Factor VII and factor X deficiency in a child with a chromosome 13q duplication and deletion

Combined factor VII (FVII) and factor X (FX) deficiency is a rare bleeding disorder that can be easily misdiagnosed as the laboratory findings can mimic congenital FVII deficiency, vitamin K deficiency or disseminated intravascular coagulation. Patients with combined deficiency of FVII and FX often present with a prolonged PT and a normal APTT. Patients are often asymptomatic or have mild bleeding phenotypes. The disorder can result from large deletions of the long arm of chromosome 13 or coincidental inheritance of separate coagulation factor deficiencies. We report a case of a 10-month-old male with multiple congenital anomalies and partial deletion/duplication of chromosome 13q. Following an abnormal Quad screen (interpreted as an increased risk for Down syndrome), an amniocentesis was performed and was concerning for trisomy 13. Intrauterine ultrasound findings revealed overlapping fingers of bilateral hands (right greater than left), as well as an abnormal profile with sloping forehead and hypoplastic nasal bone. Initial screening FISH results limited to the centromeric region of chromosomes 13, 18, 21, X and Y were normal; however, results from a high-resolution g-banded chromosome analysis were abnormal showing a probable partial duplication of chromosome 13q14-13q33. For this reason, comparative genomic hybridisation (CGH) microarray was performed and results are consistent with a male foetus with clinically significant heterozygous 31.69 Mb duplication of the chromosome 13q21.1-q31.2 region and 9.47 Mb deletion of the chromosome 13q33.2q34 region. The patient’s deletion is known to include the F7 and F10 genes, as well as 49 other genes, and his duplication contains 52 known genes. Parental testing was then pursued to determine if there were any balanced rearrangements that could place them at risk with subsequent pregnancies for similar chromosomal abnormalities. Further work-up found the patient’s mother to have a normal chromosome analysis; however, his father was not available for testing. The patient was born to a 23-year-old G2P1001 mother at 40 and 5/7 weeks via normal spontaneous vaginal delivery with non-reassuring foetal heart tones. Birth weight was 2940 g and APGARs were 8 and 9 at 1 and 5 min respectively. Initial CBC demonstrated a normal WBC and platelet count and haemoglobin of 14.8 g dL 1 with an MCV of 104 fL. The baby and mother both had A+ blood type and the Coombs’ test was negative. An echocardiogram demonstrated an ASD and PDA and was otherwise normal. A head ultrasound showed a small curvilinear echo focus in the left thalamus. Although patients with Trisomy 13 frequently have cleft lip/ palate, polydactyly, microphthalmia, colobomas of the iris and more rarely association of renal anomalies, including hydronephrosis and hydroureter, this patient did not. There was no family history of bleeding or thrombosis and no family history of congenital anomalies. He was circumcised without bleeding on day one of life. At 2 months of age, the patient developed apnoeic spells and was evaluated for apparent life threatening events. At that time, his haemoglobin was 9.8 g dL . The patient had poor weight gain and was diagnosed with failure to thrive. At 3 months of age, he was admitted with emesis and a second time with RSV bronchiolitis. He was found to have a haemoglobin of 8.7 g dL , iron saturation of 12% and was started on oral iron supplementation. At 11 months of age, he was admitted again with fever, emesis and nonbloody diarrhoea. At that time, a laboratory evaluation revealed a creatinine of 6.74 mg dL 1 (which had been 0.25 mg dL 1 at 3 months of age), BUN of 110 mg dL 1 with hyperkalemia >7 mmol L 1 and peaked t-waves. Haemoglobin was 4.7 g dL 1 with an MCV of 77.6 fL and 5% reticulocytes. Haemolyticuraemic syndrome was suspected and nephrology and Correspondence: Michael U. Callaghan, MD, Carmen and Ann Adams Department of Pediatrics, Division of Hematology/ Oncology, Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI, 48201. Tel.: +1 313 745 5515; fax: +1 313 745 5237; e-mail: mcallagh@med.wayne.edu