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PURPOSE: To evaluate the oral health-related quality of life (OHRQoL) of individuals diagnosed with Fanconi anemia (FA). METHODS: A cross-sectional study was conducted with FA patients from two Brazilian referral centers. Participants underwent a complete dental, periodontal, and oral mucosa examination, as well as assessment of resting salivary flow. The short version of the Oral Health Impact Profile (OHIP-14) questionnaire was administered. Descriptive and bivariate analyses were performed, followed by multivariate analysis to examine the impact of independent variables on OHRQoL. RESULTS: The study included 20 (57.1%) males and 15 (42.9%) females, with a mean age of 18.9 years. Oral leukoplakia (OL) was found in 18 individuals. The overall OHIP-14 score was 9.9 ± 10.5. Individuals aged ≥ 16 years had higher OHIP-14 scores, indicating worse OHRQoL for physical pain (p = 0.007), psychological discomfort (p = 0.001), physical disability (p = 0.03), psychological disability (p = 0.001), handicap (p = 0.004), and overall score (p = 0.007). Females reported more negative OHRQoL than males for physical pain (p = 0.02), psychological discomfort (p = 0.03), psychological disability (p = 0.009), and overall score (p = 0.02). Individuals with OL had an overall OHIP-14 score 1.83 times higher than those without OL (95% CI: 1.02-3.28; p = 0.04). Lower salivary flow correlated with higher overall OHIP-14 scores (95% CI: 0.14-0.84; p = 0.01). CONCLUSION: This study represents the first attempt to evaluate OHRQoL in individuals with FA. The presence of OL and reduced salivary flow were identified as predictors of a negative impact on OHRQoL. It is imperative to integrate patients' quality of life in the clinical treatment protocols for the FA population.

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INTRODUCTION: Fanconi anemia (FA) is a recessive hereditary disease characterized by bone marrow failure, and the treatment is hematopoietic stem cell transplantation (HSCT). Patients diagnosed with FA are more predisposed to develop oral squamous cell carcinoma (SCC), and this risk increases in transplant patients. The clinical characteristics of the oral manifestations of SCC in this group of patients do not differ from the lesions present in patients without the disease; however, they can be diagnosed in young patients and less common locations, such as, for example, in the buccal mucosa. OBJECTIVE: To report a case series of patients diagnosed with FA with oral SCC. METHOD: Included in this case series are six patients diagnosed with SCC in the buccal mucosa with similar clinical characteristics. FINAL CONSIDERATIONS: There are still difficulties in establishing the natural history of oral lesions in patients with FA. Thus, disclosing a series of cases with similar changes may be relevant to improving and refining the multidisciplinary team's clinical view of suspected SCC or oral potentially malignant disorders (OPMD), providing surveillance and timely management.

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O presente estudo teve por objetivo avaliar a qualidade de vida relacionada a saúde bucal (QVRSB) de indivíduos com Anemia de Fanconi (AF) e sua associação com alterações bucais. O estudo avaliou de forma transversal 35 indivíduos diagnósticados com AF em dois centros de referência no Brasil: HC-UFMG (n=13) e HC-UFPR (n=22). Os participantes foram submetidos a exame completo dentário, periodontal e da mucosa oral, além de avaliação do fluxo salivar não estimulado. A versão curta do questionário Oral Health Impact Profile (OHIP-14) foi aplicada. A média de idade dos indivíduos foi 18 anos (variação: 7-42 anos) e 57,1% eram do sexo masculino. A maior parte dos pacientes (68,6%) foram submetidos ao transplante hematopoiético de células tronco (THCT) e apresentavam alterações esqueléticas unilateral em membros superiores (60%). Em cavidade bucal, as principais alterações foram desordens orais potencialmente malignas (DOPM) (51,4%), dentes cariados (57,2%), gengivite (37,1%) e higiene bucal precária. A mediana da pontuação geral do OHIP-14 foi de 6,0 (variação: 0­47), com pontuações mais altas observadas nos domínios dor física e desconforto psicológico. Indivíduos do sexo feminino apresentaram uma pontuação geral no OHIP-14 1,95 vezes maior, embora não significativamente estatístico, em comparação aos indivíduos do sexo masculino (IC 95%: 0,99­3,84; p=0,05). Indivíduos com DOPM apresentaram uma pontuação geral no OHIP-14 1,83 vezes maior do que aqueles sem DOPM (IC 95%: 1,02­3,28; p=0,04), enquanto o menor fluxo salivar foi associado com maiores pontuações gerais no OHIP-14 (IC 95%: 0,14­0,84; p=0,01). Em conjunto, os dados deste trabalho apontam a necessidade de vigilância rigorosa de pacientes com AF, mesmo na ausência de DOPM, para detecção precoce de CCEO e redução da mortalidade, além da importância de priorizar a qualidade de vida dos pacientes na implementação de protocolos clínicos de tratamento na população com AF.

The present study aims to evaluate the oral health-related quality of life (OHRQoL) of individuals with Fanconi Anemia (FA) and its association with oral changes. The study cross-sectionally evaluated 35 individuals diagnosed with FA in two referral centers in Brazil: HC-UFMG (n=13) and HC-UFPR (n=22). Participants underwent a complete dental, periodontal and oral mucosa examination, in addition to evaluation of unstimulated salivary flow. The short version of the Oral Health Impact Profile questionnaire (OHIP-14) was administered. The average age of the individuals was 18 years (range: 7-42 years) and 57.1% were male. Most patients (68.6%) underwent hematopoietic stem cell transplantation (HSCT) and presented unilateral skeletal changes in the upper limbs (60%). In the oral cavity, the main changes were malignant environmental oral disorders (OPMD) (51.4%), decayed teeth (57.2%), gingivitis (37.1%) and poor oral hygiene. The median overall OHIP-14 rating was 6.0 (range: 0­ 47), with higher scores observed in the domains of physical pain and psychological discomfort. Individuals without oral loss presented as OPMD were 0.54 times more likely to have obtained lower overall scores on the OHIP-14 (95% CI: 0.30­0.97; p=0.04). Individuals with low salivary flow had higher overall OHIP-14 results (95% CI: 0.14­0.84; p=0.01). Female individuals with OPMD and reduced salivary flow were more likely to experience a negative impact on OHRQoL. Furthermore, these individuals had high rates of oral changes and poor oral hygiene. Taken together, the data from this work point to the need for rigorous surveillance of patients with FA, even in the absence of OPMD, for early detection of OSCC and reduction of mortality, in addition to the importance of prioritizing patients' quality of life when implementing protocols treatment clinics in the FA population.

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Este estudo objetivou realizar uma revisão sistemática da literatura (RSL) sobre anomalias dentárias e craniofaciais em indivíduos com Anemia de Fanconi (AF), além de avaliar a ocorrência dessas alterações em um estudo transversal aprovado pelo Comitê de Ética em Pesquisa. A pesquisa foi realizada em parceria com o Hospital das Clínicas da Universidade Federal de Minas Gerais e o Hospital de Clínicas da Universidade Federal do Paraná, dois centros de referência no Brasil. A AF é uma doença genética rara e carece de estudos sobre características dentárias e craniofaciais. Para a RSL, foram realizadas buscas eletrônicas em seis bases de dados, complementadas por análise manual e da literatura cinzenta. Foram incluídos estudos transversais e relatos de casos. No total, 19 artigos com 158 casos de AF foram analisados. A prevalência estimada de anomalias dentárias variou de 13,3% a 71,4%. Dos 158 indivíduos, 130 apresentavam anormalidades dentárias e/ou radiculares, e 56 tinham maloclusão e/ou anomalias craniofaciais. O estudo transversal foi baseado em avaliação clínico-radiográfica e incluiu 46 pacientes diagnosticados com AF a partir de exames de pesquisa de quebras cromossômicas. Nosso estudo revelou que 93,5% dos pacientes apresentaram anomalias dentárias e/ou craniofaciais, especialmente anormalidades radiculares. Homens apresentaram predominantemente anomalias de erupção/exfoliação. Uma maior ocorrência de anomalias relacionadas ao tamanho do dente foi observada em indivíduos que passaram por transplante de células-tronco hematopoéticas com idade ≥14 anos. A literatura limitada e a variabilidade de anomalias dentárias e craniofaciais na AF destacam a necessidade de expandir e padronizar critérios de diagnóstico e o monitoramento destes indivíduos, o que pode ajudar a mitigar o impacto dessa condição na saúde geral e qualidade de vida dos indivíduos afetados.

The present study aimed to conduct a systematic review of the literature on dental and craniofacial anomalies in individuals with Fanconi Anemia, as well as to evaluate the occurrence of these alterations in a cross-sectional study approved by the Research Ethics Committee. The research was conducted in partnership with two Brazilian reference centers, the Hospital das Clínicas of the Federal University of Minas Gerais and the Hospital de Clínicas of the Federal University of Paraná. Fanconi Anemia (FA) is a rare genetic disease and lacks studies on dental and craniofacial characteristics. For the systematic literature review, electronic searches were conducted in six databases, complemented by manual analysis and gray literature. Cross-sectional studies and case reports were included. A total of 19 articles describing 158 cases of FA were analyzed. The estimated prevalence of dental anomalies ranged from 13.3% to 71.4%. Among the 158 individuals, 130 exhibited dental and/or root abnormalities, while 56 presented malocclusion and/or craniofacial anomalies. Our cross-sectional study was based on clinical-radiographic evaluation and included 46 patients diagnosed with FA through chromosomal breakage tests and/or genetic tests. Our study revealed that 93.5% of the patients presented dental and/or craniofacial anomalies, particularly root abnormalities. that 93.5% of patients presented dental/craniofacial anomalies, particularly radicular abnormalities. Males predominantly exhibited eruption/exfoliation anomalies. A higher occurrence of anomalies related to tooth size was observed in individuals who underwent hematopoietic stem cell transplantation at ≥14 years of age. The limited literature and variability of dental and craniofacial anomalies in FA highlight the need to expand and standardize diagnostic criteria for effective monitoring and mitigation of their impact on health and quality of life.

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ABSTRACT Introduction: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. Method: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. Results: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. Conclusions: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

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INTRODUCTION: Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosomal instability and increased predisposition to malignancy. The diagnosis of FA requires clinical evaluation, confirmation of chromosomal fragility and/or analysis of genetic mutations. Therefore, this study aims to identify the clinical profile of patients with FA in the state of Pernambuco, Brazil. METHOD: We analyzed 100 individuals referred from the major hematology and bone marrow (BM) transplant centers in the state of Pernambuco, Brazil, between the years 2018 and 2022. The diagnosis of FA was performed using the mitomycin C chromosomal fragility test, clinical data and classical and molecular cytogenetic analyses. RESULTS: We enrolled a total of 16 patients with FA to comprise this study. Most of these individuals (87.5%) came from the Agreste and Sertão regions of Pernambuco. We observed a slight female prevalence of FA (1.3:1). The primary clinical and laboratory findings were café au lait spots (62.5%) and bone abnormalities (53%, mainly thumb deformities [40%]). We performed BM cytogenetic analysis for eight patients - seven showed no chromosomal abnormalities and one presented the karyotype 47,XY,+21 [15]. CONCLUSIONS: Our results are important to promote public health measures for the early diagnosis of FA, as well as to foster the engagement of a multidisciplinary group in the treatment of this disease.

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INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

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INTRODUCTION: This study proposed to identify Fanconi anemia (FA) mutations in Brazilian patients and to investigate their impact on clinical manifestations and malignancies onset. METHODS: A total of 116 patients were screened for nine mutations in FANCA, FANCC, FANCG. Those with no mutations were investigated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing for FANCA, FANCC, FANCE, FANCF, FANCG, FANCD1/BRCA2. RESULTS: Genetic subtype was identified in 107/116 (78 FA-A, 8 FA-C, 13 FA-G, 8 FA-E), with only one mutation in 1/116, and no mutations in 9/116 patients. Before hematopoietic cell transplantation (HCT), malignancies were detected in 16/116 patients (14/78 FA-A, 01/08 FA-C, 01/08 FA-E), and 12 of them were hematological. Observed to expected ratio (O/E) of hematologic malignancy was 303.7 (95% CI = 148.6-458.7). CONCLUSION: This study allowed the identification of biallelic mutations in 91.4% of patients. FANCG and FANCC mutations had significantly earlier bone marrow failure onset, and FANCG severe cytopenia at diagnosis. Despite the inherent limitations of the small number of malignancy events in each genetic subtype, the hematologic malignancies O/E ratio was very high. Cumulative incidence of malignancy before HCT was higher in the third and fourth decades of life, considering HCT and death as competing risks. The cumulative incidence of HCT increased during the first decade, competing with malignancy development.

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ABSTRACT Objective: The aim of this study was to elaborate a specific protocol for the assessment and early identification of skin lesions in pediatric patients with Fanconi anemia undergoing hematopoietic stem cell transplantation. Methods: This is a longitudinal, retrospective, and descriptive study. The medical records of 136 pediatric patients with Fanconi anemia who underwent hematopoietic stem cell transplantation between 2008 and 2018 at the Clinical Hospital of the Federal University of Paraná were reviewed. A specific protocol was created for data collection, which included age, sex, skin color, age at diagnosis of Fanconi anemia, transplantation data, family history of consanguinity, and pre- and post-transplant complications. In addition, the data included the presence of graft-versus-host disease of the skin and other organs, its classification, type of lesion, location, and also skin lesions not related to graft-versus-host disease. Results: Among the skin manifestations in pre-transplant period, café-au-lait spots stood out (32.4%). At least one organ was affected by graft-versus-host disease in 55.1% of patients; the most common involvement being the mouth, followed by the skin. Rash and erythema were the most frequently observed cutaneous manifestations of graft-versus-host disease. Conclusion: A high prevalence of cutaneous manifestations of the disease was observed, as well as cutaneous manifestations of graft-versus-host disease. The protocol developed gathers relevant and standardized information for the follow-up of patients with Fanconi anemia undergoing hematopoietic stem cell transplantation, ensuring greater reliability of the information, and its implementation will allow the prospective evaluation of patients.

RESUMO Objetivo: Elaborar um protocolo específico para a avaliação e identificação precoces de lesões de pele em pacientes pediátricos com anemia falciforme submetidos ao transplante de células-tronco hematopoiéticas. Métodos: Estudo longitudinal, retrospectivo e descritivo. Foram revisados os prontuários dos pacientes pediátricos com anemia de Fanconi submetidos a transplante de células-tronco hematopoiéticas entre os anos de 2008 e 2018 no Hospital de Clínicas da Universidade Federal do Paraná, totalizando 136 pacientes. Foi criado um protocolo específico para a coleta de dados, que incluiu: idade, sexo, cor, idade ao diagnóstico da anemia de Fanconi, dados do transplante, história familiar de consanguinidade e complicações pré e pós-transplante. Além disso, foram verificados a presença de doença do enxerto contra o hospedeiro da pele e de outros órgãos, sua classificação, tipo de lesão, localização e, também, lesões de pele não relacionadas à doença. Resultados: Entre as manifestações de pele no período pré-transplante, destacaram-se as manchas café com leite (32,4%). Pelo menos um órgão foi afetado pela doença do enxerto contra o hospedeiro em 55,1% dos pacientes, sendo o acometimento mais comum o de boca, seguido pelo de pele. Exantema e eritema foram as manifestações cutâneas mais frequentemente observadas. Conclusões: Observou-se alta prevalência de manifestações cutâneas próprias da doença, bem como de manifestações cutâneas de doença do enxerto contra o hospedeiro. O protocolo elaborado reúne informações relevantes e padronizadas para o acompanhamento dos pacientes com anemia de Fanconi submetidos ao transplante, garantindo maior confiabilidade das informações, e sua implementação permitirá a avaliação prospectiva dos pacientes.

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Abstract Fanconi anemia is a rare autosomal recessive disease. In this disease, cytokine pathways can induce the bone marrow failure that is observed in individuals with Fanconi anemia. Interleukin IL-17 exhibits a protective effect in organisms because it induces neutrophil recruitment and shows a pathological role in several models of autoimmune diseases, periodontal disease, cancer, allograft rejection, and graft versus host disease. Polymorphisms in the IL17A and IL17RA genes were evaluated from DNA in saliva, comparing individuals with or without Fanconi anemia, using models of genotypic transmission (additive, dominant, and recessive). Polymorphisms in the IL17A and IL17RA genes (rs2241044 [C allele], rs879577 [C allele], rs9606615 [T allele], and rs2241043 [C allele]) were risk factors for developing Fanconi anemia. We also performed an analysis of gene markers with clinical variables in the Fanconi group. Polymorphisms in the IL17A gene (rs3819025 [A allele] and rs2275913 [G allele], respectively) were associated with an age of less than 20 years (p = 0.026; RP 0.65) and the female sex (p = 0.043; RP 0.88). The IL17RA gene was also associated with age and the presence of leukoplakia (a potentially malignant oral disorder). An age of less than 20 years was associated with rs917864 (T allele; p = 0.036; RP 0.67). The presence of leukoplakia was associated with rs17606615 (T allele; p = 0.042; RP 0.47). To our knowledge, this is the first study that associates IL17A and IL17RA gene polymorphisms with Fanconi anemia and examines rs2241044 polymorphisms in scientific literature thus far.

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Fanconi Anemia (FA) is a disease characterized by genomic instability, increased sensitivity to DNA cross-linking agents, and the presence of clonal chromosomal abnormalities. This genomic instability can compromise the bone marrow (BM) and confer a high cancer risk to the patients, particularly in the development of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). The diagnosis of FA patients is complex and cannot be based only on clinical features at presentation. The gold standard diagnostic assay for these patients is cytogenetic analysis, revealing chromosomal breaks induced by DNA cross-linking agents. Clonal chromosome abnormalities, such as the ones involving chromosomes 1q, 3q, and 7, are also common features in FA patients and are associated with progressive BM failure and/or a pre-leukemia condition. In this review, we discuss the cytogenetic methods and their application in diagnosis, stratification of the patients into distinct prognostic groups, and the clinical follow-up of FA patients. These methods have been invaluable for the understanding of FA pathogenesis and identifying novel disease biomarkers. Additional evidence is required to determine the association of these biomarkers with prognosis and cancer risk, and their potential as druggable targets for FA therapy.

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Inherited bone marrow failure syndromes (IBMFS) are a complex and heterogeneous group of genetic diseases. To date, at least 13 IBMFS have been characterized. Their pathophysiology is associated with germline pathogenic variants in genes that affect hematopoiesis. A couple of these diseases also have genomic instability, Fanconi anemia due to DNA damage repair deficiency and dyskeratosis congenita/telomere biology disorders as a result of an alteration in telomere maintenance. Patients can have extramedullary manifestations, including cancer and functional or structural physical abnormalities. Furthermore, the phenotypic spectrum varies from cryptic features to patients with significantly evident manifestations. These diseases require a high index of suspicion and should be considered in any patient with abnormal hematopoiesis, even if extramedullary manifestations are not evident. This review describes the disrupted cellular processes that lead to the affected maintenance of the genome structure, contrasting the dysmorphological and oncological phenotypes of Fanconi anemia and dyskeratosis congenita/telomere biology disorders. Through a dysmorphological analysis, we describe the phenotypic features that allow to make the differential diagnosis and the early identification of patients, even before the onset of hematological or oncological manifestations. From the oncological perspective, we analyzed the spectrum and risks of cancers in patients and carriers.

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BACKGROUND: Fanconi anemia is a congenital disorder belonging to bone marrow syndromes, with a risk of developing malignancy. Hematopoietic stem cell transplantation is the only curative treatment in these cases. Here, we aimed to report our clinical experience in pediatric patients with Fanconi anemia treated with haploidentical stem cell transplantation and post-transplant cyclophosphamide, an alternative strategy. METHODS: We performed a case report based on clinical records of two patients who signed the informed consent form and were treated at Fundación Valle del Lili. RESULT: Two pediatric patients, both with reduced-intensity conditioning, prophylaxis for acute graft-versus-host disease with post-transplant cyclophosphamide. They achieved primary neutrophil/platelets engraftment, and 100% chimerism. Had grade I or II graft-versus-host disease resolved? Currently are alive and in complete remission. CONCLUSIONS: The use of mismatched related donors for haploidentical stem cell transplantation and post-transplant cyclophosphamide might be a promising option, and well-tolerated in pediatric patients. Serial chimerism can be useful during follow-up.

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INTRODUCTION: Fanconi anaemia (FA) is a rare genetic disorder marked by progressive bone marrow failure, chromosomal fragility, and increased cancer susceptibility. Laboratory diagnosis includes chromosomal instability test and mutation investigation. A total of 15%-25% of all patients may have somatic mosaicism, characterized by two distinct haematopoietic cell populations, one resistant and one sensitive to agents that induce chromosomal breakage, which complicates the diagnosis by a high incidence of reverted cells leading to inconclusive or false-negative results. The study aimed to evaluate the use of bone marrow stromal mesenchymal cells (BM-MSCs) as an alternative, non-haematopoietic tissue for diagnosis. METHODS: Bone marrow mesenchymal stromal cells from 12 patients with positive diepoxybutane (DEB) tests were cultivated and analysed by cytogenetics and mutation investigation. RESULTS: The DEB test was performed at 0.1 and 0.01 µg/ml concentrations, with an index ranging from 0.24 to 1.00. At higher concentration, the metaphases number was lower, probably due to toxicity. Regarding the molecular investigation, all the mutations previously found in peripheral blood were identified on BM-MSC. CONCLUSION: This study demonstrated the possibility of using BM-MSCs as an alternative tissue for cytogenetic and molecular investigation. Future tests using an intermediate DEB concentration may lead to an optimal protocol that could be non-toxic to cells but provides conclusive results.

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Fanconi anemia (FA) is a rare genetic disorder caused by pathogenic variants (PV) in at least 22 genes, which cooperate in the Fanconi anemia/Breast Cancer (FA/BRCA) pathway to maintain genome stability. PV in FANCA, FANCC, and FANCG account for most cases (~90%). This study evaluated the chromosomal, molecular, and physical phenotypic findings of a novel founder FANCG PV, identified in three patients with FA from the Mixe community of Oaxaca, Mexico. All patients presented chromosomal instability and a homozygous PV, FANCG: c.511-3_511-2delCA, identified by next-generation sequencing analysis. Bioinformatic predictions suggest that this deletion disrupts a splice acceptor site promoting the exon 5 skipping. Analysis of Cytoscan 750 K arrays for haplotyping and global ancestry supported the Mexican origin and founder effect of the variant, reaffirming the high frequency of founder PV in FANCG. The degree of bone marrow failure and physical findings (described through the acronyms VACTERL-H and PHENOS) were used to depict the phenotype of the patients. Despite having a similar frequency of chromosomal aberrations and genetic constitution, the phenotype showed a wide spectrum of severity. The identification of a founder PV could help for a systematic and accurate genetic screening of patients with FA suspicion in this population.

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Fanconi anemia (FA) is a rare disease characterized by progressive bone marrow failure, cancer predisposition, and multiple systemic malformations, including congenital abnormalities of the kidney and urinary tract (CAKUT). Hematopoietic cell transplantation (HCT), the only potentially curative treatment for the hematological complications of FA, may precipitate acute kidney injury (AKI) and hypertension. We retrospectively investigated 107 FA patients who underwent HCT between 2009 and 2017. We investigated the incidence and risk factors of AKI within 100 days after HCT in a cohort of FA patients, and kidney function and hypertension over 2-year follow-up.The incidence of AKI (mainly stage I) was 18.7%. Patients aged ≥ 11 years at transplantation showed a higher risk of AKI (OR 3.53). The eGFR was 60-90 mL/min/1.73 m2 in 53 (49.5%), 55 (51.4%), 50 (50.5%), 50 (51%), and 46 (59.7%) patients before HCT, at 100 days, 6 months, 1 year, and 2 years. Within the first 100 days after HCT, hypertension was observed in 72% of the patients and was associated with cyclosporine therapy. Most (62.3%) patients had stage 2 hypertension. CAKUT was observed in 33.7% of the patients and was associated with both hypertension (86%) and diminished kidney function but not with AKI.Conlusion: Although AKI, a commonly known HCT complication, was mild in this study, the prevalence of chronic kidney disease (CKD), as well as the high incidence of hypertension, specially associated with CAKUT point out the importance of kidney care in short and long-term follow up of FA patients. What is Known: • Fanconi anemia (FA) is the most frequent inherited bone marrow failure in children, and 30% of cases have congenital anomalies of kidney (CAKUT). • Acute kidney injury and hypertension after hematopoietic cell transplantation (HCT) may impact the outcomes.. What is New: • Despite the presence of CAKUT and stage 2 CKD in 33.7% and 50% of the patients, respectively, AKI was mild and transitory after HCT in FA patients. • CAKUT in FA patients was associated with lower kidney function and hypertension after HCT.

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Fanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer. Currently, hematopoietic stem cell transplant (HSCT) is the only curative treatment available for bone marrow failure; however, HSCT increases oral squamous cell carcinoma (OSCC) risk. Here we report the case of a patient diagnosed with Fanconi anemia in childhood who was treated with HSCT and later diagnosed with multiple OSCCs during a 12-year follow-up. Despite multiple surgical interventions and radiotherapy regimens, the patient`s health deteriorated. Management of individuals with Fanconi anemia is challenging and must be provided by a multidisciplinary healthcare team to ensure better staging, treatment planning, and coordination.

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OBJECTIVES: To describe the prevalence of acquired ocular manifestations in patients with Fanconi anemia (FA) and to describe and correlate the congenital ocular malformations with the genetic subtypes of the disease. STUDY DESIGN: This is a cross-sectional observational study of 106 consecutive patients with confirmed diagnosis of FA who were followed at the Hematopoietic Stem Cell Transplantation (HSCT) Service at the Federal University of Paraná, Curitiba, Parana, Brazil. Participants underwent a complete ophthalmologic evaluation and 84 patients underwent ocular ultrasound examination. This study was conducted between November 2014 and August 2017. RESULTS: The patients ranged in age from 6 months to 43 years of age. Microphthalmia was the most common congenital ocular abnormality (95.2%). A decrease in anthropometric measurements was observed, including palpebral fissure length (78/103 patients [76.5%]), microcornea (48/103 patients [46.6%]), and ptosis (31/103 patients [30.1%]). We identified a new ophthalmic condition in 15 patients with FA, that is, epiretinal tissue on the optic disc. The genetic subtype was identified in 78 patients (79.6%), the FA-A subtype was most prevalent (50%). The most common acquired ocular manifestation (non-graft-versus-host disease [GVHD] related) in patients who did not undergo HSCT (n = 44) was limbal neovascularization (13.6%), whereas in patients who underwent HSCT (n = 62), the GVHD-related manifestation was ocular GVHD (51.6%). The most frequent symptom of ocular GVHD was keratoconjunctivitis sicca (29%). CONCLUSIONS: Several ocular manifestations were identified in patients with FA.

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INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with Fanconi anemia (FA) and hematological manifestations but it does not prevent solid tumors, especially squamous cell carcinomas (SCC). METHODS: Retrospective study in 22 FA patients who had received HSCT and had been followed up beyond 2 years after HSCT. RESULTS: The median follow-up was 15 years. Six patients developed head-and-neck SCC after transplantation. The cumulative incidence of SCC at 15 and 30 years from the HSCT was 14.2% and 71.2%, respectively. One patient was diagnosed in stage IV and the rest, who were being followed up in cancer screening programs, in stage I. Treatment of SCC consisted of surgery in all patients; radiotherapy and chemotherapy were used in two patients and were poorly tolerated. CONCLUSION: FA patients have high risk of head-and-neck SCC. Multi-disciplinary programs for early cancer detection are of special relevance in these patients.

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ABSTRACT Objectives: to identify nursing diagnoses in patients who underwent hematopoietic stem-cell transplants due to Fanconi anemia, according to the NANDA-I taxonomy. Methods: exploratory study using a retrospective analysis of 85 records from patients who underwent hematopoietic stem-cell transplants due to Fanconi anemia, developed in a specialize transplant center in the South of Brazil. The results were analyzed using descriptive statistics. Results: 73 different diagnoses were found in 9 out of the 13 domains from the NANDA-I taxonomy. From these, 22 were in 50% or more of the patients investigated, and most of them are related to the domain Safety/Protection. Conclusions: it was possible to identify the nursing diagnosis in the patients who underwent hematopoietic stem cell transplants due to Fanconi anemia, contributing to design a plan for the care of these patients. The same was true for those with other syndromes of chromosomal instability that need to undergo this transplant.

RESUMEN Objetivos: identificar diagnósticos de enfermería en pacientes sometidos a trasplante de células madre hematopoyéticas por anemia de Fanconi, segundo la taxonomía NANDA-I. Métodos: estudio exploratorio mediante análisis retrospectivo de registros de 85 prontuarios de pacientes sometidos a trasplante de células madre hematopoyéticas por anemia de Fanconi, desarrollado en un centro trasplantador de referencia del Sur Brasileño. Analizados los datos utilizándose estadística descriptiva. Resultados: identificaron 73 diferentes diagnósticos en 9 de los 13 dominios de la taxonomía NANDA-I. De estos, 22 diagnósticos atingieron 50% o más de los pacientes investigados, y el mayor número está relacionado al dominio de Seguridad y Protección. Conclusiones: fue posible identificar los diagnósticos de enfermería presentes en pacientes sometidos a un trasplante de células madre hematopoyéticas por anemia de Fanconi, contribuyendo para el delineamento del plan de cuidados de esos pacientes, incluso para aquellos con otros síndromes de inestabilidad cromosómica que necesitan ser sometidos al trasplante.

RESUMO Objetivos: identificar diagnósticos de enfermagem em pacientes submetidos a transplante de células-tronco hematopoéticas por anemia de Fanconi, segundo a taxonomia da NANDA-I. Métodos: estudo exploratório mediante análise retrospectiva dos registros de 85 prontuários de pacientes submetidos a transplante de células-tronco hematopoéticas por anemia de Fanconi, desenvolvido em um centro transplantador de referência do Sul do Brasil. Analisaram-se os dados utilizando-se estatística descritiva. Resultados: identificaram-se 73 diferentes diagnósticos em 9 dos 13 domínios da taxonomia da NANDA-I. Destes, 22 diagnósticos atingiram 50% ou mais dos pacientes investigados, e o maior número está relacionado ao domínio de Segurança e Proteção. Conclusões: foi possível identificar os diagnósticos de enfermagem presentes em pacientes submetidos a um transplante de células-tronco hematopoéticas por anemia de Fanconi, contribuindo para o delineamento do plano de cuidados desses pacientes, assim como para aqueles com outras síndromes de instabilidade cromossômica que necessitam ser submetidos ao transplante.