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Case Reports
. 2022 Jan;10(1):e1773.
doi: 10.1002/mgg3.1773. Epub 2021 Dec 10.

Variable expressivity in a family with an aggrecanopathy

Antoine Denis  1 , Sami Chergui  1 , Shuaa Basalom  1 , Philippe M Campeau  1 , Chantal Janelle  1 , Thierry Pauyo  1
Affiliations
Case Reports

Variable expressivity in a family with an aggrecanopathy

Antoine Denis et al. Mol Genet Genomic Med. 2022 Jan.

Abstract

Background: Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic variants in the gene encoding Aggrecan; ACAN. Aggrecan, a proteoglycan, is an essential component of the articular and growth plate cartilage.

Methods: Herein, we report three individuals from one family; the proband who presented with short stature, a lower limb bone exostosis, and bilateral knee and elbow OCD at the age of 13 years old. His twin brother presented with isolated short stature and his father with short stature and lumbar disc herniation.

Results: Next-generation sequencing of the ACAN gene in the proband identified a frameshift variant which is also present in the brother and father with short stature. The proband was treated surgically with bilateral elbow microfracture, after the failure of conservative therapy.

Conclusion: To the best of our knowledge, this is the first patient with an aggrecanopathy who presents with osteochondritis dissecans due to a frameshift variant. This family presents with variable expressivity which might be attributed to modifier genes.

Keywords: aggrecan; aggrecanopathy; cartilage; chondrodysplasia; familial osteochondritis dissecans; osteochondritis dissecans; skeletal dysplasia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
3D illustration of the Agrrecan protein showing the different domains. The pathogenic variant (p. Phe1887Leufs*15) falls on the Chondroitin sulphate attachment domain 2 (CS2)
FIGURE 2
FIGURE 2
(a‐d) Radiographs of left and right elbow. (arrow) Osteochondral defects are observed bilaterally in capitellum as a radiolucent lesion without signs of fragmentation
FIGURE 3
FIGURE 3
Left elbow Coronal T2 MRI. (Arrow) 1,75 × 5.19 mm cartilage defect in the capitellum without surrounding edema or signs suggestive of instability
FIGURE 4
FIGURE 4
(a,b) Right elbow Coronal T2 MRI. (arrow) A 4.48 × 5.01 mm subchondral cyst in the capitellum. (Arrowhead) An osteochondral defect 14.67 × 15.01 mm is observed in the capitellum without surrounding edema and with a radio‐intense line in the fragment bed suggestive of instability. (ICRS Stage 3)
FIGURE 5
FIGURE 5
Right knee AP (a) and lateral radiographs (b). Small osteochondral fragment at the distal edge of the medial facet of the patella (Arrow)
FIGURE 6
FIGURE 6
Left knee AP (a) and lateral radiographs (b). Pedunculated osteochondroma on the posterior medial proximal tibia (Arrow) . There are no osteochondral lesions
See this image and copyright information in PMC

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