Fanconi Anemia (FA) is a rare inherited condition that may present with bone marrow failure (BMF), constitutional anomalies and high risk of developing cancer. A significant number of FA patients are seen in regions with higher rate of consanguinity and large family sizes, as in the Middle East. Large numbers of FA patients are referred to and treated in KFSHRC. We Studied the clinical characteristics and outcomes of adolescent and young adult (AYA) patients with a diagnosis of FA treated at our institution.


A prospective study of Saudi patients with FA that presented to KFSHRC was obtained from an institutionally approved BMF database and hematopoietic stem cell transplant (HSCT) database. Cases were enrolled only if they were older than 14 years of age at the time of diagnosis or under the care of adult hematology with a clinical diagnosis of FA based on the presence of BMF and abnormal CB, or clinical phenotype with the presence of homozygous FA related genes. Family pedigrees were constructed based on history.

In addition, patients presenting with BMF were enrolled onto an institutionally approved study investigating proteomic biomarkers and genomics of BMF syndromes. Consented peripheral blood samples and/or extracted DNA were subject to either panel based next generation sequencing (NGS) testing as part of the Saudi Genome Project or subjected to whole exome sequencing (WES) by external lab.


Patients and clinical features: a total of 97 patients (43 M, 54 F) in 60 families were identified and characterized. The median age of diagnosis was 14 years. The parental consanguinity among patients was 51%.The most frequent anomaly was short stature (45 patients, 65%), skin changes (11, 15%), urogenital abnormalities (21, 30%), dysmorphism/craniofacial abnormalities (25, 36%);A significant minority of patients (29%) had no other physical anomaly and presented with bone marrow failure or hematological malignancy.

Diagnostic Tests: 68 patients (70%) had a positive CB analysis with diepoxybutane (DEB) or mitomycin-C (MMC) testing; in 5 patients (5%) DEB testing was borderline and 1 (1%) had a normal CBA but had a diagnostic phenotype/- family history and presence of a homozygous mutation in a known FA related gene. 33 patients had cytogenetic abnormalities and abnormalities involving chromosome 1 were the most frequent (50%).

Mutation Analysis: Mutational analysis was available for 20 (21%) cases;a farther 15 cases had a presumed mutation.FANCA (23 patients/8 families); BRIP1 (2/2); FANCP (1/1); FANCD2 (5/2) FANCI(2/1);FANCG(2/2).

Malignancies: 30 patients (31%) developed a malignancy either before or after diagnosis of FA: solid tumors in 8 (27%), AML and/or MDS in 17 (57%); 5 (16%) of these patients had both solid tumors and AML/MDS.The median age of cancer diagnosis was 27 years (range:7-48).Among patients developed solid tumor (46%) had head and neck SCC,(15%) had HCC,(8%) had lung cancer,(8%) had colon cancer , (8%) had cervical cancer and(8%) had esophageal cancer.

Treatment outcomes: 74 out of 97 patients (76%) received HSCT. Actuarial survival of HSCT (n=56) and non-HSCT (n=11) patients was 75% and 58%, respectively. Treatment details were not available on 3 (3%). (11 %) Received FLU/CY /ATG.Low dose TBI was incorporated in 67%.

Survival: Overall survival at 5 years was 37.8 %. The median overall survival Among non-transplanted patients was 28.8 months (95%CI 26.3-31.4) and it was 41.6 months (95% CI 28.1-55.03) among transplanted patients. (27%) died of solid tumor post-transplant, (22%) developed SCC and( 5%) developed HCC.


We report long term outcomes of a large cohort of AYA patients with FA in Saudi Arabia.FANCA is the most frequent gene affected.

FA patients have a significant risk of malignancies that reduces survival. Early detection and screening of malignancies is crucial. Further progress is required in improving outcomes in transplanted patients with reduced toxicity and less genotoxic therapies , including gene therapy.

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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