Keratinization Defects Flashcards
Ichthyosis
Several types of ichthytosis occur in animals and people. Clinical signs include accumulations of dead skin cells resulting in thick, dry scales that in the most severe forms resemble fish scales adherent to the skin surface.
Congenital forms of ichthyosis are due to primary defects in the formation of stratum corneum. Mutation in keratin genes result in epidermolytic forms of ichthyosis, while mutations affecting the production of lipids, non-keratin proteins or desquamation result in non-epidermolytic forms of ichthyosis.
Epidernolytic Ichthyosis
Light microscopy findings include vacuoles and lysis of keratinocytes in the stratum spinous and stratum granulosum, hypergranulosis and hyperkeratosis. Dog breeds reported to have epidermolytic forms of ichythyosis include Norfolk terriers, Rhodesian ridgebacks, Labrador retrievers and CKCS.
Ichthyosis: Norfolk Terriers
Identified as a mutation of keratin 10 production and a genetic test is available through PawPrint genetics. it is autosomal recessive and affect dogs have epidermal fragility that results in the superficial epidermis sloughing easily. Intertriginous areas may be severely affected. The food pads, hair and teeth are normal.
Non-epidermolytic Ichthyosis
Many dog breeds have been reported to have non-epidermolytic ichthyosis including Jack Russel terriers, Australian Terriers, Cairn Terriers, Norfolk terriers, American Bull Dogs, Golden Retreivers, Great Danes, and German Shepherds.
Ichthyosis: Jack Russel Terriers
Loss of function mutation in TGM1 that results in formation of a defective CE.
It is autosomal recessive and affected dogs have large, thick adherent scales on the body and in the ear canals, food pad hyperkeratosis, onychomalacia and a predisposition to secondary infections.
Genetic testing is available through University of Montreal.
Ichthyosis: American Bulldog
This is due to a mutation in NIPAL4 gene (nuclear interaction partner of ALK-like domain containing 4) that results in production of truncated protein = ichthyic protein with reduced lamellar body secretion, impaired formation of the confined envelope and accumulation of toxic metabolites in the skin. Affected puppies are noted as having a poor haricot shortly after birth, may have generalize white scales and the skin the ventral abdomen appears thickened with adherent brown scales.
Ichthyosis: Golden Retreiver
Due to a mutation in PNPLA1 (patina-lie phospholipase-1).
PNPLA1 codes for acylceramide and has a role in glycerophopholipid metabolism and cuteness barrier function. Affected puppies may have a rough haricot and scaling. The mutation has been found in over 50% of tested dogs in some countries (Switzerland).
Ichthyosis: GSD
Reprpoted in an intact female with scaling noted soon after birth. Genetic testing found a mutation in ASPRV1 gene that encodes aspartic peptize, retroviral-like1. Defects in ASPRV1 results in faulty processing of profilaggrin to filaggrin leading to wrinkled, dy, rough skin due to lack of normal aggression of keratin intermediate filaments and deficiency of natural moisturizing factors.
Ichthyosis: CKCS
Two types of ichthyosis has been reported.
Two littermates were reported with congenital ichthyosis in 1994.
More recently, a syndrome of Congenital Keratoconjunctivitis Sicca and Ichthyosiform Dermatatoses (CKCSID) has been reported in this breed.
Affected puppies have ‘dry eye’ from time of lid opening and frizzy haricoat. They also have dorsal scaling, footpad hyperkeratosis and deformed claw that may slough.
Genetic testing has identified a mutation of the FAM83H gene. Testing is available through Antagene.
Ichthyosis: Great Dane
Generalized gray to yellow scaling and skin wrinkles on their heads and legs.
Genetic testing found mutations of the SLC27A4 gene found on chromosome 9 affecting the proaction of fatty acid Transport Protein 4 (FATP4) that is an acyl-coat synthetase required for normal permeability barrier function.
Ichthyosis fetalis (Harlequin ichthyosis)
Several breeds of cattle have been reported with ichthyosis fettles. Affected calves are still-born or die within a few days following birth. Other features of this disease include microtia and eversion of the skin of the lips and eyelids.
Chianina
cattle with ichthyosis fettles have a H1935R substitution (mutation) gene ABA12. ABCA12 is an ATP-binding cassette transporter 12 protein and has a major role in transportation of lipids in the epidermis responsible for cholesterol efflux from keratinocytes.
65 mutations in this gene have been identified in people with harlequin ichthyosis. A mutation in ABCA12 was also identified in Shorthorn cattle affected with ichthyosis fetalis.
Ichthyosis congenita
Several breeds of cattle have been identified as suffering from a less severe form of ichthyosis termed ichthyosis congenita. Signs may be present at birth or appear within a few weeks with generalized hyperkeratosis and occasionally microtia, cataracts and thyroid abnormalities.
Naked foal syndrome
Akhal-Teke horses have been reported to have an autosomal recessive condition in which affected foals lack hair and have mild ichthyosis. Death occurs by 3 years of age. Genetic testing has found a nonsense variant of ST14 gene, which is serine protease involved in epidermal development.
Congenital ichthyosis in alpacas
One study of 68 alpacas with skin disease reported that 4.5% were diagnosed with ichthyosis.
Porcine model of harlequin ichthyosis
Ethylnitrosourea was used to create a pig model of harlequin ichthyosis with a mutation of the ABCA12 gene. Affected piglets have a severe hyperkeratosis and fail to thrive. This model has been used to study treatments.
Feeding acitretin to pregnant sows and newborn piglets results in improved phenotype and longer survival.
Treatments of Ichthyosis
Survival of children with ichthyosis has increased to 80% with the use of retinoids in treatment. Acitrentin has multiple effects on epidermal cell growth and differentiation and can up regulate the activity of ABCA6 to partially compensate for a lack of ABCA12. Other treatments that may help lessen the severity of clinical lesions include topical keratolytic, keratoplastic and emollient shampoos and sprays, topical retinoids, topical fatty acids and essential oils, topical retinoids and topical use of polyhydroxyacid gluconolacctone.
X-linked Cornification Defects
X-linked cornification defects have a dominant or semi-dominant phenotype. The skin lesions follow lines of Blaschko and may be more severe on one side of the body. Affected breeds have included Rottweilers, Siberian huskies and Labrador retrievers. Genetic analysis of an affect Labrador and her daughter found a structural defect in the NSDHL gene. Mutations in this gene are associated with CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) in people.
X-inked hypohidrotic ectodermal dysplasia
This has been reported in dachshunds - this is an X-linked recessive condition that results in mild clinical signs in heterozygous females and more severe signs in X-recessive male puppies.
This disease has been repotted in several breeds of dogs including miniature poodles, Belgian shepherds, Labrador retrievers, Bischon fries, GSD, whippet, cocker spaniel and mixed breeds.
Genetic analysis found a mutation of EDA gene (ectodysplasin A) - affected puppies and the dam had one base paid deletion in the EDA gene.
Follicular Parakeratosis and Mural Folliculitis
Follicular parakeratosis and mural folliculitis have been repotted in Labrador retrievers resulting in multifocal verruvous paupers and plaques, follicular cast formation , hair loss and comedones on the head, ears, abdomen, trunk and limbs. Some affected dogs improved following treatment with CSA and suggesting an immune-mediated disease.
Genetic testing was negative for NSDHL mutation.
Hereditary Nasal Parakeratosis
Labrador retrievers and greyhounds have been described with heredity nasal parakeratosis. Biopsy findings include marked parakeratosis with serum lakes between cell slayers of the nose.
Genetic studies have found a mutation in SUV39H2.
Familial Paw Pad Hyperkeratosis
Severe hyperkeratosis of pads of all feet develops in affected dogs by 9 months of age. Claws are very hard and fast growing and the haricot may be dull, dogs and less wooly than normal in affected Dromfohrlander dogs. This condition has also been reported in Irish terriers and Dogue de Bordeaux.
Genetic testingg has found a mutation in the FAM83G gene - other disease associated with this genetic mutation include mice with wooly haricots and CKCS with KCS and curly haricots
Antigen offers a genetic test for familial paw pad hyperkeratosis.
Primary seborrhea
It has been reported in American Coker spaniels, English singer spaniels, West highland white terriers, basset hounds, golden retrievers, American bulldogs ad Persian Cats. Epidermal cell kinetics were studied in cocker spaniels with affected dogs having epidermal turnover times of 8 days (normal is 21) and 3 to 4 times higher basal mitotic index. Autosomal recessive.
Exfoliative Cutaneous Lupus Erythematosus
GSHP have a hereditary condition termed ECLE that is inherited as a single nucleotide polymorphism on chromosome 18. Severe scaling starts o the face and ears and may become generalized. Affected dogs are painful and pruritus While early attempted at treatment were unrewarding, a case report showed a favorable response to treatment with mycophenolate. You could also try hydrocholoquine.
