Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein–coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone–producing cells. We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.)

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the geneGPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Object: Spinal epidural abscess (SEA), once considered a rare occurrence, has showed a rapid increase in incidence over the past 20–30 years. Recent reports have advocated for conservative, nonoperative management of this devastating disorder with appropriate risk stratification. Crucial to a successful management strategy are decisive diagnosis, prompt intervention, and consistent follow-up care. The authors present a review of their institutional experience with operative and nonoperative management of SEA to assess morbidity and mortality and the accuracy of microbiological diagnosis. Methods: A retrospective analysis of patient charts, microbiology reports, operative records, and radiology reports was performed on all cases involving patients admitted with the diagnosis of SEA between July 1998 and May 2009. Results: Seventy-seven cases were reviewed (median patient age 51.4 years, range 17–78 years). Axial pain was the most common presenting symptom (67.5% of cases). Presenting signs included focal weakness (55.8%), radiculopathy (28.6%), and myelopathy (5.2%). Abscesses were localized to the lumbar, thoracic, and cervical spine, respectively, in 39 (50.6%), 20 (26.0%), and 18 (23.4%) of the patients. Peripheral blood cultures were negative in 32 (45.1%) of 71 patients. Surgical site or interventional biopsy cultures were diagnostic in 52 cases (78.8%), with concordant blood culture results in 36 (60.0%). Methicillin-resistant Staphylococcus aureus (MRSA) was the most frequent isolate in 24 cases (31.2%). The mean time from admission to surgery was 5.5 days (range 0–42 days; within 72 hours in 66.7% of cases). Outcome data were available in 72 cases. At discharge, patient condition had improved or resolved in 57 cases (79.2%), improved minimally in 6 (8.3%), and showed no improvement or worsening in 9 (12.5%). Patient age and premorbid weakness were the only factors found to be significantly associated with outcome (p = 0.04 and 0.012, respectively). Conclusions: These results strongly support immediate surgical decompression combined with appropriately tailored antibiotic therapy for the treatment of symptomatic SEA presenting with focal neurological deficit. The nonsuperiority discovered in other patient subsets may be due to allocation biases between surgically treated and nonsurgically treated cohorts. The present data demonstrate the accuracy of peripheral blood culture for the prediction of causative organisms and confirm patient age as a predictor of outcomes.

BACKGROUND:. In this study, we evaluated the use of a part-task simulator with 3-dimensional and haptic feedback as a training tool for percutaneous spi