14 day old male kitten Siberian cat (Felis cats)This cat is one of two littermates which were both born with fully developed hair coat. Beginning on day 11, both kittens lost most of their fur of the trunk with only a few hairs remaining on the head, the feet and tail. Both kittens died unexpectedly after unspecific clinical symptoms and one was submitted for pathological examination.

Gross Description:  

At necropsy the kitten had alopecia affecting mainly the trunk. The skin appeared normal in the alopecic and haired areas. The liver was slightly enlarged, friable and of smudgy yellowish color. All other organs had signs of congestion.

Histopathologic Description:

Histologically, the principal lesion is an abnormal structure of hair shafts. Hair bulbs including the dermal papillae are prominent and appear unchanged. Most parts of the inferior segments of the hairs are also regularly formed. Failure of proper keratinization is present in the upper third of the follicle resulting in a collapse of the medullary cavity with attenuated hair shafts becoming compact, hyaline masses. Large numbers of hair shafts fail to penetrate the epidermis. Instead, twisted, coiled, or sometimes "S"-shaped hair shafts are found within the isthmus or infundibular parts of follicles. Infundibular openings are dilated containing masses of lamellar keratin. Adnexal glands presented no obvious changes and were interpreted to be within normal limits. However, conclusive evaluation without an appropriate age-matched control tissue was considered difficult.

Few mild lymphoplasmacytic infiltrates are present in the superficial and perifollicular dermis. The mostly bilayered epidermis is unremarkable with multifocal to segmental mild orthokeratotic hyperkeratosis.

Morphologic Diagnosis:  

Haired skin: Trichomalacia (hair follicle dysplasia with defective hair shaft formation)



Contributor Comment:  

Lesions are consistent with dysplastic hair shaft formation. Several kinds of follicular dystrophies have been described in humans, domestic and laboratory animals.

The main clinical feature, alopecia occurring at or shortly after birth, can be induced by changes in either quantity or quality of hair shafts. Congenital changes are based most frequently on inherited abnormal morphogenesis and therefore are termed hair follicle dysplasias. There are several kinds of dysplasias, depending to the differentiation level of affected cells (single differentiated cell or progenitor cell). Accordingly, changes in related tissues like cutaneous appendages, nails or claws and teeth may occur.

The hair follicle with its product, the hair shaft, is a complex unit underlying tightly regulated cyclic changes.(6) Classification relies on differentiation between reduced hair follicle quantity and quality.(7)

Alterations in hair follicle quantity: Developmental reduction of hair placodes during organogenesis or defective morphogenesis with permanent loss of hair follicles can both lead to congenital alopecia. Delineation is often difficult because variable subsets of hair follicles are existent and are irregularly distributed over different body regions.

Aplasia of hair follicles with dental dysplasia affects more than one tissue derived from the ectoderm, mostly apocrine glands. Several forms have been reported in humans, various breeds of dogs,(10) mice,(2) and cattle,(1) with only few of the underlying signaling pathway defects characterized yet.(2) Aplasia of hair follicles without dental dysplasia with a dominant autosomal inheritance has been described in pigs.(7)

Alterations in hair follicle quality: Structural changes leading to reduced, defective or absent hair shaft production can be subdivided into those resulting from morphological changes of the hair follicle itself or those where morphologically unchanged hair bulbs form defective hair shafts.

Especially in the dog, several breeds are affected with hairlessness resulting from hair follicle dysplasia with defects in hair follicle development, for example Mexican(5) or Peruvian hairless dogs and Chinese crested dogs.(11) In contrast to horses with only rare reports, diverse forms have been described in various breeds of cattle. Some of these have already been characterized as autosomal recessive or dominant, partly lethal traits.(7)

Hair follicle dysplasia without defects in hair follicle development (trichomalacia) is classically represented by nude mice amongst few others.(8) Beside few breeds of cats, (e.g. Sphinx breed) and dogs,(7) mainly in man, numerous forms of trichomalacia have been observed.(4)

A special form of dysplasia affects the neuroectodermally derived follicular melanocytes which also contribute to regular hair follicle development.(3) Histopathological changes are specific and identical in both syndromes with formation of enlarged melanin granules in melanocytes and later aggregation of perifollicular melanophages.(7) Depending on the affected breed and coat colors, color dilution alopecia and black hair follicular dysplasia have been differentiated.(13)

The case submitted here fulfills the relevant criteria for hair follicle dysplasia without defects in hair follicle development (trichomalacia) because of the unchanged appearance of hair follicles. Further changes in ectodermderived tissues, like apocrine glands or teeth, were not observed. The occurrence in both animals of the litter is suggestive of an inherited genetic defect. The queen had been mated to the identical sire before, without any abnormality in the offspring. Unfortunately the littermate was not available for pathological examination and confirmation of similar changes in hair shaft formation.

Death of this kitten was attributed to acute hepatic failure with severe hepatocellular degeneration and lipidosis (peripheral lipomobilization syndrome) based on the results of pathological examination of all other organ systems, including histology.

JPC Diagnosis:  

Haired skin: Trichomalacia, diffuse, moderate.

Conference Comment:  

The main abnormality in this case is the presence of abnormal hair shafts with no cuticle, cortex, or medulla along with malformed keratin fragments. Trichomalacia refers to degeneration of the hair shaft and is manifest grossly as alopecia with broken hair shafts in the presence of normal follicles(12). In large animals, trichomalacia may be caused by certain nutritional deficiencies, such as copper, vitamin A, and folic acid; or by intoxication with hypervitaminosis A, D, or E, and with selenium and thallium toxicity(9). Conference participants discussed psychogenic alopecia, but this is ruled out because the patient is a kitten and the lesion is diffuse instead of sparse.


1. Drogemuller C, Distl O, Leeb T: X-linked anhidrotic ectodermal dysplasia (ED1) in men, mice, and cattle. Genet Sel Evol 35 Suppl 1: S137-145, 2003
2. Freire-Maia N, Lisboa-Costa T, Pagnan NAB: Ectodermal dysplasias: How many? American Journal of Medical Genetics 104: 84-84, 2001
3. Hume AN, Tarafder AK, Ramalho JS, Sviderskaya EV, Seabra MC: A Coiled-Coil Domain of Melanophilin Is Essential for Myosin Va Recruitment and Melanosome Transport in Melanocytes. Mol Biol Cell 17: 4720-4735, 2006
4. Itin PH, Fistarol SK: Hair shaft abnormalities--clues to diagnosis and treatment. Dermatology 211: 63-71, 2005
5. Kimura T, Ohshima S, Doi K: The Inheritance and Breeding Results of Hairless Descendants of Mexican-Hairless Dogs. Laboratory Animals 27: 55-58, 1993
6. Krause K, Foitzik K: Biology of the hair follicle: The basics. Seminars in Cutaneous Medicine and Surgery 25: 2-10, 2006
7. Mecklenburg L: An overview on congenital alopecia in domestic animals. Vet Dermatol 17: 393-410, 2006
8. Mecklenburg L, Tychsen B, Paus R: Learning from nudity: lessons from the nude phenotype. Experimental Dermatology 14: 797-810, 2005
9. Meckelburg L. Trichomalacia. In: Meckelburg L, Linek M, Tobin DJ, eds. Hair Loss Disorders in Domestic Animals. Ames, IA: Wiley-Blackwell; 2009:115-117.
10. Moura E, Cirio SM: Clinical and genetic aspects of X-linked ectodermal dysplasia in the dog -a review including three new spontaneous cases. Veterinary Dermatology 15: 269-277, 2004
11. Sander P, Drogemuller C, Cadieu E, Andre C, Leeb T: Analysis of the canine EDAR gene and exclusion as a candidate for the hairless phenotype in the Chinese Crested dog. Animal Genetics 36: 168-171, 2005
12. Tieghi C, Miller WH Jr, Scott DW, Pasquinelli G. Medullary trichomalacia in 6 German shepherd dogs. Can Vet J. 2003 Feb; 44(2):132-6.
13. Welle M, Philipp U, Rufenacht S, Roosje P, Scharfenstein M, Schutz E, Brenig B, Linek M, Mecklenburg L, Grest P, Drogemuller M, Haase B, Leeb T, Drogemuller C: MLPH Genotype--Melanin Phenotype Correlation in Dilute Dogs. J Here'd, 2009

Click the slide to view.

3-1. Haired skin

3-2. Haired skin

Back | VP Home | Contact Us |