Fanconi's anemia, type A presenting as VACTERL association with atresia right external auditory canal

Abstract

Case presentation An infant weighing 2300 g was born at 39 weeks gestation to a 40-year-old gravid 4, para 4 mother. The three other children were reportedly healthy and normal. This pregnancy was complicated by sonographic evidence of intrauterine growth retardation and a twovessel cord. At the time of delivery, the patient was noted to have a hypoplastic pedunculated right thumb and right microtia. Apgar scores were 8 at 1 min and 9 at 5 min. In the neonatal nursery, a nasogastric tube was placed and a skeletal survey (Figures 1 and 2), abdominal sonogram (Figure 3), voiding cystourethrogram ( Figure 4) and a cranial computed tomography were obtained ( Figure 5). The infant underwent a successful repair of the esophageal atresia with distal tracheoesophageal fistula on the fourth day of life. The initial hemoglobin and hematocrit levels were normal, and the mean corpuscular erythrocyte volume was slightly elevated. The platelets and white blood cell counts were normal. A test for hypersensitivity to the effect of the DNA crosslinking agent diepoxybutane (DEB) was ordered. Denouement and discussionThis infant has anomalies of the VACTERL association (esophageal atresia, thumb hypoplasia, vesicoureteral reflux), as well as a first branchial cleft anomaly and atresia of the external auditory canal. The presence of branchial anomalies, hydrocephalus, ophthalmologic anomalies and facial dysmorphism are rare in the VACTERL association, which is a nonhereditary condition with <1% recurrence rate. However, these head and neck abnormalities are more common in genetic conditions associated with esophageal atresia.1 These genetic conditions include Feingold's syndrome (n-MYC gene mutation), CHARGE syndrome (CHD7 mutation), anopthalmia-esophageal-genital syndrome (SOX2 mutation), X-linked VACTERL-H syndrome and Fanconi's anemia (FA). 1,2The DEB test that was conducted in this infant showed increased chromosomal breakage with DEB, consistent with FA. A genetic analysis of the FANC A gene showed a compound heterozygote for

Renal dysplasia characterized by prominent cartilaginous metaplasia lesions in VACTERL association

“…Single-gene disorders resembling the VACTERL association have been reported and include the following: the N-Myc gene in Feingold syndrome, [10,11] the CHD7 gene in CHARGE syndrome, [12] the FANC family of genes in Fanconi anemia, [13,14] the SALL1 gene in Townes–Brocks syndrome, [15] and the GLI3 gene in Pallister–Hall syndrome. [16] …”

Fanconi anaemia with bilateral diffuse pulmonary arterio venous fistulae: a case report

“…One is the VACTERL abnormality [5]. Complementation Group A Fanconi anaemia patient presenting with VACTERL association and atresia of the right ear has been reported [6]. FA with hydrocephalus and VACTERL have also been reported recently [7].…”

Facial palsy: a rare manifestation in Fanconi anaemia

“…3 It is associated with progressive bone marrow failure, congenital anomalies, growth retardation, hyperpigmentation of the skin, cafe au lait spots and a predisposition to malignancies, especially acute myelocytic leukemia and squamous cell carcinoma. 4 About 75% of patients with Fanconi anemia have birth defects, such as altered skin pigmentation and/or café au lait spots (>50%), short stature (50%), thumb or thumb and radial anomalies (40%), abnormal male gonads (30%), microcephaly (25%), eye anomalies (20%), structural renal defects (20%), low birth weight (10%), developmental delay (10%), abnormal ears or hearing (10%). 5 In the present case, patient presented with short stature, hypo/hyper pigmented patches over skin, mild microcephaly, microphthalmia, pallor, bilateral absent thumbs and presence of supernumery thumb.…”

“…4 Fanconi anemia can be accurately diagnosed using diepoxybutane (DEB) induced chromosome breakage which is highly specific. The cells of patients with FA are characterized by chromosomal hypersensitivity to cross linking agents and the resulting increase in chromosome breakage provides the basis for a diagnostic test.…”

“…8 In general bone marrow transplantation should be performed at a young patient age, before the use of androgens and with normal platelet levels at the initiation of the transplant, has been associated with a good survival. 4 Androgens, especially oxymetholone to increase bone marrow cellularity. The latter drug is associated with increased risk of acne, hyperactivity, premature epiphyseal closure and hepatic tumors.…”