Objective-Detailed analysis of phenotypic and molecular genetic aspects of Dok-7 myasthenia in 16 patients.Methods-We assessed our patients by clinical and electromyographic studies, by intercostal muscle biopsies for in vitro microelectrode analysis of neuromuscular transmission and quantitative electron microscopy EM of 409 end plates (EPs), and by mutation analysis, and expression studies of the mutants.Results-The clinical spectrum varied from mild static limb-girdle weakness to severe generalized progressive disease. The synaptic contacts were single or multiple, and some, but not all, were small. In vitro microelectrode studies indicated variable decreases of the number of released quanta and of the synaptic response to acetylcholine; acetylcholine receptor (AChR) channel kinetics were normal. EM analysis demonstrated widespread and previously unrecognized destruction and remodeling of the EPs. Each patient carries 2 or more heteroallelic mutations: 11 in genomic DNA, 7 of which are novel; and 6 identifiable only in complementary DNA or cloned complementary DNA, 3 of which are novel. The pathogenicity of the mutations was confirmed by expression studies. Although the functions of Dok-7 include AChR β-subunit phosphorylation and maintaining AChR site density, patient EPs showed normal AChR β-subunit phosphorylation, and the AChR density on the remaining junctional folds appeared normal.Interpretation-First, the clinical features of Dok-7 myasthenia are highly variable. Second, some mutations are complex and identifiable only in cloned complementary DNA. Third, Dok-7 is essential for maintaining not only the size but also the structural integrity of the EP. Fourth, the profound structural alterations at the EPs likely contribute importantly to the reduced safety margin of neuromuscular transmission.Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Between 1995 and 2005, defects in seven end-plate (EP)-associated proteins encoded by 10 different genes have been identified as molecular targets of the CMS. 1 In 2006, Okada and coworkers identified Dok-7 as a muscle-intrinsic activator of MuSK required for synaptogenesis. 2 Dok-7 harbors N-terminal pleckstrin homology (PH) and phosphotyrosineAddress correspondence to Dr Engel, Department of Neurology, Mayo Clinic, Rochester, MN 55905. E-mail: age@mayo.edu. Note Added in Proof Monoallele mutation analysis by the Conversion technology 39 revealed absence of exons 3-6 in one allele in genomic DNA of DOK7 in Patient 9. NIH Public Access Patients and Methods PatientsSixteen patients, 8 men and 8 women, presently 5 to 50 years of age, were investigated. Each patient was initially examined, and four were reexamined 5 to 17 years later after their initial visit (AGE); additional follow-up information came from follow-up letters from referring physicians or patients regarding disease management. All human studies were in accord with guideli...

Klippel-Trenaunay syndrome (KTS) is a rare disorder that consists of a triad of capillary vascular malformation, venous malformations and/or varicose veins, and soft tissue and/or bony hypertrophy. Pain is a real and debilitating problem in these patients. We have observed 9 common causes of pain in KTS: (1) chronic venous insufficiency, (2) cellulitis, (3) superficial thrombophlebitis, (4) deep vein thrombosis, (5) calcification of vascular malformations, (6) growing pains, (7) intraosseous vascular malformation, (8) arthritis, and (9) neuropathic pain. The management of pain in patients with KTS depends on its cause. These patients are best evaluated initially in a center with an experienced multidisciplinary team that includes a primary health care provider, surgeons, and ancillary staff. The ongoing care of a patient with KTS often depends on a local provider who is more readily accessible to the patient but may not have the expertise of a large center to manage the complications of KTS. The purpose of this communication is to review the common causes of pain in these patients to provide local health care providers and patients and their families with appropriate management strategies.

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Level IV, therapeutic study, case series.

Background After bone tumor resection, reconstruction for limb salvage surgery can be challenging because of the resultant large segmental bony defects. Structural allografts have been used to fill these voids; however, this technique is associated with high complication rates. To circumvent the complications associated with this procedure, massive bony allografts have been supplemented with an intramedullary vascularized free fibula. However, few studies have examined the outcomes using this technique in the pediatric and adolescent populations. Questions/purposes The purpose of this study was to examine the revision-free survival using he Capanna technique for limb salvage for pediatric lower limb salvage. We attempted to answer the following questions: (1) What was the overall limb salvage rate along with incidence of reoperation and complications? (2) How did pediatric and adolescent patients functionally perform after this technique? (3) What was the incidence of late complications including infection and fracture? (4) What was the incidence of limb length discrepancy? Methods Eighteen pediatric patients who underwent lower extremity limb salvage with the use of cadaveric allograft and intramedullary free fibular transfer (Capanna technique) were identified. There were nine boys males and nine girls with a mean age of 11 years (range, 5-18 years) and mean followup of 8 years (range, 2-15 years), respectively. All patients had at least 2 years followup. Three patients have not been seen in followup during the past 5-years; however, all had made it to their 5-year clinical followup. The patients' medical records were reviewed for clinical and functional outcomes as well as postoperative complications. Time to union was recorded through an evaluation of radiographs. Mankin functional outcome and Musculoskeletal Tumor Society (MSTS) rating scale were recorded for each patient. Results The overall limb salvage rate was 94%. Fourteen patients underwent an additional surgical procedure. Six patients underwent additional procedure(s) to treat a symptomatic nonunion. Seventeen of the patients had a good or excellent Mankin score with a mean MSTS rating of 93% at last followup. Six of the patients underwent a limb length modification procedure. Conclusions Use of large allografts in conjunction with intramedullary vascularized free fibulas appears to be a reliable method for the reconstruction of large bony tumors of the lower extremity in this population, although we did not directly compare this with allografts alone in our study. The use of locked plates may improve union times. The proportion of patients achieving limb preservation was high and complication rates are acceptable. Level of Evidence Level IV, therapeutic study.

No abstract

The authors’ study evaluates the complications associated with the treatment of clavicle fractures in adolescents. During the study period, 153 clavicle fractures occurred in patients between the ages of 14 and 17 years who were treated at the authors’ center, of which 23 (15.0%) were treated surgically. Compared to the fractures treated nonoperatively, the surgical fractures had greater shortening (mean, 2.0 vs 0.9 cm; P<.001) and were more likely to be comminuted (65.2% vs 23.1%; P<.001). Complications occurred in 21.7% of fractures treated surgically. One delayed union occurred in the nonoperative cohort, but no other complications or patients who required clavicular osteotomy for malunion. Pediatric fellowship-trained orthopedic surgeons treated 78 displaced fractures, resulting in 8 (10.3%) surgeries. Nonpediatric orthopedic specialists treated 46 displaced fractures, 15 (32.6%) of which were treated operatively (P=.0035). FigureA 15-year-old boy sustained a comminuted clavicle fracture from playing football. Preoperative radiograph showing significant clavicle shortening and a vertical fragment.

Level IV, case series.