What is kindler syndrome?
Kindler syndrome is a condition that causes skin fragility and leads to easy blistering, among other symptoms. It belongs to a group of genetic conditions called epidermolysis bullosa.[1] Theresa Kindler, the conditions namesake, described the syndrome in 1954.[3] While it is a rare condition, only affecting 250 people worldwide, the symptoms are quite severe. Some parts of the condition become less severe over time, but many new complications arise over time. It is caused by a gene called FERMT1 which encodes a protein called kindlin-1 which is responsible for several functions within epithelial (skin) cells[1]. Some rare cases result in a type of cancer called squamous cell carcinoma.[4] The exact mechanism behind how this happens in currently unknown.
kindler syndrome symptoms
Patients with Kindler syndrome can experience a wide range of symptoms. The most common symptoms include blistering on the hands and feet, scarring due to the blistering, and development of thin skin all over the body. UV sensitivity is an issue for individuals with this condition. Other symptoms include poikiloderma (skin discoloration with small clusters of blood vessels below the skin), hyperkeratosis (hardening and thickening of skin under the feet or on the palms of the hands), and complications with the moist lining inside several organs. Lining complications can lead to impaired vision, gum disease and tooth loss, difficulty swallowing due to esophagus inflammation, and a variety of health issues from inflammation of the gastrointestinal tract. In addition to the other symptoms, those with Kindler syndrome are at an increased risk for a cancer called squamous cell carcinoma which is a cancer of the epidermis. [1] A case of synchronous bilateral breast cancer has occurred in a woman after giving birth. [3]
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Diagnosis |
Treatment
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Diagnosing a rare condition like Kindler syndrome can be difficult. Currently, genetic testing is used to confirm cases that are suspected based on patient history. [1,2] Patients are diagnosed when they show biallelic FERMT1 variants, immunofluorescence on a skin biopsy of a blister, or positive histological results. Typically, patients show skin abnormalities within the first year of life, but some cases are not diagnosed until much later. This is because there are several inherited skin conditions that cause blistering in young patients. [3]
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There are no established treatments for Kindler syndrome currently. Symptoms can be managed through a variety of methods, such as moisturizers, limiting sun exposure, and basic blister care. A team of specialists, from dermatologists to urologists, can work together to help patients live with symptoms. As a preventative measure, patients should undergo cancer screening regularly due to their increased risk. [1,2] Antioxidants and luteolin (a plant flavenoid) could be used as a topical treatment for the condition eventually because they have been shown to reduce cell death in Kindler Syndrome cells in lab experiments with UV light.[3]
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FERMT1 gene
Mutations in the FERMT1 gene are believed to cause Kindler syndrome. As displayed by the image below, the gene is located on the short arm of chromosome 20 at position 12.3. FERMT1 codes for the protein kindlin-1. This protein is responsible for several critical functions of keratinocytes (epithelial or skin) cells. Kindlin-1 plays a role in cell movement, the cells ability to adhere to the structure beneath them, and cellular growth and division.[1] Mutated kindlin-1 does not allow the bottom layer of the epidermis to adhere to the basement layer below it, leading to many symptoms.[3] Kindler syndrome is inherited in an autosomal recessive manner, meaning individuals only get the condition when they have two recessive alleles, because FERMT1 mutations result in the protein being non-functional. [1]
References
1. Kindler Syndrome. (2020, January 21st). Retrieved February 4th, 2020, from https://ghr.nlm.nih.gov/condition/kindler-syndrome.
2. Kindler Syndrome. (2016, November 30th). Retrieved February 4th, 2020, from https://rarediseases.info.nih.gov/diseases/4391/kindler-syndrome
3. Linfante, A. (2018, August 24th). Kindler Syndrome. Retrieved February 6th, 2020, from https://emedicine.medscape.com/article/1118967-overview
4. Souldi, H. (2018, February). Kindler syndrome complicated by invasive squamous cell carcinoma of the palate. Retrieved February 6th, 2020, from https://www.sciencedirect.com/science/article/pii/S1879729617300972?via%3Dihub
2. Kindler Syndrome. (2016, November 30th). Retrieved February 4th, 2020, from https://rarediseases.info.nih.gov/diseases/4391/kindler-syndrome
3. Linfante, A. (2018, August 24th). Kindler Syndrome. Retrieved February 6th, 2020, from https://emedicine.medscape.com/article/1118967-overview
4. Souldi, H. (2018, February). Kindler syndrome complicated by invasive squamous cell carcinoma of the palate. Retrieved February 6th, 2020, from https://www.sciencedirect.com/science/article/pii/S1879729617300972?via%3Dihub
Header Image: https://www.istockphoto.com/photos/skin-cells?sort=mostpopular&mediatype=photography&phrase=skin%20cells
Symptoms Image 1: http://www.ijpd.in/article.asp?issn=2319-7250;year=2016;volume=17;issue=3;spage=235;epage=238;aulast=Morgaonkar
Symptoms Image 2: https://www.science20.com/scientist/kindler_syndrome
Diagnosis and Treatment Image: https://www.lybrate.com/topic/symptoms-and-treatment-kindler-s-syndrome/a5fb906f6f71bed8bb5bf631a6763990
FERMT1 Gene Image 1: https://ghr.nlm.nih.gov/gene/FERMT1
Symptoms Image 1: http://www.ijpd.in/article.asp?issn=2319-7250;year=2016;volume=17;issue=3;spage=235;epage=238;aulast=Morgaonkar
Symptoms Image 2: https://www.science20.com/scientist/kindler_syndrome
Diagnosis and Treatment Image: https://www.lybrate.com/topic/symptoms-and-treatment-kindler-s-syndrome/a5fb906f6f71bed8bb5bf631a6763990
FERMT1 Gene Image 1: https://ghr.nlm.nih.gov/gene/FERMT1
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison."