Journal article
Clinical phenotype and musculoskeletal characteristics of patients with aggrecan deficiency
American journal of medical genetics. Part A, Vol.188(4), pp.1193-1203
04/2022
DOI: 10.1002/ajmg.a.62639
PMID: 35001504
Abstract
Aggrecan is a proteoglycan within the physeal and articular cartilage. Aggrecan deficiency, due to heterozygous mutations in the ACAN gene, causes dominantly inherited short stature and, in many patients, early-onset osteoarthritis and degenerative disc disease. We aimed to further characterize this phenotypic spectrum with an emphasis on musculoskeletal health. Twenty-two 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 -3.05 SD vs. -2.25 SD). ACAN mutations were not always associated with bone age advancement (median advancement +1.1 years, range 0 to +2 years). Children had subtle disproportionality and clinically silent joint disease-25% with osteochondritis dissecans (OD). Adults had a high prevalence of joint symptomatology-decline 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 SD, 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.
Details
- Title: Subtitle
- Clinical phenotype and musculoskeletal characteristics of patients with aggrecan deficiency
- Creators
- Eirene Alexandrou - University of IowaAndrew Dauber - Children's NationalLeah Tyzinski - Cincinnati Children's Hospital Medical CenterVivian Hwa - Cincinnati Children's Hospital Medical CenterMelissa Andrew - Children's NationalHee Kim - Cincinnati Children's Hospital Medical CenterStacey Elangovan - Cincinnati Children's Hospital Medical CenterPaul Gubanich - Cincinnati Children's Hospital Medical CenterJeffery A Taylor-Haas - Cincinnati Children's Hospital Medical CenterMark Paterno - Cincinnati Children's Hospital Medical CenterPhilippe Backeljauw - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.188(4), pp.1193-1203
- DOI
- 10.1002/ajmg.a.62639
- PMID
- 35001504
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Endocrinology and Diabetes; Stead Family Department of Pediatrics
- Record Identifier
- 9984354004702771
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