Genetics, diagnosis and clinical features of congenital hypodysfibrinogenemia: a systematic literature review and report of a novel mutation

Genetics, diagnosis and clinical features of congenital hypodysfibrinogenemia: a systematic literature review and report of a novel mutation
Congenital fibrinogen disorders are usually caused by deficiency or functional defects in the molecule. Hypodysfibrinogenemia has features of both quantitative and qualitative defects, and is often misdiagnosed as simply hypofibrinogenemia. Various genetic aberrations were reported in previous publications, including heterozygosity and compound heterozygosity for nonsense and missense mutations.
The authors describe a case suggesting hypodysfibrinogenemia and leading to genetic analysis of the three fibrinogen genes (FGA, FGB, FGG). Subsequently, the authors performed a systematic review of the literature for studies of hypodysfibrinogenemia and compiled these results to identify the breadth of genetic aberrations associated with this entity.
The literature review identified 32 single mutations in 51 patients with hypodysfibrinogenemia, which were mainly missense and nonsense mutations. Compound heterozygosity for mutations known to cause both hypo- and dys-fibrinogenemia was also noted. Clinically, these patients had a wide variety of clinical symptoms, including both bleeding (45%) and thrombosis (44%).
This is a systematic review of case reports and small series. While the literature search was thorough, this is a major limitation, and subject to both reporting and publication bias.
Hypodysfibrinogenemia is a rare condition caused by a wide variety of molecular abnormalities and leading to a wide range of clinical presentations. Both antigenic and functional measurements of fibrinogen are necessary to ensure that it is not misdiagnosed as hypofibrinogenemia.