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

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.

Postoperative Adverse Outcomes in Intellectually Disabled Surgical Patients: A Nationwide Population-Based Study

“…Several coexisting clotting defects have been reported in patients with ID, including factor V [28], factor VII (alone [29] or in combination with factor X [30]), and factor XI (alone [31] or in combination with factor XII [32]). Complicated bleeding diathesis (decreased factor XI, XII, von Willebrand's factor and platelet dysfunction) in some ID patients might be further exacerbated by physiological alterations in specific conditions (such as pregnancy) and result in postoperative bleeding [33].…”

Rare Bleeding Disorders in Children: Identification and Primary Care Management

“…36,37 FX deficiency has been associated with various noncoagulation-related abnormalities, including thrombocytopenia-absent radius syndrome, mitral valve prolapse, hypertrophic cardiomyopathy, and hypercholesterolemia. 52 FV deficiency is sometimes confused with FV Leiden. FV deficiency is an inherited disorder characterized by low levels of FV due to mutations in the FV gene, which preclude the synthesis of this procoagulant protein.…”

Severe FX deficiency caused by a previously unidentified 4‐bp deletion compound heterozygous with a large deletion involving FVII and FX genes

“…Gross genomic DNA re‐arrangements/deletions can be missed by conventional PCR and sequence analysis and remain unidentified. FX deficiency has been rarely associated with other factor deficiencies, particularly FVII [2]. Combined FX and FVII deficiency may result from the close proximity of FVII and FX genes at chromosome 13q34 as is the case here (Fig.…”

“…We could show that the child inherited a large deletion involving both the FVII gene and at least part of the FX gene, from the mother. Combined FX and FVII deficiency, as a result of gross chromosomal aberrations, has been associated with mental retardation, cleft palate and ventricular septal defects which were not present here [2]. For this reason, we did not further characterize the breakpoints of the 13q34 deletion.…”