‘Insights into Fanconi Anemia based on molecular and clinical
characteristics: A multicentre study of 13 Patients’
Abstract
Background: Fanconi anemia (FA) is a rare genomic instability
disorder, characterized by congenital abnormalities, progressive bone
marrow failure and predisposition to cancer. FA is caused by (likely)
pathogenic variants in any of the 23 ( FANCA-FANCY) linked genes.
Procedure: Retrospective analysis of 13 FA patients with a
causative variant was performed to allow insights into FA. Patients (6
boys and 7 girls) aged from 9 to 26 years old, (mean age of 7.3 years),
at diagnosis. Results: Phenotype evaluation demonstrated in
11/13 patients’ congenital anomalies, primarily pigmentary changes and
short stature, in 90% of cases. Haematological abnormalities were
present in 10/11 patients, with thrombocytopenia being the prominent
finding. Genetic analysis for the most common complementation group FA-A
revealed that 12/13 patients belonged to this group and only one patient
was found to be FA-E. Exon deletions, single nucleotide variations, and
duplications were identified. Familial patterns, due to consanguinity,
were evident in one case. Twelve patients underwent hematopoietic stem
cell transplantation (HSCT), with variable pre-HSCT supportive
treatments. Post-HSCT data showed that 9 out of 10 patients for whom
follow up data was available, survived for a median time of 5.4.
Complications like acute graft-versus-host disease were noted.
Conclusions: Our study highlights the importance of
genotype-phenotype correlations towards tailored clinical management
including the optimum time for HSCT in patients with FA.