COL9A1-related disorder with pectus carinatum, without epiphyseal dysplasia: case report and review of literature

TY - JOUR

T1 - COL9A1-related disorder with pectus carinatum, without epiphyseal dysplasia

T2 - case report and review of literature

AU - Olarewaju, Bukola A.

AU - Alexander, Erin R.

AU - Crowe, Monica M.

AU - Dandurand, Kristina

AU - Melville, David

AU - Shamoun, Fadi

AU - Osundiji, Mayowa A.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to International Skeletal Society (ISS) 2024.

PY - 2025/7

Y1 - 2025/7

N2 - COL9A1 encodes the alpha-1 chain of type IX collagen heterotrimer, which is a vital component of collagen fibrils in hyaline cartilage. There are preliminary lines of evidence suggesting that COL9A1 mutations may be associated with autosomal dominant multiple epiphyseal dysplasia (MED), a disorder affecting the epiphysis of long bones. With only 2 reported cases (both from the same family) of MED in autosomal dominant COL9A1-related disorders (MIM 614135) in the clinical scientific literature hitherto, the phenotype is poorly understood at present. Here, we report the clinical and imaging findings associated with a novel COL9A1 mutation in comparison to the previously reported cases. We studied a 22-year-old male, who presented with a chronic history of leg pain and laxity of the knee joint, in the context of a history of pectus carinatum requiring a chest brace, and tall stature (height = 186.9 cm) with bilateral piezogenic pedal papules. Gene panel testing and a radiographic skeletal survey were subsequently performed. Gene panel test showed a heterozygous pathogenic variant in the COL9A1 that is denoted as c.188del (p.Phe63Serfs*3) and is predicted to result in a loss-of-function. The patient’s long bones all appeared slender on a radiograph, without apparent epiphyseal dysplasia. Our findings suggest that the phenotypic spectrum of COL9A1-related disorders may potentially include other skeletal anomalies (such as pectus carinatum and slender appearance of long bones) aside from epiphyseal dysplasia.

AB - COL9A1 encodes the alpha-1 chain of type IX collagen heterotrimer, which is a vital component of collagen fibrils in hyaline cartilage. There are preliminary lines of evidence suggesting that COL9A1 mutations may be associated with autosomal dominant multiple epiphyseal dysplasia (MED), a disorder affecting the epiphysis of long bones. With only 2 reported cases (both from the same family) of MED in autosomal dominant COL9A1-related disorders (MIM 614135) in the clinical scientific literature hitherto, the phenotype is poorly understood at present. Here, we report the clinical and imaging findings associated with a novel COL9A1 mutation in comparison to the previously reported cases. We studied a 22-year-old male, who presented with a chronic history of leg pain and laxity of the knee joint, in the context of a history of pectus carinatum requiring a chest brace, and tall stature (height = 186.9 cm) with bilateral piezogenic pedal papules. Gene panel testing and a radiographic skeletal survey were subsequently performed. Gene panel test showed a heterozygous pathogenic variant in the COL9A1 that is denoted as c.188del (p.Phe63Serfs*3) and is predicted to result in a loss-of-function. The patient’s long bones all appeared slender on a radiograph, without apparent epiphyseal dysplasia. Our findings suggest that the phenotypic spectrum of COL9A1-related disorders may potentially include other skeletal anomalies (such as pectus carinatum and slender appearance of long bones) aside from epiphyseal dysplasia.

KW - Collagen

KW - Dysplasia

KW - Epiphyseal

KW - Pectus carinatum

UR - https://www.scopus.com/pages/publications/85211150402

U2 - 10.1007/s00256-024-04852-8

DO - 10.1007/s00256-024-04852-8

M3 - Article

C2 - 39636322

AN - SCOPUS:85211150402

SN - 0364-2348

VL - 54

SP - 1537

EP - 1541

JO - Skeletal Radiology

JF - Skeletal Radiology

IS - 7

M1 - 116169

ER -