{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:01:20Z","timestamp":1784602880816,"version":"3.55.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Geleophysic dysplasia represents an exceedingly uncommon autosomal recessive skeletal disorder marked by profound growth restriction, contractures affecting multiple joints, and cardiac valve abnormalities. The molecular foundation involves\n                    <jats:italic>ADAMTSL2<\/jats:italic>\n                    gene mutations disrupting extracellular matrix architecture. We document a 29-year-old Taiwanese woman followed longitudinally for 25 years, presenting with severe short stature measuring 141.2\u00a0cm, widespread joint contractures, thoracolumbar scoliosis, and distinctive gait abnormalities. Whole-exome sequencing identified compound heterozygous\n                    <jats:italic>ADAMTSL2<\/jats:italic>\n                    mutations: c.286C&amp;gt;T resulting in p. Arg96Trp and c.454_459del causing p. Cys152_Thr153del deletion. The clinical course revealed musculoskeletal deterioration alongside mild mitral valve involvement and os odontoideum. Bilateral glaucoma, consistent with previously reported ocular manifestations in geleophysic dysplasia, was diagnosed at age 26. Notably, recent ophthalmologic evaluation revealed keratoconus-like corneal ectasia with paradoxically increased central corneal thickness measuring 690\u2013693\u00a0\u03bcm bilaterally, substantially exceeding normal values of 520\u2013560\u00a0\u03bcm. This paradoxical corneal thickening, contrasting with the stromal thinning characteristic of classical keratoconus, represents a novel\n                    <jats:italic>ADAMTSL2<\/jats:italic>\n                    -related corneal phenotype. The patient maintained normal intellectual capacity despite physical limitations, contrasting with published early mortality rates approaching 33%. This extended clinical documentation establishes keratoconus-like corneal ectasia with paradoxical corneal thickening as a novel ophthalmologic manifestation in geleophysic dysplasia, while adding to prior reports of glaucoma in this condition. These findings emphasize the necessity for comprehensive ophthalmologic monitoring in\n                    <jats:italic>ADAMTSL2<\/jats:italic>\n                    -related disorders and supporting multidisciplinary management strategies.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1751809","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T22:10:06Z","timestamp":1769379006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Novel ADAMTSL2 compound heterozygous mutations in geleophysic dysplasia with bilateral glaucoma and keratoconus-like corneal ectasia"],"prefix":"10.3389","volume":"17","author":[{"given":"Chung-Lin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University","place":["Taipei, Taiwan"]},{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Medicine, Mackay Medical University","place":["New Taipei City, Taiwan"]},{"name":"Mackay Junior College of Medicine, Nursing and Management","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Kuang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"College of Medicine, Fu-Jen Catholic University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Ching","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Rong","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ting","family":"Lo","sequence":"additional","affiliation":[{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Medicine, Mackay Medical University","place":["New Taipei City, Taiwan"]},{"name":"Mackay Junior College of Medicine, Nursing and Management","place":["Taipei, Taiwan"]},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuan-Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"International Rare Disease Center, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Medicine, Mackay Medical University","place":["New Taipei City, Taiwan"]},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1136\/jmg.2010.087544","article-title":"Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia","volume":"48","author":"Allali","year":"2011","journal-title":"J. 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