Association between Kniest dysplasia and chondrosarcoma in a child.
Constitutive COL2A1 mutations are associated with a wide variety of clinical manifestations known as type II collagenopathies. Among them is Kniest dysplasia, which is phenotypically variable and includes both skeletal (short trunk and limbs, kyphoscoliosis, prominent joints, and osteoarthritis) and craniofacial characteristics. Kniest dysplasia mutations primarily arise in the triple-helicoidal region of the alpha 1 (II) chain in COL2A1 between exons 12 and 24. Somatic COL2A1 mutations have been identified in chondrosarcoma, a rare cartilage forming neoplasm, with a hypermutability of the gene reported in 37% of cases. However, to the best of our knowledge, there is no reported increase in predisposition to chondrosarcoma in human collagenopathies, and no reported clinical association between these congenital diseases and cartilaginous tumors. In the case study presented here, we report the first description of an association between these two rare diseases involving COL2A1, in a child presenting with Kniest dysplasia and a grade I sphenoethmoidal chondrosarcoma. We also describe a new constitutive mutation in COL2A1.
Pediatric Oncology Unit, Oscar Lambret Center, Lille, France.
Audrey
A
Hochart
Department of Clinical Genetic, Lille University Hospital, Lille, France.
Anne
A
Dieux
Department of Medical Genetic, Ghent University Hospital, Ghent, Belgium.
Paul
P
Coucke
Department of Pediatric Orthopedic Surgery, Lille University Hospital, France.
Damien
D
Fron
Department of Otolaryngology-Head and Neck Surgery, Lille University Hospital, Lille, France.
Pierre
P
Fayoux
Department of Ophthalmology, Lille University Hospital, Lille, France.
Pierre
P
Labalette
Department of Pediatric Radiology, Lille University Hospital, Lille, France.
Nathalie
N
Boutry
Biochemistry and Molecular Biology Department, Lille University Hospital, Lille, France.
Fabienne
F
Escande
Department of Neuropathology, Biology and Pathology Center, Lille University Hospital, Lille, France.
Sébastien
S
Aubert
Department of Neuropathology, Biology and Pathology Center, Lille University Hospital, Lille, France.
Florence
F
Renaud
Department of Radiology, Oscar Lambret Center, Lille, France.
Nathalie
N
Rocourt
Department of Pediatric Neurosurgery, Lille University Hospital, Lille, France.
Matthieu
M
Vinchon
Pediatric Oncology Unit, Oscar Lambret Center, Lille, France.|Unité Tumorigénèse et Résistance aux Traitements, INSERM U908, Oscar Lambret Center, Lille, France.
Pierre
P
Leblond
D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D003095:Collagen Diseases / Q000235:genetics* / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics*; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology; D005145:Face / Q000002:abnormalities* / Q000473:pathology; D006801:Humans; D006819:Hyaline Membrane Disease / Q000235:genetics* / Q000473:pathology; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
C499177:COL2A1 protein, human; D024043:Collagen Type II
COL2A1 gene; Kniest dysplasia; chondrosarcoma; pediatric