Ehlers-Danlos syndrome (EDS) is a genetic disorder characterized by defective collagen synthesis in humans (1,6). It leads to fragility and hyperextensibility of the connective tissues supporting the skin, bones, blood vessels, and various other organs and tissues. The International EDS Consortium proposed a revised EDS classification system in humans, which recognizes 13 different subtypes such as classical, cardiac-valvular, vascular, hypermobile, and arthrochalasia. The major clinical criteria of classical EDS are skin hyperextensibility and generalized joint hypermobility, whereas the minor criteria are easy bruising, skin fragility, and complications of joint hypermobility, such as luxation and subluxation. In humans, EDS is inherited in an autosomal-recessive manner and is associated with mutations in several genes, such COL5A1, COL1A1, COL1A2, and COL3A1 (6). However, there is a lack of research on the EDS-related genes in dogs and cats. Consequently, there is no genetic screening test to diagnose EDS in animals. Thus, it is diagnosed using the skin extensibility index and histopathological examination of the collagen structure in animals. The skin extensibility index is a measure of the skin’s elasticity or ability to stretch and is used to diagnose connective tissue disorders. It is calculated by dividing the vertical height of a skin fold by the body length from the tail base to the occipital crest and multiplying the result by 100 (%). The skin extensibility index in normal cat ranges from 11 ± 2% to less than 19%. An index greater than 14.5% in dogs, and 19% in cats, is a diagnostic indication of EDS (3,10).

EDS is a rare condition in dogs and cats and has been mainly reported in the Birman and Himalayan breeds (2-4,8). This study describes a rare case of EDS in a Korean shorthair cat.

A 1-year-old castrated male Korean shorthair cat presented with recurrent instances of multiple small skin tears and bruises scattered across the entire trunk region. The owner rescued a street kitten and the cat underwent three suture surgeries due to skin tears until the age of 1 year. The cat’s skin was hyperextensible and easily torn with even gentle touch. The cat’s vertical height of a dorsal skin fold was 8 cm and the body length from the tail base to the occipital crest was 32 cm. The skin extensibility index of the cat was found to be 25% greater than that of the normal cat range (from 11 ± 2% to less than 19%), a diagnostic indication of EDS.

The cat exhibited no signs of pruritus or inflammation. Skin cytology, skin scraping, and trichogram results were unremarkable. Complete blood cell count, serum biochemistry, urinalysis, urinary cortisol-to-creatinine ratio, radiography, and ultrasonography results ruled out any other underlying diseases (Table 1). Radiography revealed a hip joint subluxation and arthritis (Fig. 1). Subsequently, skin suture surgery and biopsy of the lacerated skin was performed (Fig. 2).

Table 1 . Complete blood count, serum chemistry, and urinalysis of the cat.

Index	Result	Reference range	Unit
RBC	10.71	6.54-12.2	106/μL
HCT	51.1	30.3-52.3	%
HGB	16.2	9.8-16.2	g/dL
MCV	47.7	35.9-53.1	fL
MCH	15.1	11.8-17.3	pg
MCHC	31.7	28.1-35.8	g/dL
RETIC	19.3	3-50	103/μL
WBC	9.51	2.87-17.02	103/μL
WBC-NEU	3.91	1.48-10.29	103/μL
WBC-LYM	4.75	0.92-6.88	103/μL
WBC-MONO	0.32	0.05-0.67	103/μL
PLT	271	151-600	103/μL
BUN	21.9	16.0-36.0	mg/dL
CREA	1.04	0.8-2.4	mg/dL
ALP	49	9-109	U/L
GPT	84	12-130	U/L
GLU	140	74-152	mg/dL
ALB	4.1	2.2-4.1	g/dL
TBIL	0.24	0-1.0	mg/dL
GLOB	3.6	2.5-4.5	g/dL
TP	7.7	5.8-9.1	g/dL
Urine Glucose	0	0-50	mg/dL
Urine Ketone	0	0	mg/dL
Urine Protein	0	0-100	mg/dL
Urine Cortisol : Creatinine ratio	5.77	<34	%

RBC, red blood cell; HCT, hematocrit; HGB, hemoglobin; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RETIC, reticulocyte; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; MONO, monocyte; PLT, platelet; BUN, blood urea nitrogen; Cre, creatinine; ALP, alkaline phosphatase; GPT, glutamic pyruvic transaminase; GLU, glucose; ALB, albumin; TBIL, total bilirubin; GLOB, globulin; TP, total protein..

Figure 1. Ventrodorsal hip joint radiographs of the cat. Hip joint subluxation and arthritis was observed.

Figure 2. Excessively stretched skin of the Korean shorthair cat with Ehlers-Danlos syndrome. Extent of skin stretching measured using a scaler. Skin suture surgery and biopsy of the lacerated skin was performed.

Skin histopathology confirmed EDS in the cat. In the dermis adjacent to the lesions, the collagen fibers were irregular in size and width, with a slightly thinner epidermis and increased interfibrillar spaces containing low numbers of scattered well-differentiated fibroblasts and mast cells. Periodic acid-Schiff stain was negative (Fig. 3).

Figure 3. Histopathology of the skin lesion. The collagen fibers are irregular in size and width, with increased interfibrillar spaces containing low numbers of scattered well-differentiated fibroblasts and mast cells. (A) Haired skin with dysplastic dermal collagen bundles. H & E, ×50. (B) Collagen fibers are irregular in size and width, with increased interfibrillar spaces. H & E, ×100. (C) Dysplastic dermal collagen bundles with increased interfibrillar spaces. H & E, ×200. (D) Collagen fiber (black arrowheads), fibroblast (blue arrowheads), mast cell (red arrowheads), H & E, ×400.

Oral medications, including 10 mg/kg amoxicillin and 1 mg/kg famotidine twice daily, were administered for 3 weeks after surgery. After diagnosis of EDS, the owner trained to protect the cat from high-risk environments. The cat was kept clothed to protect it from sharp furniture and its claws were cut short to prevent self-trauma. Contact with cohabitating cats was minimized. The cat remained healthy, without needing additional suture surgery, 18 months after the diagnosis of EDS.

In humans, EDS is diagnosed by the presence of COL5A1, COL1A1, COL1A2, and COL3A1 gene defects. Other than skin extensibility index and biopsy, methods for diagnosing gene defects of EDS have not yet been identified in veterinary medicine. However, genetic analysis of five cats diagnosed EDS by histological examination was reported that there is COL5A1 gene defect (5,9). Genetic analysis of collagen synthesis could be useful to confirm the diagnosis of EDS in the cat reported in this study. Due to the local movement of the cat’s owner, it is difficult to collect oral epithelial cells, which is a limitation to performing additional genetic analysis in this study. Based on the result of histological examination, it is estimated that there are gene defects of collagen synthesis when genetic analysis is performed on this cat.

The skin extensibility index in normal cat ranges from 11 ± 2% to less than 19%. An index greater than 14.5% in dogs and 19% in cats is a diagnostic indication of EDS. This study confirms that a >19% skin extensibility index can effectively indicate EDS, and until a genetic testing technique is established for animals, EDS can be diagnosed through biopsy in cats with increased skin extensibility.

EDS is an autosomal-recessive disease in humans. In animals, EDS has mainly been reported in purebred cats like the Birman and Himalayan breeds. In this case, we confirmed that EDS can occur in mixed breed Korean shorthair cat. An EDS case in a domestic Korean shorthair cat was first reported in 2016 (7). The cat in this case also belongs to a Korean shorthair mixed breed, and this is the second report of EDS in a Korean shorthair cat. Compared to the cat in the EDS 2016 case report, this cat had arthritis and hip joint subluxation, and was able to approach the detailed classification of EDS.

In humans, EDS is classified into 13 subtypes, such as classical, cardiac-valvular, vascular, hypermobile, and arthrochalasia. The major clinical criteria of classical EDS are skin hyperextensibility and generalized joint hypermobility, whereas the minor criteria are easy bruising, skin fragility, and complications of joint hypermobility, such as luxation and subluxation (6). In the present case, the cat had skin hyperextensibility and multiple bruising. Although young, the cat presented with hip joint subluxation and arthritis. Therefore, the symptoms of this cat were most similar to those of the classical EDS subtype in humans.

Currently, there is no cure for EDS. It is recommended to neuter affected animals to prevent breeding. In addition, it is crucial to inform the owners that the disease is incurable and that the animal will require lifelong care. A risk assessment should be conducted by checking houses for furniture with sharp edges; these should be either removed or covered with protective equipment. Preventive measures against skin disorders such as allergic dermatitis that can prompt a pruritic response should also be implemented. Nails of affected cats should be kept short and blunt. Affected cats should be kept clothed and interactions with other cats in the household should be minimized. With care, a cat with EDS can still have a normal lifespan.

EDS, an autosomal-recessive disease in humans, is mainly reported in purebred cats. To the best of our knowledge, this is a rare case report of feline EDS in a Korean shorthair mixed breed cat, and the first study to classify the subtype of EDS as classical in a cat.

This research was supported by ”Regional Innovation Strategy (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2023RIS-009).

The authors have no conflicting interests.