{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T02:07:33Z","timestamp":1758161253895,"version":"3.44.0"},"reference-count":27,"publisher":"Mathematical Modelling and Numerical Simulation with Applications","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pediatr Genet"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transient receptor potential vanilloid 4 channel (TRPV4) gene mutations have been described in skeletal system and peripheral nervous system pathology. The case described here is a 9-year-old male child patient, born to a nonconsanguineous marriage with normal birth history who had difficulty in walking and stiffness of joints for the last 7 years, and progressive weakness of all four limbs and urine incontinence for 1 year following falls. Physical examination showed below-average weight and height and short trunk. Musculoskeletal examination revealed bony prominence bilaterally in the knee joints and contractures in knee and elbow joints with brachydactyly; muscle tone was increased, with brisk deep tendon reflexes. Skeletal survey showed platyspondyly with anterior beaking with metaphyseal dysplasia. Magnetic resonance imaging of the spine revealed atlantoaxial instability with hyperintense signal changes at a cervicomedullary junction and upper cervical cord with thinning and spinal canal stenosis suggestive of compressive myelopathy with platyspondyly and anterior beaking of the spine at cervical, thoracic and lumbar vertebrae. Exome sequencing revealed a heterozygous de novo variant c.2389G\u2009&gt;\u2009A in exon 15 of TRPV4, which results in the amino acid substitution p.Glu797Lys in the encoded protein. The characteristics observed indicated spondylometaphyseal dysplasia, Kozlowski type (SMD-K). The child underwent surgical intervention for compressive myelopathy by reduction of atlantoaxial dislocation with C1 lateral mass and C2 pars fusion using rib graft and fixation using screws and rods. To conclude, for any child presenting with progressive kyphoscoliosis, short stature, platyspondyly, and metaphyseal changes, a diagnosis of SMD-K should be considered and the patient and family should be advised to avoid spinal injuries.<\/jats:p>","DOI":"10.1055\/s-0041-1741424","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T18:42:22Z","timestamp":1641494542000},"page":"158-165","source":"Crossref","is-referenced-by-count":0,"title":["Compressive Myelopathy Secondary to TRPV4 Skeletal Dysplasia: Spondylometaphyseal Dysplasia, Kozlowski Type"],"prefix":"10.53391","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-0492","authenticated-orcid":false,"given":"Vykuntaraju K.","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varunvenkat M.","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varsha M.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhananjaya K.","family":"Vamyanmane","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay K.","family":"Shivappa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohih H.","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Deparment of Pediatrics, BGS Global Institute of Medical Sciences, Bengaluru, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurudatta B.","family":"Vishwanathan","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Bengaluru, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"31409","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pbiomolbio.2009.10.002","article-title":"The vanilloid transient receptor potential channel TRPV4: from structure to disease","volume":"103","author":"W Everaerts","year":"2010","journal-title":"Prog Biophys Mol Biol"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/jmg.2009.075358","article-title":"Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family","volume":"47","author":"J Dai","year":"2010","journal-title":"J Med Genet"},{"issue":"08","key":"ref3","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/ng.166","article-title":"Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia","volume":"40","author":"M J Rock","year":"2008","journal-title":"Nat Genet"},{"issue":"03","key":"ref4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ajhg.2009.01.021","article-title":"Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia","volume":"84","author":"D Krakow","year":"2009","journal-title":"Am J Hum Genet"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/ajmg.a.33414","article-title":"Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations","volume":"152A","author":"G Nishimura","year":"2010","journal-title":"Am J Med Genet A"},{"key":"ref6","first-page":"2769","article-title":"La dysostose spondylo-metaphysaire","volume":"75","author":"K Kozlowski","year":"1967","journal-title":"Presse Med"},{"issue":"02","key":"ref7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"L Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1749-6632.2010.05389.x","article-title":"Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system?","volume":"1192","author":"F Guilak","year":"2010","journal-title":"Ann N Y Acad Sci"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cmet.2008.08.002","article-title":"TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts","volume":"8","author":"R Masuyama","year":"2008","journal-title":"Cell Metab"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1002\/art.24799","article-title":"Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes","volume":"60","author":"M N Phan","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1073\/pnas.1319569111","article-title":"TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading","volume":"111","author":"C J O'Conor","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1750-1172-6-37","article-title":"TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families","volume":"6","author":"E Andreucci","year":"2011","journal-title":"Orphanet J Rare Dis"},{"issue":"21","key":"ref13","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1002\/ajmg.a.31941","article-title":"Metatropic dysplasia: clinical and radiographic findings in 11 patients demonstrating long-term natural history","volume":"143A","author":"P Kannu","year":"2007","journal-title":"Am J Med Genet A"},{"issue":"10","key":"ref14","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/ajmg.a.34192","article-title":"Axial spondylometaphyseal dysplasia: additional reports","volume":"155A","author":"S Suzuki","year":"2011","journal-title":"Am J Med Genet 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