A Perspective of Fanconi Anemia and Its Association with Skeletal Anomalies in Northwestern Iran (original) (raw)
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Fanconi anemia: in all its glory
International Journal of Research in Medical Sciences, 2015
INTRODUCTION Fanconi Anemia (FA) is a rare genetic disorder characterized by progressive bone marrow failure, 1 variable congenital anomalies and a high predisposition to acute leukemia and other malignancies. 2 FA shows severe genetic heterogenicity, although the proteins encoded by FA-related genes are considered to work together in a common pathway that regulates cellular resistance to DNA cross-linking agents. At least 15 genes have been identified that are responsible for FA complementation groups: FANCA, FANCB, FANCC, BRCA2 (FANCD1), FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI, FANCM, BRIP1 (FANCJ or BACH1), FANCL, RAD51C (FANCO), and SLX4 (FANCP), PALB2 (FANCN). 3-5 Abnormalities of FA genes are inherited as autosomal recessive, except for FANCB mutations, which are inherited in an X-linked manner. Molecular diagnosis of FA is very complicated because at least 15 genes are associated with its development & the mutation spectra of most FA-associated genes are very diverse. Some of these genes frequently contain large deletions or duplications. 6 CASE REPORT An 8-year-old male presented with complaints of not gaining weight and repeated episodes of vomiting since one year. He was a full term, normally delivered child. Physical examination of the patient revealed microcephaly, short stature, triangular facies, epicanthal folds, wide nasal bridge, bat ears (Figure 1), hyperpigmented tongue (Figure 2), microglossia, micrognathia, Sprengel's deformity (Figure 3), absent right thumb (Figure 4), rudimentary left thumb (Figure 5), genu valgum and bilateral retractile testis. He had multiple café-au-lait spots on left shoulder (Figure 6), left arm and both thighs. His initial complete blood cell count results showed white blood cell: 3.5×10 9 /L; hemoglobin: 5.5 g/dL; platelets: 29 × 10 9 /L. Repeat hemogram indicated persistent thrombocytopenia. Peripheral smear showed macrocytic, normochromic erythrocytes. Bone ABSTRACT Fanconi Anemia (FA) is a rare autosomal recessive disorder affecting multiple body systems. The diagnosis is based on morphological abnormalities, hematological abnormalities (pancytopenia, macrocytic anemia & progressive bone marrow failure) and genetic testing. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large duplications, deletions or sequence variations are frequently observed in some of these genes. We report a patient with cytogenetically confirmed Fanconi anemia. Although morphological abnormalities were present from birth, diagnosis was suspected and made at 8 years of age when he presented to us. We report this case to create awareness among clinicians to use modern modalities of diagnosis for such cases in addition to the clinical assessment. This would further help these children reach their adulthood with good quality of life.
Medical Laboratory Journal, 2023
Background and objectives: Fanconi anemia (FA) is an autosomal recessive disorder that usually manifest in forms of pancytopenia, hyperpigmentation, and skeletal complications. Mutation in the DNA repair regulatory genes is associated with the development of FA. Examination of chromosomal breakages when chromosomes are exposed to cross-linking agents is a common method of FA diagnosis. This study aimed to evaluate the prevalence and characteristics of patients with FA in Mashhad, northeast of Iran. Methods: In this study, we evaluated 312 suspected FA patients who had been referred to the laboratory of Ghaem Hospital during 2014-2020. The mitomycin C method was used to identify FA-positive subjects. Results: After the examinations, 84 patients (26.9%) were cytogenetically positive for FA. Of 84 patients, 48 (57.1%) were male and 36 (42.9%) were female. Thumb abnormality was the most common congenital anomaly (43.2%). Conclusion: Based on the findings, males are more susceptible to FA, and thumb abnormality is the most common congenital anomaly associated with FA. Combination of clinical manifestations and genetic susceptibility in patients may contribute to a more accurate diagnosis.
The Journal of Hand Surgery, 2011
Purpose Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive.
Fanconi Anaemia – A Rare Case Report
Bangladesh Medical Research Council Bulletin
Fanconi anaemia is a rare and most common form of inherited aplastic anaemia. It is mostly autosmal (except one x link) recessive disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to both haematological malignancy and solid tumours. Congenital malformation varies from patient to patient and may affect the skeletal system as well as organ systems. Highly variable phenotypic presentation with clinical menifestations makes difficult for diagnosis in some cases. Chromosomal breakage study induce by Mitomycin-C (MMC)/Diepoxybutane(DEB) provide a unique cellular marker for the diagnosis.The incidence of FA is approximately 1 to 5 per million. In Bangladesh, so far no study or even any case was reported. In this case report, a two years nine months old male child presented with generalized weakness , recurrent episodes of fever and physical deformities. It was found him short stature, microcephaly, trianguler face,generalized hyperpigmentation with café au lait spots,absent both thumbs with flexor deformity of both wrists. Peripheral smear found bicytopenia, bone marrow aspiration and biopsy showed hypoplastic marrow mildly elevated LDH, X-ray and USG showed bone and organ agenesis and chromosomal breakage study is also positive.
Fanconi Anemia: From The Perspective of Hand Surgery
FANCONI ANEMIA AND OTHER INHERITED BONE MARROW FAILURE SYNDROMES, 2021
Fanconi anemia is a heterogenous clinical condition requiring a multidisciplinary approach whereas these patients are frequently born with upper limb anomalies and are often referred to a hand surgeon long before the diagnosis of the underlying disease. Hand specialists have the responsibility to refer these patients with high risk to pediatrics/hematology specialists for Fanconi testing. Treatment of congenital diff erences of the upper extremity is a signifi cant challenge. From the perspective of hand surgery, the goal is to achieve a functioning limb that should be satisfactorily treated for the child’s physical, social and emotional development. In means of postoperative results, specialized therapy and rehabilitation is as important as proper evaluation and skillful surgical approach.
Fanconi Anemia Concurrent with an Unusual Thumb Polydactyly: A Case Report
The archives of bone and joint surgery, 2016
This case report presents a case of Fanconi's Anemia with an unusual thumb polydactyly in a 2-year-old boy. The extra thumb had no nail, nail bed and distal phalanx. The extra thumb had no active motion. The duplication of the thumb occurred at the carpometacarpal joint but its morphology did not match with any classification described for thumb polydactyly. Although his thumb polydactyly was apparent at birth, Fanconi's anemia was not suspected until during a routine pre-operative laboratory test (CBC) for the elective surgery of his thumb. An early diagnosis of FA is important and the hand surgeons may be the first to have the opportunity to suspect and diagnose the underlying life threatening disorder. This case report presented an opportunity to diagnosis a fatal disorder by a routine pre operative laboratory test. To the best of my knowledge, the phenotype of the thumb polydactyly of the current case has not yet reported.
Fanconi anemia and its diagnosis
Mutation research, 2009
Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to both hematologic malignancies and solid tumors. Congenital anomalies vary from patient to patient and may affect skeletal morphogenesis as well as any of the major organ systems. Although this highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, laboratory study of chromosomal breakage induced by diepoxybutane (DEB) or other crosslinking agents provides a unique cellular marker for the diagnosis of the disorder either prenatally or postnatally. Diagnosis based on abnormal response to DNA crosslinking agents can be used to identify the pre-anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. This overview will present our current knowledge regar...
A Review of Fanconi Anemia for the Practicing Pediatrician
Pediatric annals, 2015
Early recognition of a patient who might have Fancomi anemia by the general pediatrician and referral to a tertiary care center with a dedicated cancer risk program is critical for early diagnosis. Genetic testing and close multidisciplinary surveillance is required for patients with this syndrome and their families because of its multisystem involvement and propensity for early-onset bone marrow failure and leukemic transformation. This article reviews the clinical symptoms and signs, radiologic findings, and screening guidelines of FA for the general pediatrician. [Pediatr Ann. 2015;44(10):444-445,448,450,452.].
From Surgery to Hematology: Fanconi Anemia about a Case of a Senegalese Child
Open Journal of Pediatrics, 2020
Fanconi anaemia (FA) is a rare genetic abnormality. Most of FA reported from the sub-Saharan population came from southern Africa, with many patients linked to a mutation in the FANC G gene. Classic triads of this disorder are: a varied malformation, bone marrow failure, and short stature. This disorder is also associated with predisposition to malignancies. These multiple manifestations, sometimes not uniform, often cause diagnostic delay. We here report a 13-year-old Senegalese boy with FA. He was followed up for polydactyly-repair surgery. Importantly, pre-operative blood check-up revealed severe anaemia, which prompted us to perform bone marrow aspiration: examination revealed dysmyelopoiesis. Being triggered by this, systematic examinations were performed, which revealed other signs indicative of FA; i.e., radial spine abnormalities, triangular face, etc. The diagnosis of FA was strongly suggested, which prompted genetic examination. The chromosomal breakage test detected cellu...
An update on Fanconi anemia: Clinical, cytogenetic and molecular approaches (Review)
Biomedical Reports, 2021
Fanconi anemia is a genetic syndrome clinically characterized by congenital malformations that affect several human systems, leads to progressive bone marrow failure and predisposes an individual to cancer, particularly in the urogenital area as well as the head and neck. It is commonly caused by the biallelic compromise of one of 22 genes involved in the FA/BRCA repair pathway in most cases. The diagnosis is based on clinical suspicion and confirmation using genetic analysis, where the chromosomal breakage test is considered the gold standard. Other diagnostic methods used include western blotting, multiplex ligation-dependent probe amplification and next-generation sequencing. This genetic condition has variable expressiveness, which makes early diagnosis difficult in certain cases. Although early diagnosis does not currently allow for improved cure rates for this condition, it does enable healthcare professionals to perform a specific systematic follow-up and, if indicated, a bone marrow transplantation that improves the mobility and mortality of affected individuals. The present review article is a theoretical revision of the pathophysiology, clinical manifestations and diagnosis methods intended for different specialists and general practitioners to improve the diagnosis of this condition.