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Multicenter Study
. 2024 May 1;160(5):544-549.
doi: 10.1001/jamadermatol.2024.0065.

Orofacial Anomalies in Kindler Epidermolysis Bullosa

Susanne Krämer  1   2 , Anna Lena Hillebrecht  3 , Yao Wang  1 , Mihail-Alexandru Badea  4 , Jose Ignacio Barrios  5 , Sorina Danescu  6 , Ignacia Fuentes  7   8   9 , Demet Kartal  10 , Alfred Klausegger  11 , Enrique Ponce de León  2 , Reinhard Schilke  12 , Ivelina Yordanova  13 , Agnes Bloch-Zupan  14   15   16   17 , Cristina Has  1
Affiliations
Multicenter Study

Orofacial Anomalies in Kindler Epidermolysis Bullosa

Susanne Krämer et al. JAMA Dermatol. .

Abstract

Importance: Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported.

Objective: To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa.

Design, settings, and participants: This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa.

Main outcomes and measures: The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma.

Results: The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients).

Conclusions and relevance: These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Syndromic Amelogenesis Imperfecta in Kindler Epidermolysis Bullosa
A and B, Hypoplastic pitted syndromic amelogenesis imperfecta with generalized pits in patient 26. C, Generalized pitting in patient 10. D, Localized pits on upper and lower premolars in patient 9.
Figure 2.
Figure 2.. Orofacial Anomalies in Kindler Epidermolysis Bullosa
A, Chronic wound on the lip of patient 12. B, Angular cheilitis in patient 25. C, The same patient 1 year later when oral squamous cell carcinoma was diagnosed. D, Gingival overgrowth. E, Severe limited mouth opening (microstomia) in patient 26.
See this image and copyright information in PMC

References

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