congenital high-molecular-weight kininogen deficiency

Congenital high-molecular-weight kininogen deficiency is a rare autosomal recessive disorder characterized by an abnormally prolonged partial thromboplastin time without an associated bleeding tendency. It is caused by pathogenic variants in the KNG1 gene, which encodes a protein important in the blood coagulation process. Although the condition is usually identified through laboratory testing rather than clinical symptoms, its discovery often prompts further evaluation. The prevalence of this condition is not well established, underlining its rare occurrence.

The primary clinical finding in individuals with congenital high-molecular-weight kininogen deficiency is a prolonged partial thromboplastin time observed during laboratory testing. Despite this abnormal result, affected individuals generally do not experience bleeding complications or other overt symptoms. Not all individuals present with additional features, and severity can vary considerably between patients.

This condition is caused by pathogenic variants in the KNG1 gene, which is responsible for producing high-molecular-weight kininogen, a key protein in blood coagulation. In an autosomal recessive pattern, both copies of the gene must be affected for the condition to manifest, meaning that each child of carrier parents has a one in four chance of inheriting the disorder. Genetic counseling is recommended for families to understand the inheritance risks and to discuss family planning options.

Currently, management of congenital high-molecular-weight kininogen deficiency focuses on supportive care and symptom management, as there are no specific foundational or targeted treatments available. Treatment plans are tailored to the individual and often involve a multidisciplinary team approach. Patients and their families are encouraged to discuss management options with their healthcare provider and to consider genetic counseling for further guidance.

The outlook for individuals with congenital high-molecular-weight kininogen deficiency is generally favorable, particularly as the condition is not linked to bleeding complications despite its laboratory abnormalities. Outcomes vary based on individual factors and access to specialized care, and many patients maintain a good quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families are advised to connect with genetic counselors and specialists to gain a better understanding of the condition and its management.