Prepair 1000+

Gene: FERMT1

Green List (high evidence)

Genereviews PMID: 26937547: Kindler syndrome (KS), a rare subtype of inherited epidermolysis bullosa, is characterized by skin fragility and acral blister formation beginning at birth, diffuse cutaneous atrophy, photosensitivity (most prominent during childhood and usually decreasing after adolescence), poikiloderma, diffuse palmoplantar hyperkeratosis, and pseudosyndactyly. Mucosal manifestations are also common and include hemorrhagic mucositis and gingivitis, periodontal disease, premature loss of teeth, and labial leukokeratosis. Other mucosal findings can include ectropion, urethral stenosis, and severe phimosis. Severe long-term complications of KS include periodontitis, mucosal strictures, and aggressive squamous cell carcinomas. Manifestations can range from mild to severe.

The phenotypic spectrum ranges from mild to severe based on age of onset, organs involved, and severity of manifestations. The mild end of the spectrum is characterized by minimal skin involvement (such as that observed in adults with KS), with or without other mild manifestations. Some individuals with mild manifestations are not diagnosed until late in life; for example, two individuals were diagnosed by molecular genetic testing in their 60s and 70s after early-stage cutaneous precancerous lesions and epithelial skin cancer were identified and treated in their 50s [Has et al 2010]. In contrast, the severe end of the spectrum is characterized by such findings as severe mucosal involvement, severe esophageal stenosis, pseudoainhum, anemia, and/or malignancies.

Most FERMT1 variants associated with Kindler syndrome are null variants. It has been proposed that FERMT1 pathogenic missense variants and in-frame deletions are associated with milder disease manifestations and later onset of complications [Maier et al 2016].

Created: 13 Dec 2024, 4:56 a.m. | Last Modified: 13 Dec 2024, 4:56 a.m.

Panel Version: 1.819

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Kindler syndrome MIM#173650

Publications

• 26937547