|Year : 2016 | Volume
| Issue : 1 | Page : 35-39
Orodental manifestations of enamel renal syndrome in siblings: A rare case report
Nagaraju Kamarthi1, Suhasini Gotur Paklakshappa2, Jyoti Sharma1
1 Department of Oral Medicine and Radiology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India
2 Department of Oral Pathology and Microbiology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India
|Date of Web Publication||21-Jul-2016|
Department of Oral Medicine and Radiology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. Hypoplastic AI can occur per se or in a variety of ectodermal syndromes and metabolic disorders. Enamel renal syndrome (ERS) is a very rare disorder associating hypoplastic AI with nephrocalcinosis. Since nephrocalcinosis is often asymptomatic, the orodental findings and dental radiographic features play a key role in the diagnosis of this extremely rare inherited disorder. This paper describes the orodental manifestations of ERS in siblings who were born of consanguineous parents.
Keywords: Enamel renal syndrome, hypoplastic amelogenesis imperfecta, nephrocalcinosis, orodental
|How to cite this article:|
Kamarthi N, Paklakshappa SG, Sharma J. Orodental manifestations of enamel renal syndrome in siblings: A rare case report. Int J Oral Health Sci 2016;6:35-9
|How to cite this URL:|
Kamarthi N, Paklakshappa SG, Sharma J. Orodental manifestations of enamel renal syndrome in siblings: A rare case report. Int J Oral Health Sci [serial online] 2016 [cited 2019 Dec 7];6:35-9. Available from: http://www.ijohsjournal.org/text.asp?2016/6/1/35/186665
| Introduction|| |
Amelogenesis imperfecta (AI) is a heterogeneous group of conditions, genomic in origin, affecting the structure and clinical appearance of the enamel of all or nearly all the teeth in a more or less equal manner. It may be associated with morphologic or biochemical changes elsewhere in the body, having an autosomal dominant, autosomal recessive, or X-linked modes of inheritance. 
Initially described by MacGibbon in 1972, in a brother and sister, enamel renal syndrome (ERS) is characterized by hypoplastic AI and nephrocalcinosis (deposition of calcium in renal tissue).  It is known by various synonyms such as AI nephrocalcinosis syndrome, Online Mendelian inheritance in Man 204690,  MacGibbon syndrome, Lubinsky syndrome, and Lubinsky-MacGibbon syndrome. 
| Case Report|| |
A 32-year-old male patient reported with the chief complaint of rapid wear and yellowish discoloration of teeth. On clinical examination [Figure 1], the teeth showed a yellow-brown hue, open contact points, and relative microdontia, with a significant generalized attrition. The posterior teeth lacked the cuspal morphology and appeared flat on the occlusal surface. The teeth totally appeared to lack enamel formation. 17 and all the third molars were clinically missing. On taking family history, he revealed that his younger brother, who is aged about 30 years, also has similar dental abnormalities. The intraoral examination of the younger brother revealed multiple missing teeth, relative microdontia, and small mandible [Figure 2]. The teeth which were present had the shape and color of dentin with a yellow-brown hue, open contact points, and the crowns were tapering toward the incisal occlusal surface. Flat cusps on posterior teeth were noted similar to his elder brother. The teeth totally appeared to lack enamel formation. On careful examination, both the siblings showed enlargement involving interdental papilla and marginal gingiva, indicating mild gingival fibromatosis. They also gave a history of delayed eruption sequence. In spite of severe attrition noted, they only complained of mild sensitivity. The family history revealed consanguineous (first-degree cousins) parents. Both pregnancies were unremarkable. No health problems were observed during the perinatal period and childhood. General physical examination was noncontributory.
|Figure 1: Intraoral photograph of (a) frontal view, (b) right lateral, (c) left lateral, (d) maxillary occlusal view of the elder sibling showing yellow-brown discoloration of teeth, severe attrition, and mild gingival enlargement|
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|Figure 2: Clinical photographs of younger sibling (a) profile view showing micrognathic mandible (b) intraoral frontal view, (c) maxillary occlusal view, (d) mandibular occlusal view showing yellow-brown discoloration of teeth, multiple unerupted teeth, severe attrition, and lack of cuspal morphology in posterior teeth|
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Panoramic radiograph was performed for both the siblings. Orthopantomography (OPG) of the elder sibling [Figure 3] showed lack of contrast between enamel and dentine in all the teeth including the impacted ones (28, 38, and 48), altered eruption pathway, crown resorption of unerupted teeth (17), and intracoronal pulp calcifications in few teeth. OPG of the younger [Figure 4] revealed multiple unerupted permanent teeth, lack of contrast between enamel and dentine in all the teeth, intracoronal pulp calcifications, impacted posterior teeth with hyperplastic follicle, root dilacerations, and crown resorption of unerupted teeth.
|Figure 3: Orthopantomography of the elder brother showing lack of contrast between enamel and dentine in all the teeth including the impacted ones, altered eruption pathway and crown resorption of unerupted teeth, and intracoronal pulp calcifications in few teeth|
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|Figure 4: Orthopantomography of the younger revealed multiple unerupted permanent teeth, lack of contrast between enamel and dentine in all the teeth, intracoronal pulp calcifications, impacted posterior teeth with hyperplastic follicle, root dilacerations, and crown resorption of unerupted teeth|
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These orodental and radiographic findings in siblings born to consanguineous parents were strongly suggestive of ERS, and the patient was advised for the ultrasound examination of the renal system. Ultrasound of the elder brother confirmed multiple hyperechoic areas in both the kidneys, suggesting renal stones [Figure 5]. Younger brother was unwilling for the examination. Hence, the final diagnosis of ERS was made based on the orodental and ultrasound findings. Further, the patients were referred to medical examination and management, pondering the risk of progressive renal failure. Full mouth rehabilitation was done for the elder brother, considering his chief complaint of poor dental esthetics and teeth sensitivity [Figure 6]. Complete rehabilitation with overdentures was advised for the younger brother. Both the patients were directed for regular follow-up, but only elder brother was available for the follow-up visits. A follow-up of 3 years in the elder sibling revealed no renal manifestations till date.
|Figure 5: Ultrasonography of the elder sibling showing stones in both the right and left kidneys|
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|Figure 6: Extensive endodontic treatment of the elder brother before prosthodontic rehabilitation|
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| Discussion|| |
AI, commonly described as an isolated trait, may be observed concomitantly with a number of variable dental and/or systemic disorders. ERS has been reported in children from consanguineous as well as nonconsanguineous families.  The consanguineous marriage of the sibling's parents in the present case report suggests an autosomal recessive inheritance.
Paradigms behind the etiopathogenesis of ERS include pleiotropism, abnormality in interstitial matrix leading to dystrophic calcification, expression of tissue-specific dental proteins in dental and nondental tissues, and symbiotic role of albumin and osteopontin.  Recessive mutations in the family with sequence similarities 20 member A (FAM20A) gene were identified as the cause of ERS and "Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS)." FAM20A plays a role in enamel secretion and maturation stages, although its distinct roles in amelogenesis and nephrocalcinosis remain to be discovered.  Mutations in genes amelogenin, enamelin, family with sequence similarity member H, kallikrein 4, and matrix metalloproteinase 20 have been described in association with AI, but none of the mutated proteins identified in AI patients has been found to be expressed in the kidney, suggesting the need for the further research in explaining the etiopathogenesis of ERS. 
Patients with ERS may have no renal complications until late childhood or early adulthood, with perhaps recurrent urinary infections, pyelonephritis, or renal colic, and the passage of a renal stone.  Although often asymptomatic, nephrocalcinosis can be associated or can lead to the impaired renal function, and untreated nephrocalcinosis is known to be associated with a significant morbidity. In ERS syndrome, no predisposing factors such as hypercalcemia and hypercalciuria have been found. On the contrary, hypocalciuria and low phosphate in urine and proteinuria have been reported. 
A review of the clinical cases in the literature indicates that AI associated with the key features of ERS/AIGFS has been reported, but named differently: Only AI, AI with inter-radicular dentine dysplasia, AI with gingival fibromatosis, AI with odontogenic fibroma-like hamartomas around nonerupted teeth, AI with crown resorption, and AI with unerupted teeth. To date, all together <100 cases have been reported in the world on ERS-like cases. Only 16 cases included a complete analysis of both dental/oral and renal phenotypes. Since the renal status was not systematically analyzed in these cases, ERS has been underestimated.  This syndrome is previously documented in four sibling pairs, ,,, the current case being the fifth, although few cases of AI associated with the key features of ERS in kindred are reported, but by other names. ,,,
Clinical diagnosis of ERS focuses on the association of orodental features and renal findings that may lead on to renal impairment. However, the oral phenotype is characteristic and in the absence of other co-segregating health problems, sufficient to clinically diagnose ERS and direct genetic testing to look for FAM20A recessive mutations. 
Orodental clinical features typical of FAM20A recessive mutations given by de la Dure-Molla et al.  are enlisted in [Table 1].
While individual features are not specific to ERS, they are pathognomonic when they occur together in children in the absence of other developmental abnormalities. Using the orodental clinical features listed in [Table 1], diagnosis can be made based solely on enamel defects and radiographic features observed on the panoramic radiograph. The dental radiographic images are per se diagnostic. 
Eruption of primary and permanent teeth is often delayed due to disturbances in the early morphogenetic events during odontogenesis. Even gingival hyperplasia and enlarged enamel follicle can impair the normal eruption process. 
The enamel defect in this condition, histologically and ultrastructurally, resembles that of autosomal recessive hypoplastic (enamel agenesis) type of AI. The affected enamel appears as irregular globular-calcified layer with hypoplastic, positively birefringent, generally aprismatic, porous and consists of loosely packed, randomly orientated, thin, ribbon-like crystals.  An abnormal thick layer of what appears to be cellular cementum covers the roots, especially in the inter-radicular area. Dentin is normal, but the dentino-enamel junction lacks its characteristic scalloped configuration. Histological analysis of gingival epithelium demonstrates elongated and thin papillae. Gingival connective tissue appears increasingly fibrous with depth, with the occurrence of focal, round ectopic calcification near the alveolar bone. Histopathological analysis of the pericoronal follicles of impacted teeth reveals calcified nodules similar to gingival ones.  However, histological examination was not carried out in the current case as both the patients were not willing for gingival biopsy and extraction of impacted teeth.
When ERS is suspected, the patient should be assessed by a dentist, nephrologist, and clinical geneticist. Confirmed cases require long-term follow-up as renal impairment remains a major concern for prognosis. Management of the orodental aspects can be extremely challenging and requires the input of multidisciplinary specialized dental team, especially when there are multiple unerupted teeth.
| Conclusion|| |
We have described the orodental manifestations in siblings with ERS. The orodental and the OPG findings supplemented with ultrasonography of kidneys were sufficient to diagnose the disorder as ERS. Since the oral manifestations in the absence of other developmental health problems is pathognomonic, dentists have a key role in the diagnosis and referral of patients to both nephrologists for renal assessment. Hence, dentists are expected to have a sound knowledge of this disorder for the early detection, thus to prevent the morbidity and mortality associated with this rare entity.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]