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Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

Amelogenesis imperfecta is characterized by inherited defects in the enamel that can be qualitative or quantita tive. The primary dentition, permanent dentition, or both can be affected by this disorder. It may be associated with morphological or biochemical changes elsewhere in the body. 1 The kidneys are the most commonly affected organ, and may present with disorders such as nephrocalcinosis, nephrolithiasis, and other functional abnormalities. 2 The first case was reported by MacGibbon in 1972; 3 multiple cases have been subsequently diagnosed and the condition has been referred to as enamel renal syndrome, amelogen esis imperfecta and nephrocalcinosis, amelogenesis im perfecta and gingival fibromatosis syndrome, or enamel renal gingival syndrome. 4,5 According to a recent review article, only 16 cases have been reported with the com plete oral, dental, and renal phenotype that is associated with enamel renal syndrome. 4 Although the prevalence of amelogenesis imperfecta is known, the prevalence of ena mel renal syndrome has not been assessed, with the ex ception of one study that emphasized its rarity. 6 Affected patients generally suffer from functional and aesthetic pro blems, leading to an inferior quality of life. 7 The severity of the associated renal disorders has been described as ranging from no complications to chronic renal failure. 8,9 Case Report A 21yearold male patient presented with a chief com plaint of small upper and lower permanent teeth. Accord ing to the history reported by the patient, the size of his teeth never changed with age. No contributing family or medical history was identified. The patient did not report any abnormal oral habits. The findings of his general phy sical examination were normal.
An intraoral soft tissue examination showed the pres ence of brown pigmented gingiva with a normal contour (Fig. 1A). A hard tissue examination revealed retained de ciduous teeth and permanent teeth with atypical findings, as well as multiple decayed teeth (Figs. 1AE). Many of the permanent teeth were missing, and the erupted teeth were widely spaced, with a yellowish brown discoloration (Fig. 1A). The enamel layer was absent clinically and posteruption wearing of the teeth was evident ( The panoramic radiography and conebeam computed tomography (CBCT) images revealed multiple findings. All of the teeth were affected, especially the posterior teeth ( Fig. 2A). Multiple calcification nodules were seen in the pulp chambers of the primary and permanent teeth; these nodules were needleshaped in the incisors and round in the posterior teeth ( Figs. 2A and B). The differ ential radiodensity expected between the dentine and the enamel was absent (Fig. 2B). Pericoronal radiolucencies delineated by sclerotic margins around nonerupted teeth were significant ( Figs. 2A and B). The impacted teeth pre sented with complete root formation, exhibiting dilacera tions and curvature ( Fig. 2A). The dental follicles around the unerupted teeth appeared to be hyperplastic (Figs. 2A and B). Extensive crown resorption with partial replace ment of the resorbed dentin by globular calcified struc tures was observed (Fig. 2C).
The impacted permanent canines, second molars, and third molars were observed to have fully formed roots ( Fig.   2A). An accessory mental foramen was seen on the right side of the mandible and extensive bone loss was observ ed around the mesiobuccal root of the left maxillary first molar in the volumerendered CBCT images (Figs. 2D and E). A provisional diagnosis of amelogenesis imper fecta was made based on the clinical and radiographic findings. The histopathological examination of an extract ed deciduous canine using light microscopy confirmed the absence of enamel and the absence of scalloping of the dentinoenamel junction. (Fig. 3A). Hence, based on the Witkop classification, 10 the final diagnosis was the enamel agenesis (type 1G) subtype of hypoplastictype amelogen esis imperfecta, which is an autosomal recessive disorder. The histopathological analysis of specimens obtained during treatment also confirmed the presence of calcified pulpal tissue (Fig. 3B) and dense collagen bundles with abundant vasculature in the gingival tissue (Fig. 3C).
As this type of amelogenesis imperfecta can be associ ated with other organ and metabolic abnormalities, further investigations were carried out. An ultrasound examina tion of his kidneys demonstrated multiple hyperechoic foci in the medulla of both the kidneys, suggesting bilate ral nephrolithiasis (Figs. 4A and B). A 24hour urine spec trophotometric analysis revealed very low citrate levels (18.9 mg/24 hours; reference range, 116924 mg/24 hours). Other biochemical and haematological findings were nor mal (alkaline phosphatase, 128 U/L; urea, 12.84 mg/dL, blood urea nitrogen, 6 mg/dL; creatinine, 1.33 mg/dL,

discussion
A general dental practitioner may come across many cases of amelogenesis imperfecta; however, it is difficult to ensure an accurate diagnosis due to its complex clas sification and the likely absence of relevant data from family members. 11 The clinical features of amelogenesis imperfecta vary depending on the type. 1113 In the hypo plastic type of amelogenesis imperfect, the teeth exhibit a chalky white to dark brown colour, the occlusal surfaces and incisal edges are generally abraded, and occasionally, the complete loss of the enamel is observed. In the hy pocalcified form of amelogenesis imperfecta, the enamel exhibits a cheesy consistency and can be easily removed with a sharp explorer. The hypomaturative type of amelo genesis imperfecta is characterized by normal enamel thickness with the appearance of white opaque areas on the incisal surfaces. Another important fact is the associa tion of amelogenesis imperfecta with other features, com prising a systemic disease or syndrome. 11 One such entity is known as enamel renal syndrome. 4 De la DureMolla et al. 4 have established an oral diagnosis criteria which includes clinical, radiographic, and microscopic features characteristic of this syndrome, along with the presence of renal abnormalities. Almost all the findings in our case fit these criteria except for few mentioned below. Radio graphically, an abnormal pathway of eruption was not evident in the second molars, and thickening of the max illary or nasal sinus lining was not observed. Microscop ically, the cellular cementum layer characteristic of this syndrome could not be seen. The diagnosis of enamel renal syndrome with associated amelogenesis imperfec ta, nephrolithiasis and hypocitraturia was made in this case, as most of the criteria were fulfilled, nephrolithiasis was evident in the ultrasound, and hypocitraturia was ob served in the urine analysis.
A renal ultrasound is now recommended in cases with such oral findings. 14 Abnormalities in the interstitial ma trix have been hypothesized to be the causative factor of dystrophic calcification in the kidney and of enamel ab normalities. 15 Low urinary citrate levels indicate that stone formation is more likely, because urinary citrate inhibits stone formation by forming soluble complexes with calci um. 16 Other relevant findings in such cases are localized aggressive periodontitis, gingival fibromatosis, and soft tissue calcifications, as described by Kantaputra et al. 5,17 Hence, they coined the term enamelrenalgingival syn drome. In the present case, localized periodontitis was ev ident, but the clinical findings did not justify a diagnosis of gingival fibromatosis and histopathological analysis did not reveal any soft tissue calcifications. However, the

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severity of gingival fibromatosis in such cases can vary even within the same mouth. 18 Thus, the present case was diagnosed with enamel renal syndrome, which underscores the fact that all such cases may not necessarily present with gingival abnormalities, as has been reported earlier. 4,17 Enamel renal syndrome is a rare autosomal disorder that has been proven to be associated with mutations in the FAM 20A gene. 4,5,17 However, the mutation test was not feasible in the present case.
Detecting an accessory mental foramen on the right side of the mandible was relevant, because it is a rare finding. 19 It is important to be aware of variations of the mental fora men in order to achieve successful anaesthesia that avoids nerve injury during periodontal or maxillofacial surgeries and dental implant placement. 20 It was observed that vol umerendered images were more useful in detecting ac cessory foramina and localized aggressive periodontitis.
Based on the findings of ultrasonography and other di agnostic modalities, the patient was informed that he had a higher risk of renal stone formation and was referred to a nephrologist for the necessary preventive treatment. Long term followup is imperative for patients with this condition, as some patients may eventually suffer from serious renal dysfunction. 9 In conclusion, an adequate knowledge of diseases that involve both dental and medical factors is indispensable for making the correct diagnosis and ensuring comprehen sive treatment. Volumerendered images from CBCT scans can be very valuable in detecting certain abnormalities.