L'an\u00e9mie de Fanconi<\/a><\/h3><\/p>\n\n- L’an\u00e9mie de Fanconi (AF) est un trouble multisyst\u00e9mique caract\u00e9ris\u00e9 par un spectre d’anomalies cong\u00e9nitales, une insuffisance progressive de la moelle osseuse et une pancytop\u00e9nie, une forte susceptibilit\u00e9 \u00e0 la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb (LMA) et aux tumeurs solides. <\/li>
- L’AF est pr\u00e9sente dans le monde entier et touche 1 naissance sur 100 000 aux \u00c9tats-Unis. Elle est notamment plus fr\u00e9quente chez les Africains (environ 1 sur 22 000), estim\u00e9e \u00e0 1 sur 45 000 en Isra\u00ebl et la population gitane espagnole pr\u00e9senterait la plus forte pr\u00e9valence.<\/li><\/ul>\n\n
- L’AF est un syndrome cliniquement h\u00e9t\u00e9rog\u00e8ne d’insuffisance de la moelle osseuse, d’anomalies cong\u00e9nitales qui peuvent affecter tous les organes. <\/li>
- Les patients atteints d’AF peuvent souffrir de diverses malformations. Les anomalies cong\u00e9nitales comprennent des malformations du squelette (petite taille, microc\u00e9phalie ou pouce hypoplasique), des anomalies des organes (r\u00e9naux, ophtalmiques, auriculaires, cardiaques et g\u00e9nitaux) et des anomalies de la pigmentation de la peau, comme les taches caf\u00e9 au lait (tableau 1). <\/li>
- Jusqu’\u00e0 pr\u00e9sent, 23 g\u00e8nes ont \u00e9t\u00e9 impliqu\u00e9s dans l’AF caus\u00e9e par des mutations germinales dans un des multiples g\u00e8nes de l’AF (FANCA \u00e0 FANCV). Les mutations dans le g\u00e8ne FANCA sont les plus courantes et sont impliqu\u00e9es dans 60 \u00e0 65 % des cas signal\u00e9s. Toutes les mutations dans les g\u00e8nes de l’AF sont transmises de mani\u00e8re autosomique r\u00e9cessive, \u00e0 l’exception de FANCB et RAD51, qui sont transmises respectivement de mani\u00e8re li\u00e9e au chromosome X et de mani\u00e8re autosomique dominante. <\/li>
- Les prot\u00e9ines de l’AF interagissent dans une voie cellulaire commune et participent \u00e0 divers aspects de la r\u00e9paration de l’ADN, notamment la r\u00e9paration des liaisons transversales de l’ADN, la stabilisation g\u00e9nomique et la r\u00e9gulation des prot\u00e9ines en aval. Les d\u00e9fauts de l’une de ces prot\u00e9ines de l’AF entra\u00eenent une instabilit\u00e9 g\u00e9nomique, des m\u00e9canismes de r\u00e9paration de l’ADN d\u00e9fectueux et un risque accru de cancer.
\n<\/li>
- Les patients atteints de FA pr\u00e9sentant un dysfonctionnement h\u00e9matopo\u00ef\u00e9tique doivent g\u00e9n\u00e9ralement subir une greffe de moelle osseuse ou une greffe de cellules souches h\u00e9matopo\u00ef\u00e9tiques , qui est l’option th\u00e9rapeutique privil\u00e9gi\u00e9e. <\/li>
- L’une des complications les plus courantes apr\u00e8s une greffe de cellules souches h\u00e9matopo\u00ef\u00e9tiques est le d\u00e9veloppement de la maladie chronique du greffon contre l’h\u00f4te (cGVHD), qui est \u00e9galement un facteur de risque pour le d\u00e9veloppement de cancers, en particulier le carcinome \u00e9pidermo\u00efde buccal. La cGVHD est d\u00e9sormais reconnue comme une l\u00e9sion \u00e0 potentiel malin <\/li>
- \u00c9tant donn\u00e9 le large \u00e9ventail d’anomalies cliniques, les patients atteints d’AF n\u00e9cessitent une \u00e9valuation compl\u00e8te au moment du diagnostic. <\/li>
- L’AF peut \u00eatre difficle \u00e0 diff\u00e9rencier d’autres syndromes g\u00e9n\u00e9tiques, ce qui complique son diagnostic. L’expressivit\u00e9 variable de l’AF rend le diagnostic pr\u00e9coce difficile dans certains cas. <\/li>
- Une description clinique d\u00e9taill\u00e9e des alt\u00e9rations les plus fr\u00e9quentes trouv\u00e9es dans les diff\u00e9rents organes est donn\u00e9e par Moreno et al (2021). <\/li>
- Le diagnostic de laboratoire est \u00e9tabli par la positivit\u00e9 du test de cassure chromosomique lors de l’exposition \u00e0 des agents de r\u00e9ticulation de l’ADN. <\/li>
- Les autres m\u00e9thodes de diagnostic utilis\u00e9es sont le western blotting, l’amplification par PCR multiplexe et le s\u00e9quen\u00e7age de nouvelle g\u00e9n\u00e9ration. <\/li>
- Une fois le diagnostic confirm\u00e9, une surveillance \u00e0 vie des patients atteints d’AF est n\u00e9cessaire pour assurer un diagnostic pr\u00e9coce du cancer. Le conseil g\u00e9n\u00e9tique est essentiel. <\/li><\/ul>\n\n
CARACT\u00c9RISTIQUES CLINIQUES DE L’AN\u00c9MIE DE FANCONI<\/strong>
(adapted from Nalepa and Clapp 2018) <\/p>\n\n<\/div>\n\n\n\n- Malformations cranofaciales<\/li>
- Retard de d\u00e9veloppement<\/li>
- Petite taille<\/li>
- Hypodontie, petites dents<\/li>
- Saignement buccal<\/li>
- Gencives gonfl\u00e9es<\/li>
- L’association VACTERL<\/li>
- Pouce ou radius anormal<\/li><\/ul>\n<\/div>\n\n\n\n\n
- Ost\u00e9oporose<\/li>
- Insuffisance m\u00e9dullaire progressive<\/li>
- Malformations cardiaques<\/li>
- Malformations g\u00e9nito-urinaires et gastro-intestinales<\/li>
- Ectopie ou dysplasie r\u00e9nale<\/li>
- Dysfonction endocrienienne<\/li>
- Diminution de la fertilit\u00e9<\/li><\/ul>\n<\/div>\n<\/div>\n\n
- Environ un quart des patients atteints d’AF qui d\u00e9veloppent des tumeurs solides ne sont diagnostiqu\u00e9s comme tels qu’apr\u00e8s la d\u00e9couverte de leur cancer. <\/li>
- Par cons\u00e9quent, l’AF doit \u00eatre envisag\u00e9e dans les tumeurs malignes \u00e0 apparition pr\u00e9coce. L’apparition pr\u00e9coce du cancer de la bouche, telle que d\u00e9crite dans plusieurs rapports de cas (cit\u00e9s ci-dessous), peut servir d’indication pour envisager le diagnostic de l’AF chez les jeunes patients qui d\u00e9veloppent un HNSCC en l’absence de facteurs de risque.<\/li>
- L’AF peut entra\u00eener une insuffisance de la moelle osseuse. La transplantation de cellules souches h\u00e9matopo\u00ef\u00e9tiques peut entra\u00eener une cGVHD. <\/li>
- L’incidence estim\u00e9e est de 200 \u00e0 800 fois plus \u00e9lev\u00e9e chez les patients atteints d’AF que dans la population g\u00e9n\u00e9rale. R\u00e9cemment, les chercheurs se sont \u00e0 nouveau int\u00e9ress\u00e9s au d\u00e9veloppement des carcinome \u00e9pidermo\u00efde de la cavit\u00e9 buccale dans l’AF.<\/li>
- Dans une \u00e9tude rapportant des cas d’AF, l’\u00e2ge m\u00e9dian des 12 patients qui ont d\u00e9velopp\u00e9 des carcinomes buccaux apr\u00e8s une greffe de moelle osseuse \u00e9tait de 21 ans, ce qui \u00e9tait signi\ufb01cativement plus jeune que l’\u00e2ge de 28 ans pour les patients qui n’avaient pas re\u00e7u de greffe de moelle osseuse (P<\/li>
- Masserot et al. (2008) ont d\u00e9crit – la plus grande s\u00e9rie \u00e0 ce jour de carcinomes \u00e9pidermo\u00efdes de la t\u00eate et du cou – 13 patients (8 dans la cavit\u00e9 buccale) pr\u00e9sentant une an\u00e9mie de Fanconi apr\u00e8s une transplantation de cellules souches h\u00e9matopo\u00ef\u00e9tiques (HSCT). La survenue d’un carcinome \u00e9pidermo\u00efde de la langue chez une jeune personne qui ne fume pas devrait inciter \u00e0 consid\u00e9rer l’AF comme la condition m\u00e9dicale sous-jacente et conduire \u00e0 la r\u00e9alisation d’un test de d\u00e9pistage des cassures chromosomiques.<\/li><\/ul>\n
<\/div><\/div>\n\n
La Dyskeratose Congenitale<\/a><\/h3><\/p>\n\n\nDyskeratosis congenita (DC) is a rare multisystem inherited genodermatosis leading to reduced telemerase function impairing chromosomal stability. Also known as Zinsser-Cole-Engman syndrome, it was first described in 1906 . Telemeres form the ends of chromosomes and telemerase is an enzyme responsible for the synthesis of telomeres. A reduction in or impaired function of telemerase leads to a reduction in genetic material and subsequent activation of \u2018DNA damage response pathways\u2019 resulting in cell death. <\/p>\n\n\n\n
Bone marrow failure occurs as the bone marrow is dependent on telomere function due to its high cell turnover. In addition, DC also commonly manifests with mucocutaneous signs, pulmonary and\/or hepatic fibrosis.<\/p>\n\n\n\n
Aetiology<\/a><\/h3><\/div><\/div><\/p>\n\n\n\n- Dyskeratosis congenita is one of a few inherited marrow failure syndromes which has inheritance patterns including X-linked, autosomal dominant and autosomal recessive. <\/li>
- The specific genetic defect DKC1 mutation associated with X-linked DC, the most severe form of DC, leads to absence of functioning dyskerin, severely impairing telemerase function. <\/li>
- A number of genetic mutations have been identified resulting in different clinical manifestations including RTEL1 and TINF2 which have cerebellar hypoplasia and retinal disease as prominent features, respectively. <\/li>
- Recessive mutations in NOP10, CTC1, NHP2, PARN and WRAP53 are rarer and lead to differing clinical presentations. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Epidemiology<\/a><\/h3><\/p>\n\n\n\n- Dyskeratosis congenita is rare, typically presenting clinically between 5-12 years and has a male predominance. <\/li>
- An estimated incidence of 1 in 1000000 people has been reported. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Clinical Presentation<\/a><\/h3> <\/p>\n\n\n\n- The presentation of DC is typically early in life, in contrast to acquired forms of aplastic anaemia and are the consequence of the genetic mutations . <\/li>
- Zinsser in 1906 first described the characteristic triad of DC which includes the following:<\/li><\/ul>\n\n\n\n
- Reticular atrophy and cutaneous hyperpigmentation <\/li>
- Nail dystrophy (Figure 1)<\/li>
- Oral leukoplakia <\/li><\/ul>\n\n\n\n
- In patients with DC as a result of chromosomal instability, there is an increased risk of developing cancer affecting various bodily systems. <\/li>
- It has been reported that children with DC have a 100-fold increased risk of developing Acute Myeloid Leukaemia (AML). <\/li>
- There is also an increased risk of developing squamous cell carcinomas of the head and neck, cervix and anogenital region. <\/li>
- Cancers of the skin, aerodigestive tract and pancreas have also been reported and majority of all cancers occur in third decade of age. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Oral Manifestations<\/a><\/h3><\/p>\n\n\n\n- A number of intraoral changes have been reported to present in patients with DC including oral leukoplakia, which is the most common feature found in up to 80% of patients . <\/li>
- The most common sites involved are the tongue, buccal mucosa, palate and gingivae. <\/li>
- There can also be soft tissue changes including erythema, particularly in the buccal mucosa and tongue, brown pigmentation, and depapillation of the tongue. <\/li>
- In addition, altered sensation described as burning of the tongue has been reported <\/li><\/ul>\n\n\n\n
Dental Implications:<\/strong><\/em><\/p>\n\n\n\n- Gingival inflammation and periodontal disease are frequently seen in patients with DC due to a combination of early destruction of periodontal tissues as a result of anomalies in ectodermal derived structures, and a poor response to this secondary to neutropenia. <\/li>
- Dental caries is frequently identified in patients with DC with one study of 73 patients reporting \u2018extensive caries\u2019 in 13 patients and these findings have been supported elsewhere.<\/li>
- Other dental anomalies seen in patients with DC include hypodontia, short blunted roots, thinned enamel, taurodontism, decreased crown\/root ratio, hypocalcification and gingival recession. <\/li><\/ul>\n\n\n\n
Malignant Transformation:<\/strong><\/em><\/p>\n\n\n\n- The rate of malignant transformation of oral leukoplakia has been documented to range between 0.13-34% depending on multiple risk factors such as age, sex, homogeneity and size of the lesion. <\/li>
- In DC, the rate of progression of such lesions to cancer is approximately 30% between 10-30 years. <\/li>
- Moreover, in DC due to early telomere shortening, cancers have been reported to present earlier in patients as young as 5 years. Therefore, close surveillance is essential and frequently require biopsies. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Differential diagnosis<\/a><\/h3> <\/p>\n\n\n\nAplastic anaemia can be classified into two broad categories; acquired and inherited. The acquired causes include idiopathic, which is the most common cause, drug induced, viral, pregnancy and connective tissue diseases. Inherited causes include Fanconi anaemia, Shwachman- Diamond Syndrome and GATA2 syndrome. Though Fanconi anaemia remains the most common differential diagnosis. <\/p>\n\n\n\n
Differential diagnoses oral white lesions involve infective processes such as candidiasis and non-infective causes including oral lichen planus, lichenoid lesions, white sponge naevus, frictional keratosis and graft-versus-host disease GVHD. <\/p>\n\n\n
<\/div><\/div>\n\n\n\n
Diagnosis<\/a><\/h3><\/p>\n\n\n\n- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
- The diagnosis of DC can be confirmed by performing blood tests including full blood count (FBC) and reticulocyte count to establish if pancytopenia is present. <\/li>
- A bone marrow biopsy may reveal a hypocellular marrow. <\/li>
- Further investigations would include specialised tests such as genetic sequencing, measurement of telomere length by flow cytometry fluorescence in situ hybridisation (FISH) and computed tomography (CT) scans to determine if pulmonary and\/or hepatic involvement. <\/li>
- In the case of a positive family history, prenatal genetic diagnosis by chorionic villus sampling or preimplantation genetic diagnosis may be available.<\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Management<\/a><\/h3><\/p>\n\n\n\n- Multidisciplinary (MDT) approach is required in the care of patient\u2019s diagnosed with DC and the health care professionals involved will be governed by the bodily systems involved.<\/li>
- Haematologists will have a focal role as bone marrow failure is a primary cause of early morbidity and mortality. <\/li>
- Oral leukoplakia particularly in patients with DC has the potential to transform into oral cancer and therefore attentive surveillance is required. <\/li>
- A holistic approach in preventing and managing dental disease through optimised preventative advice and interventions are essential in improving quality of life for patients with DC. <\/li><\/ul>\n\n\n\n
\u00bb Non-Surgical Management<\/p>
<\/p>\n\n\n\nNon-Surgical Management<\/strong><\/p>\n\n\n\nNon-surgical management of oral leukoplakia with topical tretinoin 0.1% solution<\/strong> resulted in partial improvement in two siblings aged 10 and 15 years old. Chemotherapeutic agents such as bleomycin and cyclophosphamide<\/strong> have been reported to be effective but similar results have not shown to be consistent in improving oral leukoplakia. Another reported etretinate, a vitamin A derivative<\/strong>, was effective for oral leukoplakia in DC. <\/p>\n\n\n
\u00bb View less<\/p><\/div><\/div><\/p>\n\n\n\n
\u00bb Surgical Management<\/p>
<\/p>\n\n\n\nSurgical Management<\/strong><\/p>\n\n\n\nOral and maxillofacial surgeons may decide to surgically intervene if atypia or squamous cell carcinoma is detected. Resections of oral soft and hard tissue will often require reconstruction with prosthesis, therefore necessitating detailed planning with a prosthodontist to achieve a satisfactory functional and aesthetic result. <\/p>\n\n\n\n
- L’an\u00e9mie de Fanconi (AF) est un trouble multisyst\u00e9mique caract\u00e9ris\u00e9 par un spectre d’anomalies cong\u00e9nitales, une insuffisance progressive de la moelle osseuse et une pancytop\u00e9nie, une forte susceptibilit\u00e9 \u00e0 la leuc\u00e9mie my\u00e9lo\u00efde aigu\u00eb (LMA) et aux tumeurs solides. <\/li>
- L’AF est pr\u00e9sente dans le monde entier et touche 1 naissance sur 100 000 aux \u00c9tats-Unis. Elle est notamment plus fr\u00e9quente chez les Africains (environ 1 sur 22 000), estim\u00e9e \u00e0 1 sur 45 000 en Isra\u00ebl et la population gitane espagnole pr\u00e9senterait la plus forte pr\u00e9valence.<\/li><\/ul>\n\n
- L’AF est un syndrome cliniquement h\u00e9t\u00e9rog\u00e8ne d’insuffisance de la moelle osseuse, d’anomalies cong\u00e9nitales qui peuvent affecter tous les organes. <\/li>
- Les patients atteints d’AF peuvent souffrir de diverses malformations. Les anomalies cong\u00e9nitales comprennent des malformations du squelette (petite taille, microc\u00e9phalie ou pouce hypoplasique), des anomalies des organes (r\u00e9naux, ophtalmiques, auriculaires, cardiaques et g\u00e9nitaux) et des anomalies de la pigmentation de la peau, comme les taches caf\u00e9 au lait (tableau 1). <\/li>
- Jusqu’\u00e0 pr\u00e9sent, 23 g\u00e8nes ont \u00e9t\u00e9 impliqu\u00e9s dans l’AF caus\u00e9e par des mutations germinales dans un des multiples g\u00e8nes de l’AF (FANCA \u00e0 FANCV). Les mutations dans le g\u00e8ne FANCA sont les plus courantes et sont impliqu\u00e9es dans 60 \u00e0 65 % des cas signal\u00e9s. Toutes les mutations dans les g\u00e8nes de l’AF sont transmises de mani\u00e8re autosomique r\u00e9cessive, \u00e0 l’exception de FANCB et RAD51, qui sont transmises respectivement de mani\u00e8re li\u00e9e au chromosome X et de mani\u00e8re autosomique dominante. <\/li>
- Les prot\u00e9ines de l’AF interagissent dans une voie cellulaire commune et participent \u00e0 divers aspects de la r\u00e9paration de l’ADN, notamment la r\u00e9paration des liaisons transversales de l’ADN, la stabilisation g\u00e9nomique et la r\u00e9gulation des prot\u00e9ines en aval. Les d\u00e9fauts de l’une de ces prot\u00e9ines de l’AF entra\u00eenent une instabilit\u00e9 g\u00e9nomique, des m\u00e9canismes de r\u00e9paration de l’ADN d\u00e9fectueux et un risque accru de cancer. \n<\/li>
- Les patients atteints de FA pr\u00e9sentant un dysfonctionnement h\u00e9matopo\u00ef\u00e9tique doivent g\u00e9n\u00e9ralement subir une greffe de moelle osseuse ou une greffe de cellules souches h\u00e9matopo\u00ef\u00e9tiques , qui est l’option th\u00e9rapeutique privil\u00e9gi\u00e9e. <\/li>
- L’une des complications les plus courantes apr\u00e8s une greffe de cellules souches h\u00e9matopo\u00ef\u00e9tiques est le d\u00e9veloppement de la maladie chronique du greffon contre l’h\u00f4te (cGVHD), qui est \u00e9galement un facteur de risque pour le d\u00e9veloppement de cancers, en particulier le carcinome \u00e9pidermo\u00efde buccal. La cGVHD est d\u00e9sormais reconnue comme une l\u00e9sion \u00e0 potentiel malin <\/li>
- \u00c9tant donn\u00e9 le large \u00e9ventail d’anomalies cliniques, les patients atteints d’AF n\u00e9cessitent une \u00e9valuation compl\u00e8te au moment du diagnostic. <\/li>
- L’AF peut \u00eatre difficle \u00e0 diff\u00e9rencier d’autres syndromes g\u00e9n\u00e9tiques, ce qui complique son diagnostic. L’expressivit\u00e9 variable de l’AF rend le diagnostic pr\u00e9coce difficile dans certains cas. <\/li>
- Une description clinique d\u00e9taill\u00e9e des alt\u00e9rations les plus fr\u00e9quentes trouv\u00e9es dans les diff\u00e9rents organes est donn\u00e9e par Moreno et al (2021). <\/li>
- Le diagnostic de laboratoire est \u00e9tabli par la positivit\u00e9 du test de cassure chromosomique lors de l’exposition \u00e0 des agents de r\u00e9ticulation de l’ADN. <\/li>
- Les autres m\u00e9thodes de diagnostic utilis\u00e9es sont le western blotting, l’amplification par PCR multiplexe et le s\u00e9quen\u00e7age de nouvelle g\u00e9n\u00e9ration. <\/li>
- Une fois le diagnostic confirm\u00e9, une surveillance \u00e0 vie des patients atteints d’AF est n\u00e9cessaire pour assurer un diagnostic pr\u00e9coce du cancer. Le conseil g\u00e9n\u00e9tique est essentiel. <\/li><\/ul>\n\n
CARACT\u00c9RISTIQUES CLINIQUES DE L’AN\u00c9MIE DE FANCONI<\/strong>
(adapted from Nalepa and Clapp 2018) <\/p>\n\n<\/div>\n\n\n\n- Malformations cranofaciales<\/li>
- Retard de d\u00e9veloppement<\/li>
- Petite taille<\/li>
- Hypodontie, petites dents<\/li>
- Saignement buccal<\/li>
- Gencives gonfl\u00e9es<\/li>
- L’association VACTERL<\/li>
- Pouce ou radius anormal<\/li><\/ul>\n<\/div>\n\n\n\n\n
- Ost\u00e9oporose<\/li>
- Insuffisance m\u00e9dullaire progressive<\/li>
- Malformations cardiaques<\/li>
- Malformations g\u00e9nito-urinaires et gastro-intestinales<\/li>
- Ectopie ou dysplasie r\u00e9nale<\/li>
- Dysfonction endocrienienne<\/li>
- Diminution de la fertilit\u00e9<\/li><\/ul>\n<\/div>\n<\/div>\n\n
- Environ un quart des patients atteints d’AF qui d\u00e9veloppent des tumeurs solides ne sont diagnostiqu\u00e9s comme tels qu’apr\u00e8s la d\u00e9couverte de leur cancer. <\/li>
- Par cons\u00e9quent, l’AF doit \u00eatre envisag\u00e9e dans les tumeurs malignes \u00e0 apparition pr\u00e9coce. L’apparition pr\u00e9coce du cancer de la bouche, telle que d\u00e9crite dans plusieurs rapports de cas (cit\u00e9s ci-dessous), peut servir d’indication pour envisager le diagnostic de l’AF chez les jeunes patients qui d\u00e9veloppent un HNSCC en l’absence de facteurs de risque.<\/li>
- L’AF peut entra\u00eener une insuffisance de la moelle osseuse. La transplantation de cellules souches h\u00e9matopo\u00ef\u00e9tiques peut entra\u00eener une cGVHD. <\/li>
- L’incidence estim\u00e9e est de 200 \u00e0 800 fois plus \u00e9lev\u00e9e chez les patients atteints d’AF que dans la population g\u00e9n\u00e9rale. R\u00e9cemment, les chercheurs se sont \u00e0 nouveau int\u00e9ress\u00e9s au d\u00e9veloppement des carcinome \u00e9pidermo\u00efde de la cavit\u00e9 buccale dans l’AF.<\/li>
- Dans une \u00e9tude rapportant des cas d’AF, l’\u00e2ge m\u00e9dian des 12 patients qui ont d\u00e9velopp\u00e9 des carcinomes buccaux apr\u00e8s une greffe de moelle osseuse \u00e9tait de 21 ans, ce qui \u00e9tait signi\ufb01cativement plus jeune que l’\u00e2ge de 28 ans pour les patients qui n’avaient pas re\u00e7u de greffe de moelle osseuse (P<\/li>
- Masserot et al. (2008) ont d\u00e9crit – la plus grande s\u00e9rie \u00e0 ce jour de carcinomes \u00e9pidermo\u00efdes de la t\u00eate et du cou – 13 patients (8 dans la cavit\u00e9 buccale) pr\u00e9sentant une an\u00e9mie de Fanconi apr\u00e8s une transplantation de cellules souches h\u00e9matopo\u00ef\u00e9tiques (HSCT). La survenue d’un carcinome \u00e9pidermo\u00efde de la langue chez une jeune personne qui ne fume pas devrait inciter \u00e0 consid\u00e9rer l’AF comme la condition m\u00e9dicale sous-jacente et conduire \u00e0 la r\u00e9alisation d’un test de d\u00e9pistage des cassures chromosomiques.<\/li><\/ul>\n
<\/div><\/div>\n\n
La Dyskeratose Congenitale<\/a><\/h3>
<\/p>\n\n\nDyskeratosis congenita (DC) is a rare multisystem inherited genodermatosis leading to reduced telemerase function impairing chromosomal stability. Also known as Zinsser-Cole-Engman syndrome, it was first described in 1906 . Telemeres form the ends of chromosomes and telemerase is an enzyme responsible for the synthesis of telomeres. A reduction in or impaired function of telemerase leads to a reduction in genetic material and subsequent activation of \u2018DNA damage response pathways\u2019 resulting in cell death. <\/p>\n\n\n\n
Bone marrow failure occurs as the bone marrow is dependent on telomere function due to its high cell turnover. In addition, DC also commonly manifests with mucocutaneous signs, pulmonary and\/or hepatic fibrosis.<\/p>\n\n\n\n
Aetiology<\/a><\/h3>
<\/div><\/div><\/p>\n\n\n\n- Dyskeratosis congenita is one of a few inherited marrow failure syndromes which has inheritance patterns including X-linked, autosomal dominant and autosomal recessive. <\/li>
- The specific genetic defect DKC1 mutation associated with X-linked DC, the most severe form of DC, leads to absence of functioning dyskerin, severely impairing telemerase function. <\/li>
- A number of genetic mutations have been identified resulting in different clinical manifestations including RTEL1 and TINF2 which have cerebellar hypoplasia and retinal disease as prominent features, respectively. <\/li>
- Recessive mutations in NOP10, CTC1, NHP2, PARN and WRAP53 are rarer and lead to differing clinical presentations. <\/li><\/ul>\n\n\n
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Epidemiology<\/a><\/h3>
<\/p>\n\n\n\n- Dyskeratosis congenita is rare, typically presenting clinically between 5-12 years and has a male predominance. <\/li>
- An estimated incidence of 1 in 1000000 people has been reported. <\/li><\/ul>\n\n\n
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Clinical Presentation<\/a><\/h3>
<\/p>\n\n\n\n- The presentation of DC is typically early in life, in contrast to acquired forms of aplastic anaemia and are the consequence of the genetic mutations . <\/li>
- Zinsser in 1906 first described the characteristic triad of DC which includes the following:<\/li><\/ul>\n\n\n\n
- Reticular atrophy and cutaneous hyperpigmentation <\/li>
- Nail dystrophy (Figure 1)<\/li>
- Oral leukoplakia <\/li><\/ul>\n\n\n\n
- In patients with DC as a result of chromosomal instability, there is an increased risk of developing cancer affecting various bodily systems. <\/li>
- It has been reported that children with DC have a 100-fold increased risk of developing Acute Myeloid Leukaemia (AML). <\/li>
- There is also an increased risk of developing squamous cell carcinomas of the head and neck, cervix and anogenital region. <\/li>
- Cancers of the skin, aerodigestive tract and pancreas have also been reported and majority of all cancers occur in third decade of age. <\/li><\/ul>\n\n\n
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Oral Manifestations<\/a><\/h3>
<\/p>\n\n\n\n- A number of intraoral changes have been reported to present in patients with DC including oral leukoplakia, which is the most common feature found in up to 80% of patients . <\/li>
- The most common sites involved are the tongue, buccal mucosa, palate and gingivae. <\/li>
- There can also be soft tissue changes including erythema, particularly in the buccal mucosa and tongue, brown pigmentation, and depapillation of the tongue. <\/li>
- In addition, altered sensation described as burning of the tongue has been reported <\/li><\/ul>\n\n\n\n
Dental Implications:<\/strong><\/em><\/p>\n\n\n\n
- Gingival inflammation and periodontal disease are frequently seen in patients with DC due to a combination of early destruction of periodontal tissues as a result of anomalies in ectodermal derived structures, and a poor response to this secondary to neutropenia. <\/li>
- Dental caries is frequently identified in patients with DC with one study of 73 patients reporting \u2018extensive caries\u2019 in 13 patients and these findings have been supported elsewhere.<\/li>
- Other dental anomalies seen in patients with DC include hypodontia, short blunted roots, thinned enamel, taurodontism, decreased crown\/root ratio, hypocalcification and gingival recession. <\/li><\/ul>\n\n\n\n
Malignant Transformation:<\/strong><\/em><\/p>\n\n\n\n
- The rate of malignant transformation of oral leukoplakia has been documented to range between 0.13-34% depending on multiple risk factors such as age, sex, homogeneity and size of the lesion. <\/li>
- In DC, the rate of progression of such lesions to cancer is approximately 30% between 10-30 years. <\/li>
- Moreover, in DC due to early telomere shortening, cancers have been reported to present earlier in patients as young as 5 years. Therefore, close surveillance is essential and frequently require biopsies. <\/li><\/ul>\n\n\n
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Differential diagnosis<\/a><\/h3>
<\/p>\n\n\n\nAplastic anaemia can be classified into two broad categories; acquired and inherited. The acquired causes include idiopathic, which is the most common cause, drug induced, viral, pregnancy and connective tissue diseases. Inherited causes include Fanconi anaemia, Shwachman- Diamond Syndrome and GATA2 syndrome. Though Fanconi anaemia remains the most common differential diagnosis. <\/p>\n\n\n\n
Differential diagnoses oral white lesions involve infective processes such as candidiasis and non-infective causes including oral lichen planus, lichenoid lesions, white sponge naevus, frictional keratosis and graft-versus-host disease GVHD. <\/p>\n\n\n
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Diagnosis<\/a><\/h3>
<\/p>\n\n\n\n- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
- The diagnosis of DC can be confirmed by performing blood tests including full blood count (FBC) and reticulocyte count to establish if pancytopenia is present. <\/li>
- A bone marrow biopsy may reveal a hypocellular marrow. <\/li>
- Further investigations would include specialised tests such as genetic sequencing, measurement of telomere length by flow cytometry fluorescence in situ hybridisation (FISH) and computed tomography (CT) scans to determine if pulmonary and\/or hepatic involvement. <\/li>
- In the case of a positive family history, prenatal genetic diagnosis by chorionic villus sampling or preimplantation genetic diagnosis may be available.<\/li><\/ul>\n\n\n
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Management<\/a><\/h3>
<\/p>\n\n\n\n- Multidisciplinary (MDT) approach is required in the care of patient\u2019s diagnosed with DC and the health care professionals involved will be governed by the bodily systems involved.<\/li>
- Haematologists will have a focal role as bone marrow failure is a primary cause of early morbidity and mortality. <\/li>
- Oral leukoplakia particularly in patients with DC has the potential to transform into oral cancer and therefore attentive surveillance is required. <\/li>
- A holistic approach in preventing and managing dental disease through optimised preventative advice and interventions are essential in improving quality of life for patients with DC. <\/li><\/ul>\n\n\n\n
\u00bb Non-Surgical Management<\/p>
<\/p>\n\n\n\nNon-Surgical Management<\/strong><\/p>\n\n\n\n
Non-surgical management of oral leukoplakia with topical tretinoin 0.1% solution<\/strong> resulted in partial improvement in two siblings aged 10 and 15 years old. Chemotherapeutic agents such as bleomycin and cyclophosphamide<\/strong> have been reported to be effective but similar results have not shown to be consistent in improving oral leukoplakia. Another reported etretinate, a vitamin A derivative<\/strong>, was effective for oral leukoplakia in DC. <\/p>\n\n\n
\u00bb View less<\/p><\/div><\/div><\/p>\n\n\n\n
\u00bb Surgical Management<\/p>
<\/p>\n\n\n\nSurgical Management<\/strong><\/p>\n\n\n\n
Oral and maxillofacial surgeons may decide to surgically intervene if atypia or squamous cell carcinoma is detected. Resections of oral soft and hard tissue will often require reconstruction with prosthesis, therefore necessitating detailed planning with a prosthodontist to achieve a satisfactory functional and aesthetic result. <\/p>\n\n\n\n
- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
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