Patterns and frequency of renal abnormalities in Fanconi anaemia: implications for long-term management

Abstract

BackgroundFanconi anaemia (FA) is an inherited disease with bone marrow failure, variable congenital and developmental abnormalities, and cancer predisposition. With improved survival, non-haematological manifestations of FA become increasingly important for long-term management. While renal abnormalities are recognized, detailed data on patterns and frequency and implications for long-term management are sparse.MethodsWe reviewed clinical course and imaging findings of FA patients with respect to renal complications in our centre over a 25-year period to formulate some practical suggestions for guidelines for management of renal problems associated with FA.ResultsThirty patients including four sibling sets were reviewed. On imaging, 14 had evidence of anatomical abnormalities of the kidneys. Two cases with severe phenotype, including renal abnormalities, had chronic kidney disease (CKD) at diagnosis. Haematopoietic stem cell transplantation was complicated by significant acute kidney injury (AKI) in three cases. In three patients, there was CKD at long-term follow-up. All patients had normal blood pressure.ConclusionsEvaluation of renal anatomy with ultrasound imaging is important at diagnostic workup of FA. While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD increases with age, in particular after haematopoietic stem cell transplantation. Monitoring of renal function is essential for management of FA. Based on these long-term clinical observations, we formulate some practical guidelines for assessment and management of renal abnormalities in FA.Electronic supplementary materialThe online version of this article (10.1007/s00467-018-3952-0) contains supplementary material, which is available to authorized users.

Urothelial carcinoma within the prostatic utricle of an adult with hypospadias and Fanconi anemia

“…Although physical abnormalities among patients with Fanconi anemia are well described, this is the first report of a patient with Fanconi anemia and a prostatic utricle. In the literature, Fanconi anemia has been associated with absent or malformed kidneys and other defects of the urinary tract; however, presence of a prostatic utricle, let alone the additional presence of urothelial carcinoma within the prostatic utricle, has not been described 1 . Common presenting symptoms of patients with an enlarged prostatic utricle include irritative lower urinary tract symptoms, as in this patient, and hematospermia 4 .…”

“…Fanconi anemia is an autosomal recessive disorder involving DNA repair, with associated with defects in spermatogenesis, renal abnormalities, and predisposition for hematologic malignancies 1 . To date, there is no known association between Fanconi anemia and prostatic utricles, a Mullerian duct structure in males homologous to the female vagina, cervix, and uterus.…”

Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations

“…The radial ray defects in combination with IUGR, microcephaly and renal defects suggest an overlapping phenotype between LIG4 syndrome and Fanconi anaemia (FA, MIM 227650 ), a clinically and genetically heterogeneous autosomal recessive disorder which like LIG4 syndrome impacts on the DNA damage repair pathway, and can present with multiple congenital anomalies, including lethal antenatal presentation ( Table 1 ). Approximately half of all patients with FA have renal involvement, including dysplastic, pelvic, malrotated kidneys, crossed fused ectopia, horseshoe, and multicystic kidneys ( Sathyanarayana et al, 2018 ).…”

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

“…The relevance of stochastic factors in developmental phenotypes is also illustrated by renal malformations. The patterns of abnormalities found in these paired organs, point to disruption of migration patterns of embryonal organs to their final position occurring at an early developmental stage, suggesting that the FA pathway may have a role in this [89]. A literature review estimates a frequency of kidney malformations in nearly 30% of patients [8], but this seems to be an A more flagrant misestimation of occurrence is found for skin pigmentation changes, which have been described in almost 40% of published cases of patients with FA [8].…”