Ocular Manifestations in Patients with Fanconi Anemia: A Single-Center Experience Including 106 Patients

Graf, Christie Michelle; Nichele, Samantha; Siviero, Renata Bigolin; Loth, Gisele; Trennepohl, Joanna; Zinher, Mariana Tosato; Grandinetti, Alexandre Achille; Pilonetto, Daniela; Pasqüini, Ricardo; Moreira, Ana Tereza Ramos; Bonfim, Carmem

doi:10.1016/j.jpeds.2021.11.013

Cited by 6 publications

(7 citation statements)

References 29 publications

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“…Small eyes are described in 11% of patients with FA regardless of genotype [38], this feature stands for the "E" in the PHENOS acronym. However, the ocular phenotype in FA is wider as recently demonstrated [39] and broadening the features that conform the "E" in PHENOS should be considered.…”

Section: Discussionmentioning

confidence: 97%

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Reyes

Teresa

Juárez

et al. 2022

IJMS

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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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Section: Discussionmentioning

confidence: 97%

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Reyes

Teresa

Juárez

et al. 2022

IJMS

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“…For example, patients with iron deficiency anemia (IDA) were reported to have significantly thinner peripapillary retinal nerve fiber layer (RNFL) thickness, and the Hgb levels were also significantly correlated with the average RNFL thickness value ( Türkyilmaz et al, 2013 ; Akdogan et al, 2015 ). Additionally, optic atrophy, disc edema, and epiretinal tissue on the optic disc have been identified in anemia patients ( Sethi et al, 2020 ; Ab Gani et al, 2021 ; Graf et al, 2021 ), which suggested that the optic disc was susceptible to be affected by anemia. Moreover, ASModel_UWF paid attention to the peripheral retina.…”

Section: Discussionmentioning

confidence: 99%

Deep-Learning-Based Hemoglobin Concentration Prediction and Anemia Screening Using Ultra-Wide Field Fundus Images

Zhao

Meng

Su³

et al. 2022

Front. Cell Dev. Biol.

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Background: Anemia is the most common hematological disorder. The purpose of this study was to establish and validate a deep-learning model to predict Hgb concentrations and screen anemia using ultra-wide-field (UWF) fundus images.Methods: The study was conducted at Peking Union Medical College Hospital. Optos color images taken between January 2017 and June 2021 were screened for building the dataset. ASModel_UWF using UWF images was developed. Mean absolute error (MAE) and area under the receiver operating characteristics curve (AUC) were used to evaluate its performance. Saliency maps were generated to make the visual explanation of the model.Results: ASModel_UWF acquired the MAE of the prediction task of 0.83 g/dl (95%CI: 0.81–0.85 g/dl) and the AUC of the screening task of 0.93 (95%CI: 0.92–0.95). Compared with other screening approaches, it achieved the best performance of AUC and sensitivity when the test dataset size was larger than 1000. The model tended to focus on the area around the optic disc, retinal vessels, and some regions located at the peripheral area of the retina, which were undetected by non-UWF imaging.Conclusion: The deep-learning model ASModel_UWF could both predict Hgb concentration and screen anemia in a non-invasive and accurate way with high efficiency.

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“…Intentional review of ocular characteristics identifies at least one abnormally small dimension of the eye structure in 95% of patients with FA ( 151 ). Cross-sectional studies with systematic evaluation have found microcornea in 46–100%, microphthalmia in 69–100%, small palpebral fissures in 75–94%, ptosis in 28–88%, hypotelorism in 25–43%, cataracts in 14–30%, limbal neovascularization in 26–28%, epicanthal folds in 0–9%, strabismus in 7.5%, and posterior embryotoxon in 5% of assessed patients ( 151 , 161 , 162 ). Compared with age- and gender-matched normal values, patients with FA have abnormally diminished: interpupillary distance, inner canthal distance, outer canthal distance, palpebral fissure length, palpebral fissure width, and corneal diameter ( 151 , 161 , 162 ).…”

Section: Dysmorphological and Oncological Phenotype Of Patients With ...mentioning

confidence: 99%

“…This is an interesting finding, since the short palpebral fissure is considered a part of the eye involvement in the PHENOS acronym ( 135 ) and seems to be specific of FA. The limbal neovascularization and cataract were more common in patients who underwent hematopoietic cell transplantation (HCT) ( 161 ). An association between small eyes and a FANCD2 genotype has been found by a single publication ( 37 ).…”

Section: Dysmorphological and Oncological Phenotype Of Patients With ...mentioning

confidence: 99%

“…Optic nerve hypoplasia, characterized by a decreased number of optic nerve axons ( 18 ), can manifest as small disc and cup areas in patients with FA ( 161 , 162 ). The identification of nerve hypoplasia during eye fundus examination should prompt neuroimaging studies, since this ophthalmologic feature may be associated with midline cerebral structural defects, such as the absence of the septum pellucidum , agenesis of the corpus callosum , cerebral hemisphere abnormalities, or pituitary gland anomalies ( 163 ).…”

Section: Dysmorphological and Oncological Phenotype Of Patients With ...mentioning

confidence: 99%

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Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability

et al. 2022

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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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Ocular Manifestations in Patients with Fanconi Anemia: A Single-Center Experience Including 106 Patients

Cited by 6 publications

References 29 publications

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Deep-Learning-Based Hemoglobin Concentration Prediction and Anemia Screening Using Ultra-Wide Field Fundus Images

Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability

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