Orofacial Anomalies in Kindler Epidermolysis Bullosa

Susanne Krämer; Anna Lena Hillebrecht; Yao Wang; Mihail-Alexandru Badea; Jose Ignacio Barrios; Sorina Danescu; Ignacia Fuentes; Demet Kartal; Alfred Klausegger; Enrique Ponce de León; Reinhard Schilke; Ivelina Yordanova; Agnes Bloch-Zupan; Cristina Has

doi:10.1001/jamadermatol.2024.0065

. 2024 Mar 20;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

¹Department of Dermatology, Medical Faculty and Medical Center, University of Freiburg, Freiburg, Germany

²Special Care Dentistry Unit, Facultad de Odontologia, Universidad de Chile, Santiago, Chile

³Department of Prosthetic Dentistry, Centre for Dental Medicine, Medical Centre, University of Freiburg, Freiburg, Germany

⁴Dermatology Department, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Targu-Mures, Targu-Mures, Romania

⁵Maxillo Facial Department, Clinica Alemana, Santiago, Chile

⁶Department of Dermatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

⁷Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

⁸DEBRA Chile, Santiago, Chile

⁹Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile

¹⁰Faculty of Medicine, Department of Dermatology and Venereology, Erciyes University, Kayseri, Turkey

¹¹EB House Austria, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria

¹²Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany

¹³Department of Dermatology and Venerology, Medical University Pleven, Pleven, Bulgaria

¹⁴Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France

¹⁵Université de Strasbourg, Institut d’études Avancées, Strasbourg, France

¹⁶Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-dentaires, Hôpital Civil, Centre de Référence des Maladies Rares Orales et Dentaires, O-Rares, Filière Santé Maladies rares TETE COU, European Reference Network ERN CRANIO, Strasbourg, France

¹⁷Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U1258, CNRS-UMR7104, Illkirch, France

Accepted for Publication: January 11, 2024.

Published Online: March 20, 2024. doi:10.1001/jamadermatol.2024.0065

^✉

Corresponding Author: Susanne Krämer, DDS, MSc, Special Care Dentistry Unit, Facultad de Odontologia, Universidad de Chile, Olivos 943, Independencia, Santiago 8380544, Chile (skramer@odontologia.uchile.cl).

Author Contributions: Drs Krämer and Has had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Krämer, Hillebrecht, Barrios, Yordanova, Has.

Acquisition, analysis, or interpretation of data: Krämer, Wang, Badea, Danescu, Fuentes, Kartal, Klausegger, Ponce de Leon, Schilke, Yordanova, Bloch-Zupan, Has.

Drafting of the manuscript: Krämer, Hillebrecht, Schilke, Yordanova, Bloch-Zupan, Has.

Critical review of the manuscript for important intellectual content: Krämer, Wang, Badea, Barrios, Danescu, Fuentes, Kartal, Klausegger, Ponce de Leon, Schilke, Bloch-Zupan.

Statistical analysis: Krämer, Wang.

Administrative, technical, or material support: Krämer, Hillebrecht, Wang, Barrios, Fuentes, Ponce de Leon, Schilke, Yordanova, Bloch-Zupan, Has.

Supervision: Badea, Danescu, Has.

Conflict of Interest Disclosures: None reported.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We thank DEBRA International, DEBRA Without Borders, DEBRA Germany, DEBRA Austria, and DEBRA Chile for the continuous support to those affected with epidermolysis bullosa worldwide. We thank the patients (except patient 23) for granting permission to publish this information.

^✉

Corresponding author.

PMCID: PMC10955352 PMID: 38506824

Key Points

Question

Is hypoplastic pitted amelogenesis imperfecta a feature of Kindler epidermolysis bullosa?

Findings

In this longitudinal cohort study, deep phenotyping of orofacial features identified enamel structure abnormalities in all 11 patients for whom data were available.

Meaning

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

This cohort study examines whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa, a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1.

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.

Introduction

Epidermolysis bullosa (EB) is a group of genetic disorders characterized by skin and mucosal blistering within the basement membrane zone. Kindler epidermolysis bullosa (KEB) is the rarest EB type and is associated with biallelic pathogenic variants in FERMT1, which encodes kindlin-1, an intracellular protein of focal adhesions. The main role of kindlins is to increase integrin affinity for ligands through binding of β-integrin tails.¹ Kindlin-mediated integrin activation and integrin-ligand binding promote cell adhesion, spreading, and migration; assembly of the extracellular matrix; and cell survival, proliferation, and differentiation.² Lack of integrin activation in the gingiva is associated with severe early-onset periodontitis in patients with KEB.³ Here, we describe orofacial features in a cohort of patients with KEB, including for the first time amelogenesis imperfecta as a manifestation of FERMT1 pathogenic variants.

Methods

This longitudinal cohort study was performed at the EB Centre, University of Freiburg, Freiburg, Germany (2003-2023), and the Special Care Dentistry Clinic, University of Chile, Santiago, Chile, in association with DEBRA Chile (2005-2023). A retrospective analysis of medical records was performed by 3 calibrated clinicians (S.K., A.L.H., and Y.W.; interexaminer and intraexaminer κ values ranged from 0.9 to 1.0). Discrepancies were discussed during a consensus meeting. Ethical approval was obtained from the University of Freiburg and the University of Chile. Patients gave written consent for publication of their clinical pictures and oral consent for clinical assessment. The report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.⁴ We used Excel software version 2021 (Microsoft) to manage the data.

Results

Generalized pitted hypoplastic amelogenesis imperfecta was first diagnosed in patient 26 in his thirties (Table and Figure 1). Because reports of FERMT1-associated amelogenesis imperfecta were lacking,⁵ we proceeded in validating this finding.

Table. Orofacial Features in Patients With Kindler Epidermolysis Bullosa^a.

Patient No.	Age at examination, y		Sex	FERMT1 pathogenic variants c.DNA	Kindlin-1 protein	Pitted enamel hypoplasia	Caries/tooth loss	Intraoral erosions/ulcers	Chronic lip ulcers	Cheilitis	Angular cheilitis	Oral squamous cell carcinoma	Gingivitis or periodontal disease	Gingival hyperplasia (overgrowth)	Microstomia	Vestibular obliteration
Patient No.	First	Last	Sex	FERMT1 pathogenic variants c.DNA	Kindlin-1 protein	Pitted enamel hypoplasia	Caries/tooth loss	Intraoral erosions/ulcers	Chronic lip ulcers	Cheilitis	Angular cheilitis	Oral squamous cell carcinoma	Gingivitis or periodontal disease	Gingival hyperplasia (overgrowth)	Microstomia	Vestibular obliteration
1	<1	1-5	Male	676dupC	Q226Pfs*16	NA	NA	Absent	Absent	Absent	Absent	Absent	Absent	Absent	Absent	NA
2	1-5	1-5	Male	676delC;IVS9 + 740G>A	Q226Sfs*25;SS	NA	NA^b	Absent	Absent	Absent	Absent	Absent	Absent	Absent	Absent	NA
3	1-5	1-5	Male	1140-2A>T	SS	NA	NA	Absent	Absent	Absent	Absent	Absent	Present	Absent	Absent	Absent
4	6-12	6-12	Female	1140-2A>T	SS	NA	Present	Absent	Absent	Absent	Absent	Absent	Present	Present	Absent	Absent
5	6-12	6-12	Male	676dupC;877T>G	Q226Pfs*16;Y293D	Present	NA	NA	NA	Absent	Present	Absent	Present	NA	NA	NA
6	6-12	6-12	Male	190G>T	E64*	NA	NA	NA	NA	Absent	Present	Absent	Absent	Absent	NA	NA
7	6-12	6-12	Male	907G>T	E303*	NA	NA	NA	NA	Present	Absent	Absent	NA	NA	NA	NA
8	1-5	6-12	Male	IVS9 + 740G>A	SS	NA	Present	NA	NA	Present	Absent	Absent	Present	Present	NA	NA
9	1-5	13-19	Female	385 + 2T>C	SS	Present	Absent	Present^c	Absent	Present	Present	Absent	Present	Present	Absent	Absent
10	1-5	13-19	Female	676dupC	Q226Pfs*16	Present	Present	NA	Absent	Absent	Present	Absent	Present	Absent	Absent	Present
11	1-5	13-19	Male	IVS13_15del	Large deletion	Present	Present	Present	Present	Present	Present	Absent	Present	Present	Present	Present
12	6-12	13-19	Male	676dupC;1677G>A	Q226Pfs16;W559	NA	NA	Present	Present	Present	Present	Absent	Present	Absent	Present	NA
13	6-12	20s	Male	IVS13_15del	Large deletion	Present	Present	Present	Absent	Present	Present	Absent	Present	Present	Present	Absent
14	20s	20s^d	Female	676dupC	Q226Pfs*16	NA	All teeth extracted at age 13 y	Absent	NA	Present	Present	Absent	NA	Present	Present	Present
15	13-19	20s^d	Female	IVS9 + 740G>A; IVS2_5del	SS; Large deletion	Present	Present	Present	NA	NA	NA	Absent	Present	Present	Absent	Present
16	13-19	20s	Male	910G>T	E304*	Present	NA	NA	NA	Present	Present	Absent	Present	NA	NA	NA
17	20s	20s	Male	1729delA	S577Afs*14	NA	All incisors crowned at age 22y	NA	NA	Present	Present	Absent	Present	NA	Absent	NA
18	13-19	20s	Male	1209C>G	Y403*	NA	Present	NA	Present	Present	Absent	Absent	NA	NA	NA	NA
19	20s	20s	Male	170C>A	S57*	NA	NA	NA	NA	Present	Present	Absent	Present	NA	Present	NA
20	20s	20s	Female	IVS9_11del	Large deletion	NA	NA	Present	NA	Present	NA	Absent	Present	NA	Present	NA
21	13-19	20s	Female	IVS9 + 740G>A	SS	Present	NA	Present	NA	NA	Present	Absent	Present	Present	Absent	Absent
22	20s	20s	Male	1718 + 1G>A	SS	Present	NA	Present	Absent	Present	Present	Absent	Present	Absent	Absent	Absent
23	20s	20s	Female	676dupC	Q226Pfs*16	NA	All teeth crowned in mid 20s	Present	Absent	Present	Present	Absent	Present	Present	Present	Present
24	20s	20s	Female	IVS9 + 740G>A	SS	NA	NA	NA	NA	Absent	Present	Absent	NA	NA	NA	NA
25	13-19	30s^d	Male	456dupA	D153Rfs*3	NA	All teeth crowned at age 27 y	Present	Absent	Present	Present	At age ≥30 y	Present	Present	Present	NA
26	30s	30s	Male	IVS6_9del	Large deletion	Present	Present	Present	NA	Present	Present	Absent	Present	Absent	Present	Present
27	30s	30s	Female	IVS9 + 740G>A	SS	NA	All teeth extracted at age 28 y	Absent	NA	Absent	Present	Absent	Present	Present	Present	Present
28	30s	40s	Female	676dupC	Q226Pfs*16	NA	Present	Present	NA	Present	NA	Absent	Present	Present	NA	NA
29	30s	40s^d	Male	910G>T	E304*	NA	All teeth crowned at age 42 y	Present	Absent	Present	Present	Absent	Present	Present	Absent	NA
30	20s	50s	Female	IVS13_15del	Large deletion	Present	Present	Present	Present	Absent	Absent	Absent	Present	Present	Present	Absent
31	30s	50s	Male	IVS13_15del	Large deletion	NA	All teeth extracted at age 45 y	Present	Present	Present	Present	Absent	Present	Present	Present	Absent
32	50s	60s^d	Female	IVS13_15del	Large deletion	NA	Present	Present	Absent	Present	Present	At age ≥53 y	Present	Present	NA	Present
33	60s	60s	Male	328C>T	R110*	NA	NA	NA	Absent	Present	Present	Absent	Present	Present	Present	NA
34	60s	60s	Female	1761T>A	R587*	NA	NA	NA	NA	Absent	Present	Absent	NA	NA	NA	NA
35	60s	60s	Male	IVS9 + 740G>A	SS	NA	Present	NA	NA	Present	Present	Absent	NA	NA	Present	NA
36	70s	70s	Female	328C>T	R110*	NA	NA	NA	NA	Absent	Absent	Absent	Present	Absent	NA	NA

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Abbreviations: IVS, intron; NA, not available; SS, splice site variant.

^{^a}

If 1 variant indicated, then it is homozygous.

^{^b}

Refers to dyspigmentation of teeth.

^{^c}

Refers to recurrent mucocele.

^{^d}

Patient is deceased.

Figure 1. — 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.

Validation of Amelogenesis Imperfecta in KEB

Clinical records of 65 patients with KEB were reviewed. Information on orofacial features was available for 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]). Follow-up ranged from 1 to 24 years.

Clinical records of 11 patients included information on enamel structure. All had pitted enamel anomalies, but the severity of the pits was variable; for example, patients 10, 21, 22, and 26 showed generalized pitted enamel of most teeth (Figure 1A-1C), whereas patient 9 presented with localized pits on premolars only (Figure 1D). Among the patients whose enamel could not be analyzed, 3 had all teeth crowned in their twenties, suggesting possible generalized enamel defects, and 2 patients had all teeth extracted in their second or third decade of life, indicating severe periodontal disease (Table).

Additional Orofacial Anomalies and Their Management

The most common orofacial feature was periodontal disease, found in 75% of the cohort (27 of 36 patients), including 90% (27 of 30 patients) of those examined, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), and cheilitis (22 of 34 patients [65%]) (Table). Two patients presented with chronic lip ulcers in their second decade of life (Figure 2A). On histopathologic examination, patient 12’s lesion was diagnosed as granuloma pyogenicum, whereas patient 18’s lesion was diagnosed as plasma cell cheilitis. Both lesions healed under topical clobetasol propionate, 0.05% twice daily (eFigure 1 in Supplement 1).

Figure 2. — 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.

Cheilitis angularis was a highly prevalent, but probably neglected, feature. Patient 25 presented with chronic angular cheilitis with Candida albicans and Staphylococcus aureus that did not heal over 19 years of follow-up. In his thirties, a verrucous squamous cell carcinoma (SCC) was diagnosed at that site (Figure 2B and 2C; eFigure 2 in Supplement 1). Despite surgery and anti–epidermal growth factor receptor therapy, the tumor relapsed and extended to the oral cavity, tongue, tonsilla, and lymph nodes, causing the patient’s death 4.5 years later. Patient 32 also developed SCC with lethal outcome at a site of chronic lesions on the lower lip.⁶

Gingivitis and periodontal disease represented a major clinical issue, even at young ages. Gingival overgrowth was diagnosed in 17 of the 26 patients (65%) assessed. It was present as early as the age of 3 years (patient 8). Histopathologic analysis of excised lesions of patient 23 showed chronic inflammation, granulation tissue, ulceration, and fibrosis with a plasma cell–rich inflammation. In patients 9, 23, 25, and 27, gingival overgrowth required surgical removal, with high relapse rate.

Scarring complications of the oral cavity were also common. Microstomia with variable severity was diagnosed in 14 of 25 patients assessed (56%). Patient 26 had a maximal mouth opening of 6 mm in his thirties (Figure 2E and eFigure 3 in Supplement 1). This limited his oral intake, affecting his general condition. After 2 oral maxillofacial surgical procedures, his mouth opening improved, but scarring relapsed 1 year later, despite mouth stretching exercises (eFigure 3D-3H in the Supplement 1). Obliteration of the oral vestibule was present in 8 of 16 assessed patients (50%), causing functional problems. Patients 15 and 26 required oral surgery to deepen the oral vestibule.

Discussion

The findings of this cohort study underscore the extent and severity of oral manifestations in KEB and the need for early and sustained dental care.⁷ We found enamel defects in the form of pitted amelogenesis imperfecta in all patients for whom information was available. Amelogenesis imperfecta is a heterogeneous group of rare genetic diseases presenting with developmental enamel defects (eg, hypoplasia, hypomaturation, and hypomineralization) that can exist in isolation or as part of a syndrome.⁵ Amelogenesis imperfecta can be associated with tooth hypersensitivity, tooth eruption disturbances, crown resorption, and posteruptive breakdown, as well as periodontal conditions such as gingival hyperplasia and periodontitis.⁸ Early diagnosis is important to establish interceptive strategies.⁷

Pathogenic variants in at least 100 genes have been reported to cause amelogenesis imperfecta.⁵ The genes encode proteins with a role in amelogenesis, acting as enamel matrix proteins or as proteases that degrade them, cell adhesion molecules, or regulators of calcium homeostasis.⁵ Pitted and generalized hypoplastic amelogenesis imperfecta has been associated with junctional EB caused by variants in the genes encoding laminin 332, α6β4 integrin, and type XVII collagen. Enamel abnormalities have been explained by the role of these proteins in cell adhesion within the inner dental epithelium, whose cells are giving rise after terminal differentiation to postmitotic highly specialized ameloblasts, producing and maturing dental enamel.⁷

Kindlin-1 is expressed during tooth development at the E14.5 cap stage both in molars and incisors before ameloblast differentiation.^9,10 FERMT1 is expressed in mouse and fish dental epithelium at placode, bud, and/or cap stages,¹⁰ and also in differentiated secretory ameloblasts.¹¹ As in the case of junctional EB, the absence of kindlin-1 may weaken the anchorage of secretory ameloblasts to the underlying enamel matrix.¹² Enamel hypoplasia was once reported in siblings with KEB, but was considered as an independent item.¹³

Periodontal disease, the main concern in KEB owing to its associated bone and tooth loss,⁷ was found in most of our patients. Signs of generalized gingival inflammation were observed as early as the age of 2 years, and severe periodontal disease resulted in complete loss of teeth as early as the age of 13 years. In contrast, patient 9, who performed dental follow-ups every 6 months, had marginal gingivitis and inflammation of some interdental papilla; however, periodontal probing was uneventful, and radiography revealed no alveolar bone disease at the age of 15 years.

In patients with KEB, oral SCC with poor prognosis may occur at a young age at sites of chronic inflammation. A pathogenic chain including mucosal fragility, tissue damage, inflammation, and bacterial colonization may build the ground for carcinogenesis.¹⁴ DNA repair defects associated with nuclear functions of kindlin-1 and oxidative stress may contribute to early accumulation of oncogenic mutations.¹⁵ Activation of fibroblasts and increased activity of transforming growth factor–β and interleukin-6 represent mechanisms that generate a cancer-prone environment in KEB.¹

Limitations

This study has limitations that should be mentioned. In particular, the number of patients is low. In addition, this is a retrospective analysis.

Conclusions

The findings of this cohort study suggest that hypoplastic pitted amelogenesis imperfecta is a feature associated with KEB with pathogenic FERMT1 variants and underscore the extent and severity of oral manifestations in KEB. In patients with KEB, oral care is mandatory.

Supplement 1.

eFigure 1. Plasma Cell Cheilitis in Kindler Epidermolysis Bullosa

eFigure 2. Angular Cheilitis and Squamous Cell Carcinoma in Kindler Epidermolysis Bullosa

eFigure 3. Microstomia in Kindler Epidermolysis Bullosa

jamadermatol-e240065-s001.pdf^{(446.9KB, pdf)}

Supplement 2.

Data Sharing Statement

jamadermatol-e240065-s002.pdf^{(15.1KB, pdf)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eFigure 1. Plasma Cell Cheilitis in Kindler Epidermolysis Bullosa

eFigure 2. Angular Cheilitis and Squamous Cell Carcinoma in Kindler Epidermolysis Bullosa

eFigure 3. Microstomia in Kindler Epidermolysis Bullosa

jamadermatol-e240065-s001.pdf^{(446.9KB, pdf)}

Supplement 2.

Data Sharing Statement

jamadermatol-e240065-s002.pdf^{(15.1KB, pdf)}

[dbr240002r1] 1.Rognoni E, Widmaier M, Jakobson M, et al. Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation. Nat Med. 2014;20(4):350-359. doi: 10.1038/nm.3490 [DOI] [PMC free article] [PubMed] [Google Scholar]

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PERMALINK

Orofacial Anomalies in Kindler Epidermolysis Bullosa

Susanne Krämer, DDS, MSc

Anna Lena Hillebrecht, DDS

Yao Wang, MSc

Mihail-Alexandru Badea, PhD

Jose Ignacio Barrios, DDS

Sorina Danescu, MD

Ignacia Fuentes, PhD

Demet Kartal, MD

Alfred Klausegger, MSc

Enrique Ponce de León, DDS

Reinhard Schilke, DDS

Ivelina Yordanova, PhD

Agnes Bloch-Zupan, PhD

Cristina Has, MD

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Settings, and Participants

Main Outcomes and Measures

Results

Conclusions and Relevance

Introduction

Methods

Results

Table. Orofacial Features in Patients With Kindler Epidermolysis Bullosaa.

Figure 1. Syndromic Amelogenesis Imperfecta in Kindler Epidermolysis Bullosa.

Validation of Amelogenesis Imperfecta in KEB

Additional Orofacial Anomalies and Their Management

Figure 2. Orofacial Anomalies in Kindler Epidermolysis Bullosa.

Discussion

Limitations

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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Links to NCBI Databases

Table. Orofacial Features in Patients With Kindler Epidermolysis Bullosa^a.