To report a rare case of adolescent high myopia with rhegmatogenous retinal detachment (RRD) caused by Kniest Dysplasia. A 17-year-old boy with high myopia presented with 4-day progressive vision loss in his left eye. Ophthalmic examination revealed lattice degeneration in the right eye and RRD involving the macula in the left eye. Systemic evaluation revealed brachydactyly, restrictive ventilatory impairment, and spinal/pelvic anomalies. Whole exome sequencing identified a de novo heterozygous COL2A1 variant, confirming the diagnosis of Kniest Dysplasia, a severe type II collagenopathy. The right eye received prophylactic laser photocoagulation, while the left eye underwent scleral buckling. This study highlights the importance of ocular evaluation in the comprehensive management of systemic connective tissue diseases.

Kniest dysplasia is a severe form of type II collagenopathy caused by mutations in collagen II alpha 1 chain (COL2A1) gene. It can be diagnosed in early childhood based on the clinical findings of short stature, splayed epiphysis, narrowed joint spaces and platyspondyly associated with maxillofacial, ophthalmological, and otolaryngological complications. Missense mutations and small deletions owing to exon skipping in the triple-helical region of COL2A1 have been reported in most cases of Kniest dysplasia. We describe a female patient aged 39 years with difficulty in walking, back pain, and limited movement of the lower extremities. She had experienced neck pain during adolescence; however, it gradually decreased with age. She also showed markedly short stature (-4.37 SD), cleft palate, cataract, retinal detachment, and serous otitis media. Radiographic analyses revealed epiphyseal enlargement of the longitudinal bones, kyphoscoliosis, and flat vertebrae in the thoracolumbar spine. The cervical spinal bodies were fused but not at the age of 19 years. Genetic analysis revealed a novel heterozygous mutation, c.1266+2T>A, in intron 20 of COL2A1. In silico predictive tools indicated that this mutation was pathological. Exon-trapping assay showed that this splice mutation led to both intron retention and exon skipping in the triple-helical region. These clinical findings and genetic tests confirmed the diagnosis of Kniest dysplasia. The diagnosis of Kniest dysplasia is sometimes difficult based on clinical findings in adulthood owing to progressive skeletal changes. The current novel splice mutation in COL2A1 demonstrates both out-of-frame transcript and in-frame deletion in Kniest dysplasia.

Kniest dysplasia is a rare skeletal disorder, characterized by mild dysmorphic features, cleft palate, short stature, short limbs, prominent joints, restricted joint mobility, hearing impairment, and ocular manifestations such as high-degree myopia, retinal detachment, and cataract. Typical radiological findings include platyspondyly, coronal clefts, and dumbbell-shaped long tubular bones. Herein, we report on an 8-month-old boy who was referred to the pediatric genetic department due to narrow thorax and short extremities. He had mild dysmorphic features, cleft palate, narrow thorax, short extremities, and short stature. On radiographies, platyspondyly, hemivertebra, and dumbbell-shaped long tubular bones were detected. Clinical and radiological findings were consistent with Kniest dysplasia. Clinical exome sequencing was performed and revealed a heterozygous, pathogenic c.905C>T (p.Ala302Val) variant in the COL2A1 gene, confirming the initial clinical diagnosis. Kniest dysplasia is a very rare skeletal dysplasia, and an accurate clinical diagnosis is important to provide the best possible follow-up.

Heterozygous COL2A1 gene mutations are associated with type 2 collagenopathies, characterized by a wide, diverse, and overlapping clinical spectrum in related diseases. Our goal is to describe the clinical, radiological, and molecular findings of patients with COL2A1-related dysplasia and investigate the phenotype-genotype correlation. We also highlight the challenge of categorizing COL2A1-related diseases with similar clinical and radiological phenotypes. Six patients from five unrelated families presented with disproportionate short stature.delayed motor milestones, waddling gait, normal intelligence, and similar radiological features, including delayed epiphyseal ossification, epimetaphyseal changes, scoliosis, lordosis, and platyspondyly. All underwent whole exome sequencing. Demographic, clinical, laboratory, and radiological data were retrospectively obtained from hospital records. Segregation analysis was conducted using Sanger sequencing in all patients. Based on clinical, radiological, and molecular results, the six patients were categorized into kniest dysplasia, spondyloepiphyseal dysplasia congenita, and spondyloepimetaphyseal dysplasia Strudwick type. Four novel variants (c.1023+2T>C, p.Gly465Asp, p.Gly855Asp, p.Gly669Ala) were identified in the COL2A1 gene. Accurate classification of type 2 collagenopathies is vital to provide appropriate genetic counseling. Predicting extraskeletal manifestations and reducing morbidity through early diagnosis and treatment will significantly improve the quality of life for patients. The purpose of this GeneReview is to: 1.. Describe the clinical characteristics of type II collagen disorders; 2.. Provide an evaluation strategy to identify the genetic cause of a type II collagen disorder in a proband; 3.. Review the differential diagnosis of type II collagen disorders with a focus on genetic conditions; 4.. Review management of type II collagen disorders; 5.. Inform genetic counseling of family members of an individual with a type II collagen disorder.

Pathogenic single nucleotide variants (SNVs) found in the COL2A1 gene are associated with a broad range of skeletal dysplasias due to their impact on the structure and function of the Col2a1 protein. However, the molecular mechanisms of some nucleotide variants detected during diagnostic testing remain unclear. The interpretation of missense and splicing variants caused by SNVs poses a significant challenge for clinicians. In this work, we analyzed 22 splicing variants in the COL2A1 gene which have been found in patients with COL2A1-associated skeletal dysplasias. Using a minigene system, we investigated the impact of these SNVs on splicing and gained insights into their molecular mechanisms and genotype-phenotype correlations for each patient. The results of our study are very useful for improving the accuracy of diagnosis and the management of patients with skeletal dysplasias caused by SNVs in the COL2A1 gene.