Analysis of phenotypic manifestations of connective tissue dysplasia in adult patients with osteogenesis imperfecta and development of a diagnostic algorithm

Connective tissue dysplasia (CTD) is a genetically determined disorder of the development of connective tissue in the embryonic and postnatal periods, which is characterized by defects in the structure of the fibers and basic substance of the connective tissue, which can cause a variety of disorders in the functioning of the internal organs and the musculoskeletal system. Today, there are two main groups of CTD: differentiated (monogenic, hereditary) and undifferentiated (multifactorial). More than 250 hereditary variants of CTD have been described in the literature, one of which is osteogenesis imperfecta (OI), a disease characterized by frequent low-traumatic bone fractures, hear- ing impairment, pathology of tooth enamel, and blue coloration of the sclera of patients. However, data on the presence of other clinical manifestations of CTD, i. e. about the systemic involvement of connective tissue are fragmentary.

Aim of the study – to analyze the frequency of occurrence of phenotypic signs of connective tissue dysplasia in adult patients with osteogenesis imperfecta and to develop an algorithm for clinical diagnostics.

Materials and methods. A single-stage cross-sectional comparative study was conducted on 40 patients with osteogenesis imperfecta and 45 healthy controls at the Clinic of the Bashkir State Medical University. Joint hypermobility (JH) was determined using the Beighton scale; connective tissue dysplasia was assessed using a modified table by T.I. Kadurina. Bone mineral density was determined using X-ray densitometry.

Results. Statistically significant differences in the frequency of occurrence of phenotypic signs of CTD were revealed: temporomandibular joint crunching (р<0,001), dental enamel pathology (р<0,001), JH (p=1.4×10–4), kyphoscoliotic deformity of the spine (p=1.1×10–4), chest deformity (p=0.010), valgus feet (p=0.005), joint crunching (p=0.023), mitral valve prolapse (p=0.005) and arterial hypotension (p=0.021). Statistically significant differences in bone mineral density in absolute values (р<0,001) and Z-criterion levels (р<0,001) were also observed.

Conclusions. In patients with OI, statistically significantly more frequent phenotypic manifestations of CTD were revealed. For patients with type I OI, hemorrhagic manifestations are typical, as well as ptosis of internal organs. In type III, spinal deformities are characteristic, chest deformities were more often observed in patients with type V OI. A clinical algorithm for determining OI types was developed to optimize diagnostics and genotyping.

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