Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Musculoskeletal deficits remain significant impediments to the function and independence of children and adolescents following successful treatment of Central Nervous System Tumors (CNS) tumors. The sequelae often impair the function of the upper and lower extremities and manifest themselves as difficulties in gross and fine motor skills, which encompasses self care and walking. Overall, the five-year survival rate for children younger than 15 years with brain tumors is between 60 to 90 percent. Approximately two-thirds of survivors have long term neurological deficits. These neurologic deficits often manifest themselves as musculoskeletal abnormalities. It is essential to recognize the potential consequences of a CNS tumor and its associated treatments in an effort to prevent disability. Following the initial neurosurgical and oncologic treatment, the acute and chronic stages of the orthopaedic care for these patients differ significantly. Many of the rehabilitation and treatment principles for brain tumor patients have evolved from the principles used in stroke and traumatic brain injury. Orthopaedic treatment specifically includes preventing, identifying, and treating spasticity, contractures, bony and spinal deformities, and gait abnormalities.
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PMID:Orthopaedic issues in children and adolescents with central nervous system tumors. 2175 12

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis.
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PMID:Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis. 2694 90