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Aggrecan deficiency, due to heterozygous mutations in the <jats:italic>ACAN<\/jats:italic> gene, causes dominantly inherited short stature and, in many patients, early\u2010onset osteoarthritis and degenerative disc disease. We aimed to further characterize this phenotypic spectrum with an emphasis on musculoskeletal health. Twenty\u2010two individuals from nine families were enrolled. Histories and examinations focused on joint health, gait analysis, joint specific patient reported outcomes, and imaging studies were performed. All patients had dominantly inherited short stature, with the exception of a de novo mutation. Short stature was worse in adults versus children (median height \u22123.05 <jats:italic>SD<\/jats:italic> vs. \u22122.25 <jats:italic>SD<\/jats:italic>). <jats:italic>ACAN<\/jats:italic> mutations were not always associated with bone age advancement (median advancement +1.1\u2009years, range 0 to +2\u2009years). Children had subtle disproportionality and clinically silent joint disease\u201425% with osteochondritis dissecans (OD). Adults had a high prevalence of joint symptomatology\u2013decline in knee function, disability from spinal complaints, and lower physical activity on outcome measures. Osteoarthritis (OA) and OD was detected in 90% of adults, and orthopedic surgeries were reported in 60%. Aggrecan deficiency leads to short stature with progressive decline in height <jats:italic>SD<\/jats:italic>, mild skeletal dysplasia, and increasing prevalence of joint pathology over time. Optimal musculoskeletal health and quality of life can be attained with timely identification of pathology and intervention.<\/jats:p>","DOI":"10.1002\/ajmg.a.62639","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T07:14:05Z","timestamp":1641798845000},"page":"1193-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical phenotype and musculoskeletal characteristics of patients with aggrecan deficiency"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0859-5964","authenticated-orcid":false,"given":"Eirene","family":"Alexandrou","sequence":"first","affiliation":[{"name":"Division of Endocrinology University of Iowa Stead Family Children's Hospital  Iowa City Iowa USA"},{"name":"Department of Pediatrics University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dauber","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Children's National Hospital  Washington District of Columbia USA"},{"name":"Department of Pediatrics George Washington School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Tyzinski","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Hwa","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Andrew","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Children's National Hospital  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Elangovan","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gubanich","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery A.","family":"Taylor\u2010Haas","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Paterno","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Backeljauw","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1208"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546505280214"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910380602"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.12.001"},{"issue":"252","key":"e_1_2_9_6_1","first-page":"1","article-title":"Anthropometric reference data for children and adults: United States, 2007\u20102010","volume":"11","author":"Fryar C. 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