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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 8  |  Issue : 2  |  Page : 92-96

Fanconi anemia in pediatric dentistry: Case report and review of literature


Department of Pedodontics and Preventive Dentistry, Dr. R Ahmed Dental College and Hospital, Kolkata, West Bengal, India

Date of Web Publication8-Jun-2017

Correspondence Address:
Rahul Kaul
Room No. 2C, Department of Pedodontics and Preventive Dentistry, Dr. R Ahmed Dental College and Hospital, Kolkata - 700 014, West Bengal
India
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DOI: 10.4103/srmjrds.srmjrds_83_16

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  Abstract 

Management of bleeding disorders poses a challenge to dentists. These conditions can be inherited, acquired, or congenital are associated with an increased risk of hemorrhage, poor wound healing, and infection. Fanconi anemia (FA) is a rare autosomal recessive disease which belongs to a group of chromosome break up or DNA repair disorders. Hematologic abnormalities represent the most prevalent pathologic manifestation of FA. Herein, we report a case of FA in which various classical signs of the disease were present. We have given emphasis on oral manifestations and the role of a pedodontist in making an early diagnosis and providing comprehensive care for the maintenance of oral health of the affected individuals.

Keywords: Bleeding disorders pedodontist, management, treatment considerations


How to cite this article:
Kaul R, Jain P, Saha S, Sarkar S. Fanconi anemia in pediatric dentistry: Case report and review of literature. SRM J Res Dent Sci 2017;8:92-6

How to cite this URL:
Kaul R, Jain P, Saha S, Sarkar S. Fanconi anemia in pediatric dentistry: Case report and review of literature. SRM J Res Dent Sci [serial online] 2017 [cited 2021 Jul 31];8:92-6. Available from: https://www.srmjrds.in/text.asp?2017/8/2/92/207658


  Introduction Top


Fanconi anemia (FA) is a rare autosomal recessive disease which belongs to a group of DNA repair or chromosome break up disorders. It is characterized by congenital malformations, progressive bone marrow hypoplasia, and a high risk of malignancies. Current literature describes the prevalence of 1:360,000 with a female-to-male ratio of 1:2.[1],[2] As of now, fifteen genetic subtypes have been distinguished. Most of FA patients belong to subtypes A, C, or G, whereas a lesser number is distributed over the remaining twelve subtypes.[3]

Individuals with FA display several congenital defects, but approximately 25%–40% of FA patients appear normal physically. In the majority of cases, manifestations of FA in the form of physical signs, such as abnormal skin pigmentation, short stature, thumb and radial anomalies, structural defects of the kidney, microcephaly, retarded and delayed development can be seen at birth and during early years of childhood.[4]

The most prevalent pathologic manifestation of FA are the hematologic abnormalities. The hematological complications include progressively higher pancytopenia, anemia, thrombocytopenia, leukopenia, macrocytosis, and fetal-like erythropoiesis.[5]

Bone marrow failure develops in approximately 75%–90% of FA patients, which ranges from mild to severe, during the first decade of life. In addition, most patients of FA develop varying degrees of hematological diseases, including myelodysplastic syndrome, acute myeloid leukemia (AML), and aplastic anemia. FA patients carry a risk of developing AML approximately 800-times higher than that of the general population, having a median age of onset of 14 years.[4]

The oral manifestations may be the presence of missing teeth, malpositioned teeth, supernumerary teeth, small teeth, abnormal root shapes, dental caries, gingivitis/periodontal disease, oral mucosal lesions, salivary gland dysfunction, and predisposition toward the development of oral cancers, especially squamous cell carcinoma (SCC). The tooth with the highest prevalence of agenesis is the maxillary central incisor. The permanent canine is the tooth with the highest prevalence of transposition.[6],[7]

Despite a myriad of problems, oral and dental findings have rarely been reported in patients of FA.[6],[7] In any complex disease process, there is always an involvement of multiple super specialties. A complete coordination between parents and super-specialists is required to obtain a successful treatment outcome.

In this article, we report a case of FA, highlighting the main oral manifestations and discussing their management, which will positively affect the health of patients with FA.


  Case Report Top


A 3-year-old Asian female child reported to the Department of Pedodontics And Preventive Dentistry. The child had been diagnosed with FA with the help of stress test using mitomycin C for the detection of FA [Figure 1] and [Figure 2].
Figure 1: Three year old girl child known case of Fanconi anemia

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Figure 2: Fanconi anemia diganosed by stress test using mitomycin C

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Patient's parents had a consanguineous marriage. Neither the parents nor any of the child's siblings were affected by FA. The child was born through a cesarean operation after 38 weeks of pregnancy and had a low birth weight.

General examination revealed certain congenital abnormalities like sandal toe in the right foot, hypoplasia of thumbs in both hands and deformed forearms [Figure 3],[Figure 4],[Figure 5],[Figure 6]. Growth was retarded. No pigmentation of skin was observed.
Figure 3: Lower limb showing sandle toe

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Figure 4: Upper limb showing hypoplastic thumb

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Figure 5: PA view of upper limb


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Figure 6: AP view of upper limb showing deformed forearms

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Blood examination reports revealed progressive thrombocytopenia [Table 1].
Table 1: Laboratory findings on first visit


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The patient was conscious but not fully cooperative with well-developed cognition during general physical examination. Patients parents reported that child was having spontaneous gingival bleeding at night for the past 1 week. Intra-oral examination revealed poor oral hygiene and a few carious teeth. Radiographs were required but could not be taken as radiation exposure increases the risk of tumor production in FA patients.

Treatment given was palliative. We prescribed 1% chlorhexidine gel for local application and provided parental counseling on the necessity of maintaining proper oral hygiene of the child. Proper technique of brushing was demonstrated. The child has been kept on regular 6-month follow-up. Follow-up visits showed an improvement in the oral health of the child.


  Discussion Top


FA is primarily a autosomal or X-chromosomal recessive chromosome instability disorder due to germ-line mutations. About 2% of FA cases are X-linked recessive. As of now seventeen FA or FA-like genes have been identified. These include FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCP (SLX4), FANCS (BRCA1), RAD51C, and XPF. FANC B is the one exception to FA being autosomal recessive, as this gene is on the X chromosome.[8],[9],[10]

These seventeen gene products appear to function in a common cellular pathway, termed the FA pathway, thought to coordinate a complex mechanism that enmarks elements of three classic DNA repair pathways, namely homologous recombination, mutagenic translesion synthesis, and nucleotide excision repair in response to any genotoxic insult. FA patients with mutations in any of these FA genes share a characteristic clinical as well as cellular phenotype.[11]

A myriad of clinical findings is observed in FA patients. FA being a chromosomal instability disorder caused by mutations in genes regulating the replication-dependent removal of interstrand DNA crosslinks. These patients accumulate defective DNA at an increased rate. This defective or unrepaired DNA leads to activation of pro-apoptotic pathways, causing depletion of hematopoietic stem cells and resultant pancytopenia. Moreover, defective DNA repair in FA cells can lead to mutations and translocations which in turn inactivate cell cycle barriers leading to AML and other blood as well as solid tumors. The above-mentioned sequence of events is responsible for the perplexing phenomenon that the same population of cells can either be diminished (presenting as anemia) or hyper-represented (presenting as cancer). It has been observed that bone marrow failure manifests itself earlier in development, on an average at the age of 7 years, and is the major cause of death, occurring around the age of 16 years. Contrary to this, the median age of cancer onset is 14 years, representing a major hindrance for patients having received bone marrow transplant to treat the anemia.[11]

Approximately half of children with FA have congenital skeletal abnormalities, frequently of the thumb and forearm. The thumbs are usually smaller (hypoplastic), duplicated, or absent. The radius of the forearm may also be smaller or absent. The short stature of these patients is attributed to deficiency of growth hormone, affecting approximately 80% of FA individuals.[12] Koubik et al. found that bone and tooth age in patients with FA was lower than their chronological age. In the present case report also, the child had a short stature and had malformation of arms, feet as well as hands. As for dental treatment, it is the role of a pedodontist to bring about this coordination; perfectly depicted by “kidznteenz pediatric pentagon”[Figure 7].[7],[8] FA individuals exhibit other clinical problems, such as hearing loss and ear anomalies as well as reduced fertility.[12]
Figure 7: Kidteenz pediatric pentagon

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Patients with FA usually have a short life cycle, usually three decades, because of the development of severe health problems, such as AML, bone marrow failure, and solid tumors. Treatment of choice is transplantation when progressive bone marrow failure occurs, since this treatment requires the use of chemotherapy, especially immunosuppressant drugs and radiotherapy, thereby making them vulnerable to the development of carcinomas, especially of head and neck region. In patients with FA, there is also a high risk (11.7%) for the development of oral SCC.[13],[14]

The main FA-associated oral manifestations include gingivitis, periodontitis, rotated teeth, and agenesis. The high predisposition to periodontal disease and gingivitis in patients with FA can be attributed to frequent immune deficiency, anemia, and leukopenia in affected individuals. Aggressive periodontitis is seen with increased horizontal loss of alveolar bone. Deficiency of leukocytes and presence of pathogenic microorganisms such as aggregatibacter actinomycetemcomitans are the etiological factors for this condition.[15] Moreover, treatment with immunosuppressant agents, such as corticosteroids, further reduces the immunological defense leading to higher predisposition toward periodontal disease.[16] Thrombocytopenia can be held culpable for gingival bleeding observed in these patients.[2] de Araujo et al. concluded that inadequate oral hygiene was the most common factor associated with periodontal disease and gingivitis, and no significant association of number of platelets was found with periodontal disease or gingivitis in patients of FA.[17]

Reports suggest that 35%–66% of FA patients develop dental caries and gingival problems.[18],[19]

Recurrent aphthous ulcers (RAUs) and eruption cysts are most common oral soft tissue lesions observed in individuals with FA. RAU is chief complaint for which patient visits dental clinic more frequently. RAUs are formed due to hematological condition, particularly neutropenia and anemia, which is justified by the fact that there is an improvement in the condition of recurrent ulcers in the weeks after blood transfusions.[18],[20]

Patients with FA require close follow up of an interdisciplinary team, including an endocrinologist to assess and treat developmental disorders, a Hematologist for the control of anemia and an Oncologist for the diagnosis and treatment of tumors. A heterogeneous pattern has been seen regarding the oral manifestations of FA, which requires that the concerned pedodontist has appropriate training and participates in the interdisciplinary team responsible for the diagnosis and treatment of these individuals.

All standard hematological tests should be carried out to rule out blood related diathesis before the introduction of any invasive procedure at the dental office.

Patients with FA are more prone to get infections, so proper precautions should be taken to avoid any situation that might put them at risk of infection or bleeding. Antibacterial mouthwash and oral antibiotics should be prescribed before dental procedures. Before any invasive procedure or minor surgical procedure, it is mandatory to check the level of platelets and maintain them at an optimum quantity to achieve proper hemostasis. If the desired levels of platelets are not achieved, a platelet replenish therapy has to be given well before the desired treatment procedures. In the case of extractions or minor surgeries, use of local hemostatic agents such as BLOTOCLOT/Gelfoam/bone wax will be beneficial in attaining complete hemostasis.

Dental treatment should be specific and restricted to infection control. Providing oral health care to these patients is difficult for many reasons. Radiographs are not advised in FA patients as they lead to induction of tumors, thereby making proper diagnosis of oral diseases difficult.

Treatment of acute dental infections should be carried out immediately and oral focii of infection should be eliminated, making sure that there is no source of infection to ascertain the overall health and wellbeing of the patient. It is always preferable to extract carious teeth than to perform pulp therapies so as to effectively reduce the chance for infection to spreading periapically, which can cause more complications in immunosuppressive patients. Mildly carious teeth need to be restored and whereas grossly carious/decayed teeth should be removed before the patient has to go for transplantation.

Chronic periodontitis is a severe focal infection and considered a potential risk of systemic infection in patients with FA. Therefore, some clinicians prefer using antibiotic prophylaxis before any periodontal treatment so as to minimize the risk of systemic infection. Management of periodontal problems is difficult in patients with FA as they have a greater bleeding tendency. A thorough clinical examination needs to be performed to determine the number of remaining teeth, probing depth for each tooth, mucogingival junction level and the width of keratinized gingiva.

Effective oral health measures include the caries risk assessment that includes the assessment of salivary quality, quantity, buffering capacity as well as monitoring gingival and plaque indices. Based on these readings obtained, we have to make sure that we stick to a proper oral hygiene protocol that will benefit the patient from exposure to new lesions as well as the progression of the existing lesions.

Home oral hygiene measures should be encouraged which include a fluoridated toothpaste and fluoride mouth rinse that serve as an effective barrier to protect the teeth as well as gingiva from harmful loads of bacterial plaque.[17]

Oral rehabilitative treatment includes removable partial dentures and fixed partial dentures which need to be given with utmost care and after demonstrating proper oral hygiene methods.

Properly planned preventive phase that prevents future complex treatment, can be effectively provided by a pediatric dentist. Genetic testing is mandatory in all cases of suspected FA, siblings, parents, and close blood relatives. Pediatric dentists are in a unique position to identify early changes or lesions associated with FA in the oral cavity. Pediatric dentists form an indespensible part of the multidisciplinary team involved in the treatment and hence should be aware of the etiopathogenesis of the diverse oral conditions observed in FA. Patients should be motivated for regular follow-ups to maintain good periodontal health, thereby reducing the incidence of caries. Periodic monitoring of the oral health of these individuals should be done.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
Schofield ID, Worth AT. Malignant mucosal change in Fanconi's anemia. J Oral Surg 1980;38:619-22.  Back to cited text no. 2
    
3.
Stoepker C, Hain K, Schuster B, Hilhorst-Hofstee Y, Rooimans MA, Steltenpool J, et al. SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. Nat Genet 2011;43:138-41.  Back to cited text no. 3
    
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D'Andrea AD. Susceptibility pathways in Fanconi's anemia and breast cancer. N Engl J Med 2010;362:1909-19.  Back to cited text no. 4
    
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8.
Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B, et al. PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol 2009;19:524-9.  Back to cited text no. 8
    
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Koubik AC, Franca BH, Ribas Mde O, de Araujo MR, Mattioli TM, de Lima AA. Comparative study of chronological, bone, and dental age in Fanconi's anemia. J Pediatr Hematol Oncol 2006;28:260-2.  Back to cited text no. 11
    
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Dokal I, Vulliamy T. Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev 2008;22:141-53.  Back to cited text no. 12
    
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Salum FG, Martins GB, de Figueiredo MA, Cherubini K, Yurgel LS, Torres-Pereira C. Squamous cell carcinoma of the tongue after bone marrow transplantation in a patient with Fanconi anemia. Braz Dent J 2006;17:161-5.  Back to cited text no. 13
    
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Nowzari H, Jorgensen MG, Ta TT, Contreras A, Slots J. Aggressive periodontitis associated with Fanconi's anemia. A case report. J Periodontol 2001;72:1601-6.  Back to cited text no. 14
    
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Engel JD, Ruskin JD, Tu HK. Hematologic management of a patient with Fanconi's anemia undergoing bone grafting and implant surgery. J Oral Maxillofac Surg 1992;50:288-92.  Back to cited text no. 15
    
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de Araujo MR, de Oliveira Ribas M, Koubik AC, Mattioli T, de Lima AA, França BH. Fanconi's anemia: Clinical and radiographic oral manifestations. Oral Dis 2007;13:291-5.  Back to cited text no. 16
    
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Açikgöz A, Ozden FO, Fisgin T, Açikgöz G, Duru F, Yarali N, et al. Oral and dental findings in Fanconi's anemia. Pediatr Hematol Oncol 2005;22:531-9.  Back to cited text no. 17
    
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Tekcicek M, Tavil B, Cakar A, Pinar A, Unal S, Gumruk F. Oral and dental findings in children with Fanconi anemia. Pediatr Dent 2007;29:248-52.  Back to cited text no. 18
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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