{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:06:55Z","timestamp":1791032815241,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T00:00:00Z","timestamp":1317340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dominant mutations in the receptor calcium channel gene <jats:italic>TRPV4<\/jats:italic> have been associated with a family of skeletal dysplasias (metatropic dysplasia, pseudo\u2010Morquio type 2, spondylometaphyseal dysplasia, Kozlowski type, brachyolmia, and familial digital arthropathy) as well as with dominantly inherited neuropathies (hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy). While there is phenotypic overlap between the various members of each group, the two groups were considered to be totally separate with the former being strictly a structural skeletal condition and the latter group being confined to the peripheral nervous system. We report here on fetal akinesia as the presenting feature of severe metatropic dysplasia, suggesting that certain <jats:italic>TRPV4<\/jats:italic> mutations can cause both a skeletal and a neuropathic phenotype. Three cases were detected on prenatal ultrasound because of absent movements in the second trimester. Case 4 presented with multiple joint contractures and absent limb movements at birth and was diagnosed with \u201cfetal akinesia syndrome\u201d. Post\u2010interruption and post\u2010natal X\u2010rays showed typical features of metatropic dysplasia in all four. Sequencing of the <jats:italic>TRPV4<\/jats:italic> gene confirmed the presence of de novo heterozygous mutations predicting G78W (Case 1), T740I (Cases 2 and 3), and K276E (Case 4). Although some degree of restriction of movements is not uncommon in fetuses with skeletal dysplasia, akinesia as leading sign is unusual and suggests that certain <jats:italic>TRPV4<\/jats:italic> mutations produce both chondrodysplasia and a peripheral neuropathy resulting in a severe \u201coverlap\u201d phenotype. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.34268","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T20:50:06Z","timestamp":1317415806000},"page":"2860-2864","source":"Crossref","is-referenced-by-count":34,"title":["Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy?"],"prefix":"10.1002","volume":"155","author":[{"given":"Sheila","family":"Unger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehart","family":"Lausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Stanzial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Gillessen\u2010Kaesbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Stefanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Maria","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Dionisi\u2010Vici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Nilius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Zabel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Superti\u2010Furga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.508"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-37"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.01102.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181ffe4bb"},{"key":"e_1_2_6_6_1","article-title":"TRVP4\u2010pathy manifesting both skeletal dysplasia and peripheral neuropathy","author":"Cho T\u2010J","year":"2011","journal-title":"Am J Med Genet"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.37"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.075358"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.509"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.237685"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.021"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.512"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019533"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33414"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.166"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33909"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/383094"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.34268","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.34268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:13:25Z","timestamp":1697613205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.34268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,30]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1002\/ajmg.a.34268"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.34268","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,30]]}}}