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Pathognomonic oral profile of Enamel Renal Syndrome (ERS) caused by recessive FAM20A mutations

Muriel de la Dure-Molla12*, Mickael Quentric13, Paulo Marcio Yamaguti4, Ana-Carolina Acevedo45, Alan J Mighell6, Miikka Vikkula3, Mathilde Huckert11789, Ariane Berdal12 and Agnes Bloch-Zupan10789

Author Affiliations

1 Laboratory of Molecular Oral Pathophysiology, INSERM UMRS 1138, Cordeliers Research Center, Paris, France

2 Center of Rare Malformations of the Face and Oral Cavity (MAFACE), Hôpital Rothschild, Paris, France

3 Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium

4 Oral Care Center for Inherited Disease, University Hospital of Brasilia, University of Brasilia, Brasilia, Brazil

5 Department of Dentistry, Health Sciences School, University of Brasilia, Brasilia, Brazil

6 School of Dentistry, The University of Leeds, Leeds, UK

7 Faculty of Dentistry, University of Strasbourg (UdS), Strasbourg, France

8 Reference Centre for Orodental Manifestations of Rare Diseases, Pôle de Médecine et Chirurgie Bucco-Dentaires, Hôpitaux Universitaires de Strasbourg (HUS), Strasbourg, France

9 Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France

10 Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS UMR 7104 - Inserm U 964, Illkirch, France

11 Laboratoire de Génétique Médicale, UMRS 1112, Faculty of Medicine, UdS, Strasbourg, France

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Orphanet Journal of Rare Diseases 2014, 9:84  doi:10.1186/1750-1172-9-84

Published: 14 June 2014


Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects. Commonly described as an isolated trait, it may be observed concomitantly with other orodental and/or systemic features such as nephrocalcinosis in Enamel Renal Syndrome (ERS, MIM#204690), or gingival hyperplasia in Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS, MIM#614253). Patients affected by ERS/AIGFS present a distinctive orodental phenotype consisting of generalized hypoplastic AI affecting both the primary and permanent dentition, delayed tooth eruption, pulp stones, hyperplastic dental follicles, and gingival hyperplasia with variable severity and calcified nodules. Renal exam reveals a nephrocalcinosis which is asymptomatic in children affected by ERS. FAM20A recessive mutations are responsible for both syndromes. We suggest that AIGFS and ERS are in fact descriptions of the same syndrome, but that the kidney phenotype has not always been investigated fully in AIGFS. The aim of this review is to highlight the distinctive and specific orodental features of patients with recessive mutations in FAM20A. We propose ERS to be the preferred term for all the phenotypes arising from recessive FAM20A mutations. A differential diagnosis has to be made with other forms of AI, isolated or syndromic, where only a subset of the clinical signs may be shared. When ERS is suspected, the patient should be assessed by a dentist, nephrologist and clinical geneticist. Confirmed cases require long-term follow-up. Management of the orodental aspects can be extremely challenging and requires the input of multi-disciplinary specialized dental team, especially when there are multiple unerupted teeth.

Enamel Renal Syndrome (ERS); Amelogenesis Imperfecta and Gingival Fibromatosis syndrome (AIFGS); Enamel Dysplasia with Hamartomatous atypical Follicular Hyperplasia Syndrome (EDHFH); Amelogenesis Imperfecta; Enamel defect; Delayed tooth eruption; Intra-pulpal calcification; Gingival hyperplasia; FAM20A