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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

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Year : 2019  |  Volume : 23  |  Issue : 4  |  Page : 126-129

Association of enamel-renal syndrome with sialolith: A rare entity

1 Department of Oral and Maxillofacial Surgery, Mahe Institute of Dental Sciences and Hospital, Puducherry, India
2 Department of Oral Medicine, King Khalid University College of Dentistry, Abha, Kingdom of Saudi Arabia
3 Department of Oral Pathology and Microbiology, Mahe Institute of Dental Sciences and Hospital, Puducherry, India
4 Department of Orthodontics, Mahe Institute of Dental Sciences and Hospital, Puducherry, India

Date of Submission13-Jan-2018
Date of Acceptance29-Dec-2018
Date of Web Publication22-Feb-2019

Correspondence Address:
Manickam Selvamani
Department of Oral Pathology and Microbiology, Mahe Institute of Dental Sciences, Mahe, Puducherry
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jomfp.JOMFP_9_18

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Amelogenesis imperfecta (AI) is a disease primarily affecting amelogenesis, but other various aberrations have been reported in association with this entity. Enamel-renal syndrome (ERS) is a very rare disorder associating AI with nephrocalcinosis. It is known by various synonyms such as AI nephrocalcinosis syndrome, MacGibbon syndrome, Lubinsky syndrome and Lubinsky–MacGibbon syndrome. The purposes of this article are to describe other dental anomalies which are rarely associated with AI making the diagnosis of AI a complex disorder and also to report a rare case of MacGibbon syndrome presented with sialolith of submandibular gland duct which is the first reported case in the literature.

Keywords: Amelogenesis imperfecta, impacted teeth, nephrocalcinosis, sialolith

How to cite this article:
Manoj V, Sandeepa N C, Selvamani M, Panjami M. Association of enamel-renal syndrome with sialolith: A rare entity. J Oral Maxillofac Pathol 2019;23, Suppl S1:126-9

How to cite this URL:
Manoj V, Sandeepa N C, Selvamani M, Panjami M. Association of enamel-renal syndrome with sialolith: A rare entity. J Oral Maxillofac Pathol [serial online] 2019 [cited 2022 Jan 21];23, Suppl S1:126-9. Available from: https://www.jomfp.in/text.asp?2019/23/4/126/252740

   Introduction Top

Amelogenesis imperfecta (AI) is a genetic disorder comprising a group of developmental conditions affecting the structure and clinical appearance of enamel. Generalized involvement of the teeth in a more or less equal manner is seen in AI. It may also be presented with morphologic or biochemical changes in other parts of the body, thus AI can exist in isolation or associated with other abnormalities or as a part of syndromes. The prevalence of this disorder was reported to be 1:700–1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralized, or both and teeth affected may be discolored, sensitive, or prone to disintegration.[1]

AI may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. The syndrome of enamel-renal syndrome (ERS) (AI with nephrocalcinosis) has been previously described in 15 cases of both consanguineous and nonconsanguineous family. Other than pulp calcification and nephrocalcinosis, calcification in other tissues in AI is not described in the literature. Here, we report a unique case of MacGibbon syndrome. The patient also had other abnormalities such as multiple missing teeth, impacted teeth and follicular cyst, kidney stones and a rare finding of sialolith of submandibular duct. The patient reported to us with symptoms of sialadenitis. Further history, clinical examinations and investigation revealed all features constituting ERS.

   Case Report Top

A 29-year-old female patient reported to us with a chief complaint of pain in the right lower third of the face for 7 days. Pain was continuous and was aggravated on taking food with the onset of swelling in the lower third of the face. She was on analgesics for pain and found mild relief. She also complained of multiple missing teeth and yellowish discoloration of the teeth since childhood. Family history revealed no history of consanguineous marriage of parents. She was the eldest of the three children. She revealed similar condition of the teeth in her younger brother. Her younger sister was normal.

On general physical examination, the patient was moderately built and poorly nourished. Extraoral examination did not reveal any abnormality except for the mild swelling in the right submandibular region. On bimanual palpation, there was a mild swelling in the submandibular region. It was oval in shape and around 1 cm × 0.5 cm in dm and soft in consistency. On palpation, anterior floor of the mouth was tender, and an area of firm consistency was noted of measuring 3 mm × 1.5 mm in dimension. Hard tissue examination revealed missing 11, 21, 23, 12, 13, 31, 32, 33, 34, 35, 41, 42, 43, 44 and 45. There was crown with respect to 14, 24 and 25 [Figure 1]. All the teeth were hypoplastic with yellowish discoloration. The provisional diagnosis of sialolith with sialadenitis of submandibular gland was given. Considering the features of enamel hypoplasia and family history, AI was included.
Figure 1: Maxillary and mandibular arch showing missing anterior teeth yellowish discoloration of the teeth

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Mandibular occlusal radiograph was taken which showed radiopaque area of 2 mm × 1.5 mm in dimension oval-shaped structure in the anterior part [Figure 2]. Panoramic radiograph showed reduced enamel thickness of all teeth. Multiple teeth were impacted and showed hypoplastic enamel. 12, 15, 17, 18, 23, 28, 31, 34, 35, 38, 41, 43, 44, 45, 47 and 48 were impacted. Loss of coronal structure was noted in relation to 37 with well-defined periapical radiolucency. Pericoronal radiolucency was noted with respect to 38 and 48. Oval-shaped radiolucency was noted in the anterior aspect of mandible near the alveolar crest suggestive of sialolith [Figure 3].
Figure 2: Occlusal radiograph showing radiopaque structure in the anterior floor of the mouth

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Figure 3: Panoramic radiographic showing hypoplastic enamel, pulp stones, multiple impacted teeth, hyperplastic follicle

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The patient was given antibiotics for the sialadenitis. Sialolith was surgically removed under LA following 3 days [Figure 4]. Postoperative course was uneventful. As her medical history revealed episodes of back pain, the patient was referred to a physician. She was advised investigation following clinical examination. Computed tomography revealed multiple calcifications in the kidney and ovarian cyst. Considering these entire features, the patient was diagnosed to have ERS. 38 and 48 with enlarged follicular space were treated surgically. The patient was advised for prosthetic replacement of missing teeth. Furthermore, the patient was referred to a nephrologist for the evaluation of kidney stones.
Figure 4: (a) Computed tomography showing calcifications in the right and left kidney. (b) Photograph showing intraoperative picture showing sialolith and sialolith after surgical removal

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   Discussion Top

AI is genetically and clinically heterogeneous inherited dental enamel defects. Based on type of inheritance and clinical description of the condition, 14 different AI subtypes have been described. Now, the genetic classification, which is based on the underlying molecular changes is given increased importance than clinical classification.[1],[2] Although AI is commonly described as an isolated trait affecting dental enamel, it may be observed in association with a number of dental and/or systemic disorders.[3]

Various dental anomalies associated with AI are unerupted teeth, missing teeth, anterior open bite, pulpal calcifications, crown and root resorption, cementum deposition, truncated roots, taurodontism and gingival overgrowth.[3]

A variety of nonenamel manifestations are found to be segregated with enamel defect. It is not clear whether these nonenamel manifestations are due to tissue-specific expression of the gene as in case of pulp calcification, where calcification is supposed to be due to expression of the mutated gene in pulp tissue or as secondary effects.[4]

In 1972, MacGibbon described many cases where enamel defects and nephrocalcinosis were found to be associated and listed under the name “AI and nephrocalcinosis,” or alternatively as “Enamel-Renal Syndrome” (ERS, OMIM 204690).[5]

ERS is described as “rare disease” by the Office of Rare Diseases (ORD) of the National Institutes of Health. Cases of ERS have been reported in approximately 15 consanguineous as well as nonconsanguineous families.[5]

The common oral characteristics found to be associated and gives suspicion of ERS are the presence of thin or absent enamel, delayed tooth eruption and presence of pulpal calcifications.[6]

There are two hypotheses which explained the association of nephrocalcinosis in AI patients. The first hypothesis describes that calcium deposition is due to defect in the interstitial matrix.[5] Another hypothesis says that many of the dental proteins that were believed to be tissue-specific may be expressed in more than dental tissues and nondental tissues, and the role of these proteins in calcium and phosphate metabolism may be the attributing factor. Further research on the role of these proteins in calcium and phosphate metabolism has to be investigated.[7]

It is also possible that patients are wrongly diagnosed as ERS. Other than ERS, renal disease and enamel defects can be presented together. It was found that 58.3% of renal disease patients have abnormal enamel.[8]

Importantly, kidney regulates the calcium and phosphate homeostasis. Various renal proteins such as carbonic anhydrase II, the acid–base exchangers AE2, NBCe1 and NHE1 which are important in maintaining the systemic pH homeostasis are also expressed during amelogenesis.[9]

Literature also has described case reports of calcifications in gingiva and lungs in AI patients.[10]

It was found that FAM20A recessive mutations are responsible for ERS and AI with gingival hyperplasia. It was hypothesized that FAM20A is an additional kinase with specific targets directed in mineralization, calcium transport and proteoglycan synthesis. Although the reported clinical features of ERS primarily involve the orodental tissues and kidneys, FAM20A expression has been detected with the help of RT-PCR in additional tissues. Liver, lung, heart, stomach, placenta, parathyroid, thymus and kidney are those additional organs where FAM20 expression has been observed.[11]

AI occurs either in isolation or as part of a syndrome such as Jalili syndrome, Raine syndrome, epidermolysis bullosa and tricho–dento–osseous syndrome. Severe hypoplastic enamel constitutes the first element of differential diagnosis. Isolated association, such as AI and gingival fibromatosis, AI and hamartoma and AI and delayed eruption, may reflect other rare AI diseases. AI and hamartoma have been reported isolated or in several syndromes such as Cowden syndrome, von Recklinghausen disease and familial tuberous sclerosis.[11]

In our case, there were multiple missing teeth, especially in the anterior region. The clinical feature which was first striking was missing teeth than discoloration. The differential diagnosis which can be considered in our case was hereditary ectodermal dysplasia considering her family history and dental condition. AI in isolation or part of syndrome also can be considered.

Unique case of ERS is described here with a rare association of sialolith. Various hypothesis and genetic factors behind ectopic calcification in AI are discussed in the literature. This is the first case of AI presented with calcification in a salivary gland. Our case showed hypoplastic type of AI, multiple impacted teeth, hyperplastic follicle and pulp stones which make to consider AI as a syndrome itself. Additional feature of nephrocalcinosis was diagnosed during our examination based on her history of recurrent back pain. The patient reported to us for the treatment of sialadenitis, and a case of ERS was diagnosed with a rare presentation of salivary gland calcification. The theories which are responsible for nephrocalcinosis can be applied for the salivary gland calcification. It is also possible that sialolith was merely an associated finding in the patient. Detailed study and expression of various proteins responsible for calcification may help to know the etiology for calcification in salivary gland tissue in AI patients.

   Conclusion Top

Rare association of AI with sialolith is described here. The knowledge regarding these rare associations is important to come to the early diagnosis and prediction of outcome and prognosis of disease condition.

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.

   References Top

1 Nusier M, Yassin O, Hart TC, Samimi A, Wright JT. Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:220-30.  Back to cited text no. 1
Witkop CJ Jr. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: Problems in classification. J Oral Pathol 1988;17:547-53.  Back to cited text no. 2
Crawford PJ, Aldred M, Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J Rare Dis 2007;2:17.  Back to cited text no. 3
Collins MA, Mauriello SM, Tyndall DA, Wright JT. Dental anomalies associated with amelogenesis imperfecta: A radiographic assessment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:358-64.  Back to cited text no. 4
Kala Vani SV, Varsha M, Sankar YU. Enamel renal syndrome: A rare case report. J Indian Soc Pedod Prev Dent 2012;30:169-72.  Back to cited text no. 5
Lubinsky M, Angle C, Marsh PW, Witkop CJ Jr. Syndrome of amelogenesis imperfecta, nephrocalcinosis, impaired renal concentration, and possible abnormality of calcium metabolism. Am J Med Genet 1985;20:233-43.  Back to cited text no. 6
Elizabeth J, Lakshmi Priya E, Umadevi KM, Ranganathan K. Amelogenesis imperfecta with renal disease – A report of two cases. J Oral Pathol Med 2007;36:625-8.  Back to cited text no. 7
Subramaniam P, Gupta M, Mehta A. Oral health status in children with renal disorders. J Clin Pediatr Dent 2012;37:89-93.  Back to cited text no. 8
Lin HM, Nakamura H, Noda T, Ozawa H. Localization of H(+)-ATPase and carbonic anhydrase II in ameloblasts at maturation. Calcif Tissue Int 1994;55:38-45.  Back to cited text no. 9
Kantaputra PN, Kaewgahya M, Khemaleelakul U, Dejkhamron P, Sutthimethakorn S, Thongboonkerd V, et al. Enamel-renal-gingival syndrome and FAM20A mutations. Am J Med Genet A 2014;164A: 1-9.  Back to cited text no. 10
de la Dure-Molla M, Quentric M, Yamaguti PM, Acevedo AC, Mighell AJ, Vikkula M, et al. Pathognomonic oral profile of enamel renal syndrome (ERS) caused by recessive FAM20A mutations. Orphanet J Rare Dis 2014;9:84.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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