A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions

Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia.

Anesthesia for surgery in a patient with Knist's dysplasia for severe scoliotic deformity

Kniest dysplasia is a disease that is inherited in an autosomal dominant manner. It manifests itself as dwarfism, scoliotic deformity of the spine, impaired joint mobility, muscle weakness, visual impairment, and sensorineural deafness. As a result of disproportionate trunk shortening, lumbar hyperlordosis and kyphoscoliosis develop, leading to internal organs (respiratory, cardiovascular system) disorders, disability, and reduced life expectancy. A case of surgical treatment of a patient with Kniest dysplasia for severe kyphoscoliotic spinal deformity is described. Posterior corrective cross-rod transpediculocorporal screw spondylodesis T3-L5 with bone autoplasty was performed. While planning anesthesia, difficult tracheal intubation was evaluated on the LEMON scale of 7 points high-risk. While performing tracheal intubation, endoscopic techniques were used: videolaryngoscope, intubation bronchoscope, enabling success. Management of intraoperative blood loss was conducted by a complex of measures: laying the patient in the prone position with the release of the abdominal cavity, normothermia, intraoperative hemodilution of azlactone-balanced polyionic solutions to achieve the target hematocrit in the range of 24%26%, and controlled hypotension with blood pressure decreased by 30% from the original hardware blood reinfusion during surgery. Also, on the first postoperative day, fusing tranexamic acid, correcting anemia and deficiency of blood coagulation factors donor components contributed to the success. Discussion. When planning surgery and anesthesia, it is necessary to consider the risk of developing malignant hyperthermia, predicting difficult intubation, and complying with the algorithm to ensure airway patency and prevent massive intraoperative blood loss. With a comprehensive approach to patient management, it is possible to achieve rapid rehabilitation and discharge for outpatient treatment. Surgical treatment for rapidly progressing severe kyphoscoliathical spinal deformity can change the quality and duration of life in patients with Kniest syndrome.

Orthodontic Treatment in a Patient With Kniest Dysplasia: A Case Study and Review of Literature

Kniest dysplasia is a rare autosomal dominant chondrodysplasia that is characterized by distinct musculoskeletal and craniofacial irregularities. These craniofacial abnormalities include cleft palate, midface anomalies, tracheomalacia, and hearing loss. This article illustrates a case of Kniest dysplasia that presented for orthodontic treatment. The purpose of this literature review is to describe clinical manifestations, radiographic features, histopathological features, genetic mutation, and management of Kniest dysplasia.

Skeletal Dysplasias

This chapter reviews the more common viable skeletal dysplasias. The disorders discussed here include the less severe type II collagenopathies, spondyloepiphyseal dysplasia and Kniest dysplasia. The many types of chondrodysplasia punctata, both the environmental and genetic types are reviewed. Syndromes and disorders with vertebral abnormalities are enumerated including spondylothoracic dysplasia. Important metaphyseal dysplasias with immune dysfunction such as Cartilage-hair hypoplasia are covered as well a few of the skeletal ciliopathies including Jeune syndrome and Ellis Van Creveld syndrome. Diastrophic dysplasia and the underdiagnosed Three M syndrome are discussed. The clinical approach and testing strategies are reviewed. The clinical case presentation features an infant, born to a mother with mixed connective tissue disease, with chondrodysplasia punctata caused by transplacental passage of maternal autoantibodies

Spondyloepiphyseal Dysplasia Congenita and Related Type 2/Type 11 Collagen Disorders

This chapter further discusses bone dysplasias, and explores achondrogenesis II (hypochondrogenesis), platyspondylic dysplasia (Torrance type), spondyloepiphyseal dysplasia congenita, spondylo-epi-metaphyseal dysplasia (Strudwick type), Kniest dysplasia, spondyloepiphyseal dysplasia (Stanescu type), spondyloperipheral dysplasia, spondyloepiphyseal dysplasia with short metatarsals, Stickler dysplasia, fibrochondrogenesis, and oto-spondylo-megaepiphyseal dysplasia. Each discussion includes major clinical findings, major radiographic features, genetics, major differential diagnoses, and a bibliography.