Congenital FX deficiency combined with other clotting defects or with other abnormalities: a critical evaluation of the literature

Haemophilia. 2008 Mar;14(2):323-8. doi: 10.1111/j.1365-2516.2007.01612.x. Epub 2007 Dec 10.

Abstract

The presence of more than one congenital clotting defect in a given patient is a rare event but not an exceptional one. Combined defects of factor X (FX) are very rare because congenital isolated FX deficiency is by itself very rare. A perusal of personal files and of the literature has yielded 12 families with FX deficiency in which an association with another clotting factor deficiency was found. The associated defects were factor VII (FVII) or factor VIII (FVIII) or factor XII (FXII) deficiency. By far the most frequently associated was with FVII. Two forms of this association were found. In the first form there is casual association of both FVII and FX deficiency in the proband with independent recessive segregation of the two defects in other family members. The second form is because of abnormalities in chromosome 13 (deletions, translocations and so on) involving both FX and FVII genes. These genes are known to be very close and located on the long arm of chromosome 13 at about 13q34. In this form the hereditary pattern is autosomal dominant. Isolated FX deficiency and, more frequently, combined FX + FVII deficiency appear also associated with coagulation-unrelated abnormalities (carotid body tumours, mitral valve prolapse, atrial septal defect, ventricular septal defect, thrombocytopenia absent radius (TAR) syndrome, mental retardation, microcephaly and cleft palate). Diagnosis of a combined clotting defect could be difficult on the basis of global tests. For example, both isolated FX deficiency and combined FX + FVII deficiency yield a prolongation of basal PTT and PT. Only specific assays could allow one to reach the correct diagnosis. In cases of casual association with other defects, it is also important to study family members, as the two defects should segregate independently.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Blood Coagulation Disorders, Inherited / complications*
  • Child
  • Factor VII / genetics
  • Factor VII Deficiency / complications
  • Factor VIII / genetics
  • Factor X / genetics
  • Factor X Deficiency / complications*
  • Factor X Deficiency / genetics
  • Factor XII Deficiency / complications
  • Female
  • Genes, Dominant
  • Hemophilia A / complications
  • Humans
  • Male
  • Middle Aged

Substances

  • Factor VII
  • Factor VIII
  • Factor X