This type of myopathy may represent a previously unrecognized manifestation of CS. However, some patients carrying HRAS mutations may exhibit prominent congenital muscular dysfunction, although features of CS may be less obvious, suggesting that germline HRAS mutations may underlie some cases of otherwise unclassified neonatal neuromuscular disorders.

We performed histologic and immunohistochemical analysis of cerebellar sections from a preterm infant (32 weeks 5 days) dead on the 4th day of life with the diagnosis of kernicterus and compared the results with 1 age-matched nonicteric patient. Poorer Luxol fast blue-periodic acid Schiff and Bodian-Luxol fast blue stainings as well as neurofilament expression were observed in the kernicterus case, indicating loss of axon neurites and myelin fibers. Elevated claudin-5 and cluster of differentiation 34 expression associated with increased blood vessel density suggests bilirubin-induced angiogenic sprouting. Upregulation of vascular endothelial growth factor and its receptor 2 was observed in nucleus dentatus and Purkinje neurons. Although upregulation of multidrug resistance-associated protein 1 was increased in cerebellar neurons, it was not able to prevent bilirubin-induced neurotoxicity. These data add new insights into the pathophysiology of kernicterus, revealing vascular endothelial growth factor and its receptor 2, as well as angiogenic sprouting, as new players in neurologic damage by unconjugated bilirubin.

Introduction:Ryanodine receptor gene (RYR1) mutations have been associated with central core disease (CCD), multiminicore/minicore/multicore disease (MmD), and susceptibility to malignant hyperthermia (MH).Methods:Patients with muscle symptoms in adulthood, who had features compatible with CCD/MmD, underwent clinical, histological, and genetic (RYR1 and SEPN1 genes) evaluations. Published cases of CCD and MmD with adult onset were also reviewed.Results:Eight patients fulfilled the criteria for further analysis. Five RYR1 mutations, 4 of them unreported, were detected in 3 patients. Compound heterozygosity was proven in 1 case.Conclusions:To our knowledge, this is the only report of adult onset associated with recessive RYR1 mutations and central core/multiminicores on muscle biopsy. Although adult patients with CCD, MmD, and minimally symptomatic MH with abnormal muscle biopsy findings usually have a mild clinical course, differential diagnosis and carrier screening is crucial for prevention of potentially life‐threatening reactions to general anesthesia. Muscle Nerve 44: 102–108, 2011

✓Papillary glioneuronal tumors (PGNTs) are rare lesions of the central nervous system, and no information exists on the genetic alterations in these neoplasms. The authors report on such a case in a child. Genetic studies revealed that the tumor was characterized by gains and structural alterations involving only chromosome 7 with breakpoints at 7p22. By using comparative genomic hybridization, the authors observed a high-level amplification region at 7p14~q12. Fluorescence in situ hybridization with a probe for EGFR revealed that this gene was not amplified. Similar to other patients with PGNTs, the patient in the present case fared well. From a genetic point of view the data in the present case are in accordance with previous findings of EGFR amplifications as uncommon in low-grade gliomas and gangliogliomas. Recurrent rearrangements of chromosome 7 have been noted in other mixed glioneuronal tumors. The data in this case suggest that genes located at chromosome 7 can also be involved in the pathogenesis of PGNT. In clinical terms it will be especially important to corroborate, through the analysis of further cases, the involvement of the chromosome 7p22 locus, a region where glial and neuronal linked genes (RAC1 and NXPH1) are known to be located.

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