the tonofibrils.
In Tyrosinemia, histopathologic examination of the ulcerated skin revealed pyogranulomatous inflammation associated with large dark-brown granules of tyrosine surround by an eosinophilic amorphous material that resembled the Splendore-Hoeppli reaction. The granules gave a positive orange reaction when stained with the _____ for tyrosine.
Millon reaction
Mucopolysaccharidosis (inherited disorder of GAG catabolism) is most common in what breed? Characterized by downward drooping of pinnae.
Siamese
What syndrome is an hereditary sensory neuropathy of dogs that results in progressive mutilation of the distal extremeties?
Acral Mutilation Syndrome
In Acral Mutilation Syndrome, pathologic changes are identified at the level of the ________. The nerve cell bodies of the sub capsular angle zone are decreased in number and the neutron mantle is decreased in thickness. The number of small neutrons in the affected ganglia are disproportionately increased in affected dogs.
primary sensory neuron
In Acral Mutilation Syndrome, the spinal cord changes occur in the ____, where reduced fiber density correlate well with the loss of pain perception that is clinical apparent.
dorsolateral fasciculus
Oral eosinophilic granuloma is an idiopathic condition reported most commonly in what two breeds?
Siberian Husky and the CKSP.
What syndrome is associated with congenital abnormality of the caudal occipital bone that cures compression of the cervicomedullay junction with alteration in the CSF flow.
Caudal Occipital Malformation Syndrome (COMS)
What is a component of the normal dermal ground substance. Excessive accumulation of this can be focal, regionalized or general and can occur in hypothyroidism, acromegaly, alopecia mucinosa, dermatomyositis or discoid lipid erythemaosus.
Mucin
What are the three main features of Shar Pei mucinosis?
- distorted lymphatics
- massive accumulations of HA
- Mast cells of the ‘chymase-carboxypeptidase subtype’
What is the most common cutaneous manifestation of mastocytosis and is characterized by variably symptomatic small, yellow-tan to reddish brown macule or papule,
Urticaria Pigmentosa
