PB0204 - Correlation Between the Clinical Phenotype and Genotype Profiles in Children with Congenital Factor VII Deficiency

Background: Congenital Factor VII (FVII) deficiency is a rare coagulation disorder with variable clinical phenotypes due to homozygous, compound-heterozygous, or single-heterozygous mutations within the FVII gene. FVII activity levels do not correlate with severity. The role of genetic analysis in predicting clinical phenotype remains unknown.

Aims: To investigate the correlation between clinical phenotype and genotype profiles among children with congenital FVII deficiency at a single hemophilia treatment center.

Methods: After obtaining IRB approval, a retrospective chart-review between 2012-2022 was performed. Patients < 22 years-of-age with congenital FVII deficiency were included. Clinical characteristics and genotype analyses were collected when available.

Results: Eighty-one patients were identified. Table 1 shows clinical characteristics. The mean FVII activity level was 45.6% (range 5%-91%). Epistaxis (48.1%), heavy menstrual bleeding (42.0%), easy bruising (38.3%), and iron-deficiency anemia (IDA) (38.3%) were commonly reported. IDA was more prevalent among post-menarchal females (73.5%; p< 0.001), with 17.6% requiring a blood transfusion.

Seventy-four patients underwent genetic analysis. Fifty-nine (79.7%) had an identifiable mutation in the FVII gene, most commonly within the p.R353Q polymorphism (84.7%). Interestingly, the identification of a characteristic FVII mutation was diagnostic in 18 (24.3%) genetically tested patients who had suggestive phenotypes but normal FVII activity levels.

Inheritance patterns varied including single-heterozygous (61.0%), compound-heterozygous (20.3%), and homozygous (18.6%) mutations. Patients with homozygous or compound-heterozygous mutations had significantly lower mean FVII activity levels than those with single-heterozygous mutations (36.1% and 40.2% vs. 56.7%; p< 0.05). However, no significant correlation between inheritance pattern and clinical severity was identified (Table 2).

Conclusion(s): Congenital FVII deficiency is associated with a spectrum of phenotypes and genotypes. Identifying a characteristic FVII mutation may be essential to establishing a diagnosis, especially among patients with bleeding tendencies and normal FVII activity levels. Inheritance pattern was not associated with clinical severity in our cohort but larger studies are needed.