Enamel renal syndrome: A novel homozygous FAM20A founder mutation in 5 new Brazilian families

Abstract

Enamel renal syndrome (ERS) is a rare autosomal recessive disorder that still not fully characterized. Here we investigated ERS characteristics in 11 patients from 5 Brazilian families through clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing. The patients' age ranged from 6 to 25 years old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium).Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutations in FAM20A gene, characterized by one base pair deletion in exon 11, resulting in a frameshift replacing a glutamine at codon 483 for a lysine and terminating at position 24 [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], were detected in all patients, strongly suggesting a founder effect. Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Early diagnosis is essential to minimize the deleterious effects related to ERS. Here we report the largest series of patients with ERS in the same population, and describe, for the first time, a founder mutation for FAM20A.

Amelogenesis imperfecta with multiple impacted teeth and altered eruption pathways - A radiographic case report

“…These features have previously been reported in association with FAM20A mutation. 13,46 However to our knowledge this is the first reported case showing altered eruption pathways of impacted teeth in AI.…”

Syndromes with gingival fibromatosis: A systematic review

“…The present SR included 218 individuals affected by syndromes that contained GF in the clinical spectrum, representing 82 case reports (173 individuals) and 2 case series (45 individuals). The studies were published between 1958 (McIndoe & Smith, 1958) and 2019 (Debnath, Couthino, Chatterjee, & Shenoy, 2019; Dourado et al., 2019), and the characteristics of studies are summarized in Table . The geographic distribution of the individuals was as follows: 59 from Asia, 52 from Latin America, 49 from North America, 33 from Europe, 8 from Africa, and 6 from Oceania (Figure ).…”

“…The extent of GF was observed to be generalized in 77 studies, localized in six articles (Chacon‐Camacho, Vázquez, & Zenteno, 2011; Chadwick, Hunter, Hunter, Aldred, & Wilkie, 1994; Giansanti, McKenzie, & Owens, 1973; Goodwin et al., 2014; Hallett, Bankier, Chow, Bateman, & Hall, 1995; Ishita, Sujatha, Pramod, & Ashok, 2016), and not determined in one study (Pachajoa, López‐Quintero, Vanegas, Montoya, & Ramírez‐Montaño, 2018). The degree of severity was also assessed, with 15 studies reporting mild fibromatosis (Abo‐Dalo et al., 2008; Afifi et al., 2015; Ashkenazi, Rafe, Sarnat, & Levin, 2014; Debnath et al., 2019; Dourado et al., 2019; Feitosa et al., 2011; Giansanti et al., 1973; Goodwin et al., 2014; Hartsfield, Bixler, Hazen, Opitz, & Reynolds, 1985; Holzhausen et al., 2003; Landoulsi et al., 2012; Laouina & Zupan, 2017; Mangino et al., 2003; Martelli‐Júnior et al., 2008; O’Connell, Davies, Smallridge, & Vaidyanathan, 2014), 25 studies reporting moderate fibromatosis (Afifi, Abdel‐Hamid, Eid, Mostafa, & Abdel‐Salam, 2016; Bhesania, Arora, & Kapoor, 2015; Castori et al., 2013; Jaouad et al., 2015; Cho et al., 2012; Goldblatt & Singer, 1992; Kaisare, 2007; Kang, Lee, Jeon, Song, & Kim, 2018; Kantaputra et al., 2017; Kissi, Benyahya, & Rifki, 2006; Lee, Im, & Kim, 1993; Lin, Wang, Sun, & Huang, 2010; Martins, Ortega, Hiraoka, Ricardo, & Magalhaes, 2010; Mégarbané et al, 2016; Molano, Blank, Tamayo, & Isaza, 1996; Oikarinen, Salo, Ka, Lahtela, & Altonen, 1990; Paula, Melo, Guerra, Mestrinho, & Acevedo, 2005; Pêgo et al., 2017; Poulter et al., 2015; Prasad, Radharani, Sinha, & Kumar, 2012; Singer, Goldblatt, Hallam, & Winters, 1993; Torres et al., 2018; de la Tranchade, Bonarek, Marteau, Boileau, & Nancy,…”

“…A total of 18 individuals with gingival ectopic calcifications had AI, being present in six individuals with ERS (Bhesania et al, 2015; Debnath et al., 2019; Kantaputra et al., 2017; O’Connell et al., 2014; Pêgo et al., 2017; Torres et al., 2018); five individuals with Raine syndrome (RS; OMIM#259775) (Acevedo et al., 2015); four individuals with GF and dental abnormalities (Martelli‐Júnior et al., 2008); one individual with GF, AI, and tooth eruption defects (Molano et al., 1996); one individual with autosomal recessive rough hypoplastic AI (Ooya et al., 1988); and one individual with rough hypoplastic AI, dental follicular hamartomas, and gingival hyperplasia (Roquebert et al., 2008). In most of these studies, ectopic calcifications were reported in other oral tissues as well, including dental pulps in 35 individuals (Debnath et al., 2019; Dourado et al., 2019; Ashkenazi et al., 2014; Martelli‐Júnior et al., 2008; O’Connell et al., 2014; Kang et al., 2018; Kantaputra et al., 2017; Paula et al., 2005; Pêgo et al., 2017; Wang et al., 2013; Acevedo et al., 2015; Kantaputra et al, Ooya et al., 1988; Roquebert et al., 2008) and dental follicles in 8 individuals (Acevedo et al., 2015; Paula et al., 2005; Roquebert et al., 2008; de la Tranchade et al., 2003) (Figure ).…”

Enamel Renal Syndrome: A Scoping Review Protocol

“…Enamel Renal Syndrome (ERS) (OMIM # 204690) is a rare autosomal recessive disorder characterized by hypoplastic amelogenesis imperfecta (AI), failed tooth eruption, intra-pulpal calci cations, gingival enlargement and nephrocalcinosis (1). in 1972, MacGibbon described a condition presenting with renal dysfunction and enamel hypoplasia in several members of the same family (2).…”