Whole exome sequencing in Dandy-Walker variant with intellectual disability reveals an activating CIP2A mutation as novel genetic cause.

Dandy-Walker malformation (DWM) has been reported to have heterogeneous causes, including mutations in genes of fibroblast growth factors and in genes in the sonic hedgehog (Shh) signaling pathway. Here, we identified an activating cancerous inhibitor of protein phosphatase 2A (CIP2A) p.D269V mutation, located at the predicted protein-protein interaction groove, as a novel genetic cause of Dandy-Walker variant (DWV). CIP2A has been reported as an oncoprotein promoting tumor survival via inhibition of protein phosphatase 2A (PP2A). However, the impact of human germline CIP2A mutation is unknown. We report a novel heterozygous CIP2A p.D269V mutation via whole exome sequencing in two siblings with DWV and severe intellectual disability who were born to non-consanguineous parents. Only the older brother developed a slow-growing sacral leiomyoma in his teens. The CIP2A p.D269V mutation is associated with increased PP2A, mTOR, and c-Myc protein levels in peripheral blood mononuclear cells (PBMCs). The PP2A phosphatase activity, however, was not suppressed. Deep sequencing revealed that the father carries 16% of somatic CIP2A p.D269V mutation, suggesting potential inheritance from the mosaic sperm populations. Our study is the first to describe a pathogenic CIP2A mutation in humans, which might disrupt neuronal development via enhancing mTOR and c-Myc protein expressions, shedding light in mechanisms of DWV pathogenesis.

Rosai-Dorfman disease mimicking craniopharyngioma: a challenging differential diagnosis. Illustrative case.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytic disorder with less than 5% central nervous system involvement and is often mistaken for meningioma given the similarity in imaging features. The authors present the unique case of a 44-year-old female who presented with ongoing visual impairment. OBSERVATIONS: A purely suprasellar mass was noted on magnetic resonance imaging and was initially diagnosed as craniopharyngioma. Unexpectedly, the pathology report revealed RDD. LESSONS: To date, only six cases of sellar RDD have been reported, and our case is the first reported with a purely suprasellar presentation. No standard treatment has been established for RDD, and next-generation sequencing may be a promising therapeutic option.

Transcatheter arterial embolization in the treatment of maxillofacial trauma induced life-threatening hemorrhages.

BACKGROUND: Life-threatening hemorrhages with hemodynamic instability are uncommon in patients with sustained maxillofacial trauma, but when they occur, require immediate surgical intervention if conservative treatment fails. This study assessed the effects of transcatheter arterial embolization (TAE) in the treatment of maxillofacial trauma-induced life-threatening hemorrhages. METHODS: From January 2004 to January 2007, eight ambulatory patients admitted for maxillofacial injuries with life-threatening hemorrhaging and hemodynamic instability (systolic blood pressure < or = 90 mm Hg) caused primarily by intractable oronasal bleeding who subsequently underwent TAE were included in this study. RESULTS: Maxillofacial trauma was caused by motorcycle traffic injuries (6 cases), motor vehicle injury (1 case), and fall injury (1 case). All patients exhibited documented Le Fort III fractures. The average Glasgow Coma Scale score was 4.7. TAE was successfully performed and hemorrhaging arrested in all patients. Three deaths occurred (38%) from severe traumatic brain injury. The other five patients (62%) survived without development of systemic or neurologic complications post-TAE. CONCLUSIONS: Conservative treatment consisting of packing of the nares, compression, and blood transfusion should always precede TAE as the primary protocol. When conservative treatment fails, as shown either by the need for continued blood product replacement exceeding 1,500 mL and a systolic blood pressure < or = 90 mm Hg, TAE intervention should immediately be considered as an alternative recourse before other surgical interventions.

Duloxetine-Induced Hyponatremia in an Elderly Male Patient with Treatment-Refractory Major Depressive Disorder.

Several classes of antidepressants can induce syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), thereby causing hyponatremia. Initial symptoms of hyponatremia include neuropsychiatric and gastrointestinal manifestations can mimic depression, especially in elderly people with multiple somatic complaints. Here we present a case of a 68-year-old man with treatment-refractory depression and general anxiety disorder who developed duloxetine-induced hyponatremia. His symptoms of hyponatremia including unsteady gait, dizziness, nausea, general malaise, and poor appetite subsided after discontinuing the offending medication. Our case illustrates that drug-induced SIADH and potential drug-drug interactions should be considered in elderly patients who develop hyponatremia following the initiation of antidepressants.

IgG4-related cerebral pseudotumor with perineural spreading along branches of the trigeminal nerves causing compressive optic neuropathy: A case report.

RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) is characterized by tumor-like lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD has been described in a variety of organ systems; however, it rarely involves the central nervous system. PATIENT CONCERNS: A 17-year-old woman visited our clinic with a complaint of blurred vision for the past 5 months. She also reported a painless right submandibular mass that had been present for 1 year. Her best-corrected visual acuity (BCVA) was 2.0 LogMAR, with an almost total visual field defect in the right eye. DIAGNOSES: Magnetic resonance imaging (MRI) revealed lobulated parasellar tumors with perineural spreading along branches of the trigeminal nerves causing right optic nerve compression. A craniotomy with tumor removal and submandibular gland biopsy was performed. Histopathological analysis of the tumor revealed stromal fibrosis with atypical lymphoid infiltrations. Histopathological and immunohistochemical analysis of the submandibular gland confirmed the diagnosis of IgG4-RD. INTERVENTIONS: The patient was administered 500mg/d of pulse methylprednisolone for 3 days, 500mg of intravenous rituximab every 2 weeks (for a total of 2 doses), and 500mg of intravenous pulse cyclophosphamide every month (for a total of 3 doses). OUTCOMES: Two months after the initiation of immunosuppressive therapy, the patient's BCVA returned to 0.1 LogMAR with visual field defect recovery. The follow-up MRI showed the almost complete disappearance of the previously contrast-enhanced lesions. LESSONS: Herein, we report a rare case of IgG4-RD presenting as a parasellar tumor and present a review of the related literature. Based on the case report, we propose that aggressive therapy with glucocorticoid, rituximab, and cyclophosphamide may potentially be useful for treating such cases.