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High molecular weight kininogen deficiency

MedGen UID:
75780
Concept ID:
C0272340
Disease or Syndrome
Synonyms: Congenital high-molecular-weight kininogen deficiency; FITZGERALD TRAIT; Flaujeac factor deficiency; Reduced kininogen activity
SNOMED CT: Fitzgerald-Flaujeac-Williams-Reid trait (27312002); High molecular weight kininogen deficiency (27312002); Fitzgerald factor deficiency (27312002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): KNG1 (3q27.3)
 
HPO: HP:0005527
Monarch Initiative: MONDO:0009234
OMIM®: 228960
Orphanet: ORPHA483

Definition

High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985). [from OMIM]

Clinical features

From HPO
Prolonged partial thromboplastin time
MedGen UID:
66815
Concept ID:
C0240671
Finding
Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.
High molecular weight kininogen deficiency
MedGen UID:
75780
Concept ID:
C0272340
Disease or Syndrome
High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHigh molecular weight kininogen deficiency
Follow this link to review classifications for High molecular weight kininogen deficiency in Orphanet.

Conditions with this feature

High molecular weight kininogen deficiency
MedGen UID:
75780
Concept ID:
C0272340
Disease or Syndrome
High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985).

Recent clinical studies

Etiology

Schmaier AH
Curr Opin Hematol 2016 Sep;23(5):445-52. doi: 10.1097/MOH.0000000000000271. PMID: 27380557Free PMC Article

Diagnosis

Yang J, Fan L, Qiao Y, Zhao Y, Zhu T
J Thromb Thrombolysis 2020 Nov;50(4):989-994. doi: 10.1007/s11239-020-02088-6. PMID: 32185598
Hathaway WE, Assmus SL, Montgomery RR, Dubansky AS
Am J Clin Pathol 1979 Jan;71(1):22-5. doi: 10.1093/ajcp/71.1.22. PMID: 420168
Saito H, Goldsmith GH Jr
Blood 1977 Sep;50(3):377-85. PMID: 884316

Therapy

Saito H, Goldsmith GH Jr
Blood 1977 Sep;50(3):377-85. PMID: 884316

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