A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

Abstract

BackgroundStickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome.Case presentationA 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, −2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (−1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp).ConclusionsIn this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report

“…Type II collagen is a major component of the articular cartilage, which reduces articular friction and absorbs load pressure during movement. COL2A1 mutations have been associated with various human disorders, which are collectively termed type II collagenopathies and include spondyloepiphyseal dysplasia congenita, Kniest dysplasia, Stickler dysplasia, otospondylomegaepiphyseal dysplasia and spondyloepiphyseal dysplasia with premature onset arthrosis ( 23 – 26 ).…”

Unsuccessful tracheal intubation in a patient with Kniest dysplasia undergoing repeated general anesthesia: a case report

“…Perioperative airway assessment is particularly important in patients with congenital anomalies that may cause obstruction. Although collagenopathies are reportedly associated with impaired musculoskeletal development such as kyphoscoliosis, tracheomalacia, midface hypoplasia, and cleft palate [6], which are likely to induce difficult airway management, rapid development of airway edema during airway management has rarely been described. We previously reported the development of airway constriction after several trials of tracheal intubation in the present patient associated at the age of 6 years [4].…”

Extracellular Matrix Remodeling During Palate Development

“…Mutation of COL11A2 in human cause Stickler syndrome type 3 and Nance-Insley syndrome. 26,41 However, inactivation of Col11a2 in mice does not lead to cleft palate, although other clinical features such as hearing loss and abnormal skeleton development replicate the human phenotypes. 41,42 Glycoproteins Fibronectins (FN) Fibronectin (FN) is a glycoprotein with a high molecular weight of 230-270 KD.…”

“…17 In human, mutation of COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 cause a group of hereditary conditions known as Stickler syndrome I-V, respectively, characterized by high myopia, retinal detachment, hearing loss, midfacial underdevelopment, and cleft palate is only described in Stickler syndrome I-III (Table 1). [26][27][28][29][30][31][32] Type II collagen is the major extracellular matrix component of cartilage and essential for endochondral bone formation. 5 In the palate mesenchyme, only a few osteoblast precursors express Col II in the palatal mesenchyme.…”