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Journal of Medical Cases

Case Report

Volume 11, Number 9, September 2020, pages 271-274

Congenital Factor VII Deficiency in Association With Bicuspid Aortic Valve and Multicystic Dysplastic Kidney Disease in a Child

Factor VII is a clotting factor that is part of the extrinsic coagulation cascade, which is a vitamin K-dependent factor [1]. Deficiency in this protein results in isolated prolongation of prothrombin time with normal activated partial prothrombin time [2, 3], and correction of this prolongation by 50/50 mixing study with normal plasma can aid the diagnosis by excluding presence of inhibitors [4]. Factor VII deficiency can be either acquired or congenital. The latter is a rare autosomal recessive disorder, reported as 1 in 500,000 [5]. Presentation of this disorder may vary from mild bleeding as in bruising and epistaxis, to severe life-threatening bleeding such as intracranial hemorrhage [3, 4]. In this study, we present a case of factor VII deficiency associated with multicystic dysplastic kidney disease and bicuspid aortic valve disease (BAVD). There has been no direct genetic association between them and such coexistence has not been reported in the literature before.

This is a case of a full-term baby boy, product of an emergency cesarean section due to fetal distress with birth weight of 3,720 g, Apgar score of 7 at 1 min and 9 at 5 min, with no resuscitation being required. The baby was admitted to neonatal intensive care unit (NICU) for 19 days for suspected sepsis, diagnosed at that time with G6PD and congenital factor VII deficiency by picture of bruises all over his body with qualitative G6PD screening test activity positive (deficient), prolonged prothrombin time (PT) of 37.5 s, high international normalized ratio (INR) of 3.9, normal activated prothrombin time (aPTT) of 35.1 s, confirmed by low factor VII level of 0.07; further results are shown in Table 1. Patient was started on regular recombinant activated factor VII. In addition, renal ultrasound was done and showed right multicystic dysplastic kidney disease, later on confirmed by DMSA scan. Patient was discharged from NICU after 19 days. Following this admission, he presented multiple times with bleeding complications in form of rectal bleeding and intracranial hemorrhage (ICH), and subsequently developed post ICH seizure disorder. At 5 months of age, echo was done as follow-up for aortic stenosis that was diagnosed at birth, which showed BAVD with pressure gradient 35 mm Hg, and patent foramen ovale with left to right shunt. There was positive history of consanguinity; mother and father are first-degree cousins. There is also positive family history of congenital factor VII deficiency in patient’s first-degree cousin. Patient has two siblings, one with G6PD deficiency, while the other is healthy.

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Table 1. Laboratory Results of Our Case

BAVD is an inherited condition that results in a malformed, two-leaflet aortic valve, instead of the normal three-leaflet valve.

Cause of this malformation is not completely clear, but recent studies suggest an autosomal dominant component [6]. Another congenital anomaly in our case was multicystic dysplastic kidney disease, which is a congenital maldevelopment, characterized by a non-functioning kidney that contains multiple, varying in size, non-communicating cysts, separated by dysplastic renal parenchyma, and the absence of a normal pelvicaliceal system. It is usually a sporadic disease; however, few familial cases have been reported [7]. Congenital factor VII deficiency is an autosomal recessive disease, which is caused by a genetic mutation in factor VII gene, located on chromosome 13q34 [4, 8]. The unusual combination of the three congenital conditions with their different modes of inheritance makes it even rarer.

Countries with high numbers of consanguineous marriages like Saudi Arabia are at higher risk of congenital factor VII deficiency. During our literature review, there were very few studies on congenital factor VII deficiency in Saudi Arabia. As far as we know, there was only one published case report of a rare association with factor VII deficiency in form of Hirschsprung disease in a new born female with extensive bleeding following an emergency laparotomy due to perforation. Blood work was done and congenital factor VII deficiency was confirmed [9]. A retrospective study conducted in Riyadh, Saudi Arabia, over 8 years, on 168 patients with hereditary bleeding disorder, showed only one patient with factor VII deficiency [10]. Another similar study established in the eastern province on 34 patients showed also one patient with congenital factor VII deficiency [11].

Congenital factor VII deficiency combined with other coagulation factor deficiencies has been stated in the literature. In a critical review of congenital combined deficiency of factor VII, and other factors including V, VIII, IX, X, XII and XIII, no clear genetic association was shown except for the combination of congenital factor VII and X deficiencies. It suggested that, the genes of both factors are very close and located on the long arm of chromosome 13q34; therefore large deletions may result in combined deficiency of both [12, 13]. Another suggested association with 13q deletions was cardiac anomalies, as in our case. A Chinese study proposed that 13q33.1-34 deletions might be related to cardiac development [14]. In the contrary, combined protein C deficiency and congenital factor VII deficiency has been described in a single study [15], the gene for protein C is encoded in chromosome 2, hence the combination of both is random. A number of studies listed in Table 2 [9, 13, 15-29] have shown unique combinations of factor VII deficiency and different associations with no evident explanation.

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Table 2. Rare Associations With Congenital Factor VII Deficiency in the Literature

We present a case of three relatively uncommon disorders, congenital factor VII deficiency, multicystic dysplastic kidney disease and BAVD. It could be a rare association or syndrome, and further cases need to be reported.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

Informed consent was obtained.

Author Contributions

Housam Almadani conceived of the presented idea, developed the theory and performed the computations and supervised the findings of this work. Alsaied, Alzahrani , Albogami, Asiri and Almelibari investigated lab and radiology. All authors discussed the results. Almadani wrote the manuscript and supervised the project. Alsaied and Almelibary contributed to the interpretation of the results. Almadani took the lead in writing the manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript. All authors analyzed the data. Almadani conceived the study. All authors discussed the results and commented on the manuscript.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

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