Clinical and Genetic Characteristics of COL2A1-Associated Skeletal Dysplasias in 60 Russian Patients: Part I

The significant variability in the clinical manifestations of COL2A1-associated skeletal dysplasias makes it necessary to conduct a clinical and genetic analysis of individual nosological variants, which will contribute to improving our understanding of the pathogenetic mechanisms and prognosis. We presented the clinical and genetic characteristics of 60 Russian pediatric patients with type II collagenopathies caused by previously described and newly identified variants in the COL2A1 gene. Diagnosis confirmation was carried out by new generation sequencing of the target panel with subsequent validation of the identified variants using automated Sanger sequencing. It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%). However, Stickler syndrome, type I was less common (17%). In the COL2A1 gene, 28 novel variants were identified, and a total of 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity, and were not found in Stickler syndrome, type I and Kniest dysplasia. In the C-propeptide region, five novel variants leading to the development of unusual phenotypes of spondyloepiphyseal dysplasia have been identified.

Determinants of complex regional pain syndrome type I in patients with scaphoid waist fracture- a multicenter prospective observational study

Background The aim of this prospective study was to assess the incidence of complex regional pain syndrome type I (CRPS I) in patients with scaphoid waist fracture and to explore associated factors. Methods This was a multicenter, prospective observational study. Demographic, imaging indicators and clinical data were collected before the conservative treatment of scaphoid waist fracture patients. The occurrence of CRPS I and pain condition were the main outcomes. To explore the factors associated with CRPS I, multivariate logistic regression model was used. Results A total of 493 scaphoid waist fracture participants undergoing conservative treatment were recruited for this study. The incidence of CRPS I was 20% (n = 87). The average time between injury and the onset of CRPS I was 6.7 ± 2.1 weeks. Multivariable logistic regression analysis revealed that female sex (odds ratio (OR): 1.669; 95% confidence interval (CI): 1.189–2.338), diabetes mellitus (OR: 3.206; 95% CI: 2.284–4.492), and severe pain condition before treatment (visual analog scale (VAS) score more than 4 cm) (OR: 27.966; 95% CI: 19.924–39.187) were independently associated with CRPS I. Conclusions Patients suffering from scaphoid waist fracture may be at a higher risk of CRPS I, especially in women with diabetes mellitus who report severe pain before treatment. Early screening and regular follow up evaluation are recommended in these patients.

Functional Outcomes After a Physiotherapy Program in Elderly Patients With Complex Regional Pain Syndrome Type I After Distal Radius Fracture: A Prospective Observational Study

Background: No published prospective studies have reported the clinical effects of physiotherapy at 1-year follow-up in patients with complex regional pain syndrome type I (CRPS I) after distal radius fracture (DRF). The purpose of this study was to evaluate at 1-year follow-up the functional effects of physiotherapy program in elderly patients with CRPS I after extra-articular DRF. Methods: A total of 72 patients with CRPS I after DRF were prospectively recruited. All patients were treated with a 6-week supervised physiotherapy treatment. Three evaluations were performed: at the beginning, at the end of the treatment, and at 1-year follow-up. Wrist function, upper limb function, grip strength, and pain intensity were assessed with the Patient-Rated Wrist Evaluation (PRWE), Disabilities of the Arm, Shoulder, and Hand (DASH), Jamar dynamometer, and Visual Analogue Scale (VAS), respectively. Results: At 1-year follow-up, the PRWE showed a decrease of 21.6 points (Cohen’s d = 2.8; 95% confidence interval [CI] = 18.6-24.6; P < .05); the DASH showed a decrease of 23.8 points (Cohen’s d = 2.9; 95% CI = 20.8-26.7; P < .05); grip strength showed an increase of 40.6% (Cohen’s d = 5.0; 95% CI = 43.5-37.6; P < .05); and the VAS showed a decrease of 2.6 cm (Cohen’s d = 1.9; 95% CI = 2.11-3.16; P < .05). Conclusion: At 1-year follow-up, a physiotherapy program showed clinically and statistically significant results in all functional outcomes in elderly patients with CRPS I after extra-articular DRF.

Diffusion Tensor Imaging of Auditory Pathway in Patients With Crigler-Najjar Syndrome Type I: Correlation With Auditory Brainstem Response

Aim: To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response. Methods: Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients. Results: There was significantly higher mean diffusivity of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls on both sides for all regions ( P = .001). The fractional anisotropy of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls was significantly lower, with P values of, respectively, .001, .001, .003, and .001 on the right side and .001, .001, .003, and .001 on left side, respectively. Also, a negative correlation was found between the maximum bilirubin level and fractional anisotropy of the left superior olivary nucleus and inferior colliculus of both sides. A positive correlation was found between the mean diffusivity and auditory brainstem response wave latency of the right inferior colliculus and left cochlear nucleus. The fractional anisotropy and auditory brainstem response wave latency of the right superior olivary nucleus, left cochlear nucleus, and inferior colliculus of both sides were negatively correlated. Conclusion: Diffusion tensor imaging can detect microstructural changes in the auditory pathway in Crigler Najjar syndrome type I that can be correlated with auditory brainstem response.

Autoimmune polyglandular syndrome type 1 and eye damage

Autoimmune polyendocrine syndrome type 1 (APS type 1) is a disease characterized by a variety of clinical manifestations resulting from the involvement of multiple endocrine and non-endocrine organs in the pathological process. APS type 1 is a rare genetically determined disease with autosomal recessive inheritance. Mutations in the autoimmune regulator gene (AIRE) lead to a disruption of the mechanism of normal antigen expression and the formation of abnormal clones of immune cells, and can cause autoimmune damage to organs. Within APS type 1, the most common disorders are primary adrenal insufficiency, hypoparathyroidism, and chronic candidiasis. Some understudied clinical manifestations of APS type 1 are autoimmune pathological processes in the eye: keratoconjunctivitis, dry eye syndrome, iridocyclitis, retinopathy, retinal detachment, and optic atrophy. This review presents the accumulated experimental and clinical data on the development of eye damage of autoimmune nature in APS type 1, as well as the laboratory and instrumental methods used for diagnosing the disease. Changes in the visual organs in combination with clinical manifestations of hypoparathyroidism, adrenal insufficiency and candidiasis should lead the clinical doctor to suspect the presence of APS type 1 and to examine the patient comprehensively. Timely genetic counselling will allow early identifi cation of the disease, timely prescription of appropriate treatment and prevention of severe complications.