Aggrecanopathies: Report of a Spondyloepiphyseal Dysplasia Kimberley type (SEDK) in a family, caused by a previously undescribed likely pathogenic variant of the ACAN gene

Authors:

Enrique Daniel Austin-Ward1, Jean Villegas2

The study of patients with short stature is complex and requires diagnostic algorithms in which the evaluation by Genetics is essential, seeking to rule out genetic syndromes that may explain the patient’s manifestations. Among these possible causes, skeletal dysplasias should always be considered as a diagnostic possibility. We present the case of a family in which in the proband and in his progenitor a previously undescribed probably pathogenic variant was detected in the ACAN gene which encodes the Aggrecan Proteoglycan (PG), a fundamental component in the endochondral bone growth and in the articular cartilage, and whose alteration in heterozygous state produces Kimberley type Skeletal Spóndyloepiphyseal Dysplasia (SEDK) and other disorders known as aggrecanopathies. Molecular genetic analyses are becoming mandatory studies to achieve an accurate diagnosis in these cases. It is expected that the study of these conditions will shed light for a better understanding of the pathophysiology of osteoarthritis and for the development of new treatments for its management, given its high prevalence in older adults and the fact that aggrecan degeneration plays a central role in it.