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Orphanet J Rare Dis. 2019 Jul 24;14(1):183. doi: 10.1186/s13023-019-1158-6.

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

Author information

1
Department of Bioengineering, Universidad Carlos III de Madrid, Leganés, Madrid, Spain.
2
Hospital Fundación Jiménez Díaz e Instituto de Investigación FJD, Madrid, Spain.
3
Epithelial Biomedicine Division, CIEMAT, Madrid, Spain.
4
Centre for Biomedical Network Research on Rare Diseases (CIBERER), U714, Madrid, Spain.
5
Department of Bioengineering, Universidad Carlos III de Madrid, Leganés, Madrid, Spain. cconti@ing.uc3m.es.
6
Hospital Fundación Jiménez Díaz e Instituto de Investigación FJD, Madrid, Spain. cconti@ing.uc3m.es.
7
Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Rome, Italy.
8
Genetic and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, 00165, Rome, Italy.
9
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
10
Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
11
Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
12
Department of Dermatology, University Hospital Basel, Basel, Switzerland.
13
Pediatric Dermatology, Department of Physiopathology and Transplantation, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, University of Milan, Milan, Italy.
14
Department of Dermatology and Venerology, Medical University Pleven, Pleven, Bulgaria.
15
Department of Dermatology, Angers University Hospital, Angers, France.
16
Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.

Abstract

BACKGROUND:

Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients.

RESULTS:

The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease.

CONCLUSIONS:

This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.

KEYWORDS:

Bullous disease; Kindler syndrome; Prevalence; SCC; Skin cancer

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