Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen individuals with Costello syndrome underwent a complete history, physical examination, and medical record review. Medical history and record review were performed for two additional children with Costello syndrome. The POSNA Functional Health Outcome Questionnaire Baseline Assessment was completed by the parents of all 18 children. All the children were below the fifth percentile for height and all had ligamentous laxity. All children demonstrated delayed walking and none was able to run. Orthopaedic problems included tight heel cords, congenital vertical talus, planovalgus feet, hip subluxation, kyphosis, scoliosis, radial head subluxation, elbow flexion deformity, reduced shoulder range of motion, and limitation of overhead activity. Foot problems were most frequently encountered. Two children had no orthopaedic symptoms. All children with Costello syndrome had poor scores on the POSNA Functional Health Outcome Questionnaire. Orthopaedic problems are a significant part of Costello syndrome, and affected individuals should be evaluated and followed-up regularly by an orthopaedic surgeon.
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PMID:Costello syndrome: orthopaedic manifestations and functional health. 1249 52

Costello syndrome is characterised by dwarfism, unique cutaneous lesions, a distinct facial gestalt, and mental retardation. There have been no detailed reports of severe spinal deformities requiring surgical treatment as a complication of Costello syndrome. We report a case of a 10-year-old girl with progressive scoliosis associated with Costello syndrome. She underwent anterior release and posterior surgical correction and fusion from T5 to L2 using a third generation hook and rod system plus spinous process wiring. Congenital portal vein deficiency and coagulopathy were other major complications. At 15-month follow-up, the patient had good balance and no evidence of instrumentation failure.
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PMID:Severe scoliosis associated with Costello syndrome: a case report. 1720 May 44

Disorders of the Ras/mitogen-activated protein kinase (MAPK) pathway have an overlapping skeletal phenotype (e.g. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and neurofibromatosis type 1 (NF1) individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine-derived crosslinks of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Participants were individuals with Noonan syndrome (n = 14), Costello syndrome (n = 21), and cardiofaciocutaneous (CFC) syndrome (n = 14). Pyridinium crosslinks from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by high performance liquid chromatography. Three separate analyses of covariance were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. The Dpd and the Dpd/Pyd ratio were elevated (p < 0.0001) in all three conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis.
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PMID:Bone resorption in syndromes of the Ras/MAPK pathway. 2120

The Ras/MAPK signal transduction pathway is critical for the regulation of proliferation and differentiation of multiple cell types. Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in the NF1 gene resulting in an increased Ras signaling cascade. Subsequently, additional syndromes with some overlapping physical manifestations such as Noonan syndrome, Costello syndrome, and cardiofaciocutaneous (CFC) syndrome were also shown to be due in many cases to mutations in genes encoding for proteins interacting with the Ras/MAPK pathway. Although neurocutaneous manifestations have been considered hallmark features for these disorders, multiple organ systems including the musculoskeletal system are affected. Some of the overlapping musculoskeletal phenotypes include scoliosis, kyphosis, anterior chest wall anomalies, pes planus, osteopenia, and hand anomalies. However, there are also discordant skeletal phenotypes such as sphenoid wing dysplasia and tibial pseudarthrosis seen only in NF1. We provide an overview of the concordant and discordant musculoskeletal manifestations in the RASopathies.
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PMID:The musculoskeletal phenotype of the RASopathies. 2149 74

Costello syndrome is a rare genetic condition caused by heterozygous alterations in HRAS and characterized by multi-system abnormalities. Individuals with Costello syndrome usually present with severe feeding difficulties in infancy, short stature, coarse facial features, increased tumor risks, cardiac and neurological complications, intellectual disability and orthopedic complications. This study further defines the orthopedic manifestations affecting individuals with Costello syndrome. We studied 43 participants and performed medical records review, clinical examinations and orthopedic inquiry forms. In 23 participants, hip and or spinal imaging assessments were completed. Serial radiographs were analyzed when available. A total of 25 orthopedic manifestations were identified. Ten manifestations were seen in the majority of the participants: hypotonia (87%), ligamentous laxity (85%), scoliosis (63%), kyphosis (58%), characteristic hand deformities (85%), ulnar deviation of the wrist (63%), elbow (55%) and shoulder contractures (65%), tight Achilles tendon (73%), and pes planus (53%). Other characteristics of special note were hip dysplasia (45%), foot deformities requiring surgical intervention (38%) and osteopenia/osteoporosis (47%). We also studied the development of the hips and spine. Uni- or bilateral hip dysplasia was congenital in some, while it developed throughout childhood in others. Spinal involvement included scoliosis, kyphosis, lordosis, and curvature reversal (thoracic lordosis and lumbar kyphosis). Based on these findings, we recommend routine referral to an orthopedic surgeon as well as instituting screening protocols for hips and spine for individuals with Costello syndrome.
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PMID:Orthopedic manifestations and implications for individuals with Costello syndrome. 2381 56