The Utility of Factor VIII Infusion in a Rare Case of SHAM Syndrome (P4.343)

Background: Hemophilia A and Moyamoya have been associated with a rare genetic syndrome known as SHAM syndrome characterized by genetic deletions in Xq28 involving both F8 and BRCC3 genes. With a combined risk of both ischemic and hemorrhagic stroke, optimal treatment for this rare entity has not been adequately described. Case report: A 21-year-old Dominican man with severe hemophilia A (requiring scheduled factor VIII treatments), essential hypertension, skeletal dysplasia, and learning disability presented after losing consciousness. Upon awakening, he complained of severe headaches, had a systolic blood pressure of 270 mmHg and quickly progressed to coma. CT head revealed a right subdural hematoma with 9mm of midline shift. Desmopressin and factor VIII were administered followed by an urgent hemicraniectomy. Follow-up MRI/A brain imaging unexpectedly revealed bilateral intracranial carotid artery stenosis and extensive collateralization. Digital subtraction angiography confirmed the diagnosis of Moyamoya disease. His postoperative course was complicated by status epilepticus in addition to recurrent right frontal 100cc intracerebral hemorrhage requiring clot evacuation and lobectomy. Given his recurrent hemorrhage, a factor VIII infusion was started at 3.5IU/kg/hr for 5 days with transition back to 3 times a day dosing with no further hemorrhage or ischemia on follow-up stability imaging. Genetic testing was sent for SHAM syndrome. His clinical exam improved and he was eventually extubated and discharged to rehab with moderate left sided weakness. Conclusions: Genetic testing confirmed the presence of SHAM syndrome with an 83 kb deletion involving both F8 and BRCC3 genes responsible for severe hemophilia and Moyamoya disease respectively. This case illustrates the first phenotypically and genetically confirmed adult case of SHAM syndrome with intracerebral hemorrhage and highlights the utility/safety of factor VIII infusion in this case. Disclosure: Dr. Roh has nothing to disclose. Dr. Roth has nothing to disclose. Dr. Al-Mufti has nothing to disclose. Dr. Chung has nothing to disclose. Dr. Connolly has nothing to disclose. Dr. Eisenberger has nothing to disclose. Dr. Park has nothing to disclose. Dr. Claassen has received personal compensation for activities with the JSMF Foundation, Actelion, and SAGE Pharmaceutical. Dr. Agarwal has nothing to disclose.