Congenital Connective Tissue Disorders Research Articles

Prescription pattern and effectiveness of antihypertensive drugs in patients with aortic dissection who underwent surgery.

Background: Surgical patients with aortic dissection often require multiple antihypertensive drugs to control blood pressure. However, the prescription pattern and effectiveness of antihypertensive drugs for these patients are unclear. We aimed to investigate the prescription pattern and effectiveness of different classes of antihypertensive drugs in surgical patients with aortic dissection. Methods: Newly diagnosed aortic dissection patients who underwent surgery, aged >20years, from 1 January 2012 to 31 December 2017 were identified. Patients with missing data, in-hospital mortality, aortic aneurysms, or congenital connective tissue disorders, such as Marfan syndrome, were excluded. Prescription patterns of antihypertensive drugs were identified from medical records of outpatient visits within 90days after discharge. Antihypertensive drugs were classified into four classes: 1) β-blockers, 2) calcium channel blockers (CCBs), 3) renin-angiotensin system, and 4) other antihypertensive drugs. Patients were classified according to the number of classes of antihypertensive drugs as follows: 1) class 0, no exposure to antihypertensive drugs; 2) class 1, antihypertensive drugs of the same class; 3) class 2, antihypertensive drugs of two classes; 4) class 3, antihypertensive drugs of three classes; or 5) class 4, antihypertensive drugs of four classes. The primary composite outcomes included rehospitalization associated with aortic dissection, death due to aortic dissection, and all-cause mortality. Results: Most patients were prescribed two (28.87%) or three classes (28.01%) of antihypertensive drugs. In class 1, β-blockers were most commonly used (8.79%), followed by CCBs (5.95%). In class 2, β-blockers+CCB (10.66%) and CCB+RAS (5.18%) were the most common drug combinations. In class 3, β-blockers + CCB+RAS (14.84%) was the most prescribed combination. Class 0 had a significantly higher hazard of the composite outcome (HR, 2.1; CI, 1.46-3.02; p < 0.001) and all-cause mortality (HR, 2.34; CI, 1.56-3.51; p < 0.001) than class 1. There were no significant differences in hazards for rehospitalization associated with aortic dissection among classes. Conclusion: Among operated patients with type A aortic dissection, no specific type of antihypertensive drug was associated with a better outcome, whereas among those with type B aortic dissection, the use of β-blockers and CCBs was related to a significantly lower risk of the composite outcome.

Machine learning and artificial intelligence in the prediction, diagnosis and treatment of thoracic aortic diseases (literature review). Part 1

Despite their relatively low prevalence compared to cardiac valve lesions and coronary heart disease, thoracic aortic aneurysm and dissection are potentially fatal and represent serious public health problems. The indications for surgical treatment in most thoracic aortic diseases are predominantly based on the maximum aortic diameter in a particular area. Congenital connective tissue disorder, thoracic aortic anomalies (e.g., coarctation), family history of aneurysms, aortic dissections, and sudden deaths are considered as additional risk factors of aortic-related complications influencing the “stricter” indications and lowering the “threshold” aortic diameter. At the same time, a certain proportion of patients with aortic diseases develop aortic dissection and rupture in normal or near-normal thoracic aortic diameter in certain section. Many factors influence the development of aortic diseases and complications, and assessing the contribution to the aetiology and pathogenesis of each factor is difficult. Machine learning and mathematical modeling using artificial intelligence is an actively developing area of computer science, which also finds application in medicine, in particular in the study, diagnosis, and treatment of thoracic aortic aneurysms and dissections. This article discusses modern methods of data analysis, prediction of thoracic aortic aneurysms and dissections, treatment planning in thoracic aortic diseases, and prediction of complications using machine learning and artificial intelligence.

Machine learning and artificial intelligence in the prediction, diagnosis and treatment of thoracic aortic diseases (literature review). Part 2

Despite their relatively low prevalence compared to cardiac valve lesions and coronary heart disease, thoracic aortic aneurysm and dissection are potentially fatal and represent serious public health problems. The indications for surgical treatment in most thoracic aortic diseases are predominantly based on the maximum aortic diameter in a particular area. Congenital connective tissue disorder, thoracic aortic anomalies (e.g., coarctation), family history of aneurysms, aortic dissections, and sudden deaths are considered as additional risk factors of aortic-related complications influencing the “stricter” indications and lowering the “threshold” aortic diameter. At the same time, a certain proportion of patients with aortic diseases develop aortic dissection and rupture in normal or near-normal thoracic aortic diameter in certain section. Many factors influence the development of aortic diseases and complications, and assessing the contribution to the aetiology and pathogenesis of each factor is difficult. Machine learning and mathematical modeling using artificial intelligence is an actively developing area of computer science, which also finds application in medicine, in particular in the study, diagnosis, and treatment of thoracic aortic aneurysms and dissections. This article discusses modern methods of data analysis, prediction of thoracic aortic aneurysms and dissections, treatment planning in thoracic aortic diseases, and prediction of complications using machine learning and artificial intelligence.

Ehlers-Danlos Syndrome in Prosthodontics, Periodontology, and Implant Dentistry: A Systematic Review of the Literature

Ehlers-Danlos Syndrome (EDS) is one of the most common congenital connective tissue disorders, affecting the synthesis and production of collagen cells. The medical implications for joints, muscles, soft tissue, and blood circulation have been documented in the literature. Many oral manifestations are displayed in EDS patients, including gingival recession, lack of attached gingiva, early severe periodontitis, and dental anomalies and dental caries. However, the literature is limited and oftentimes contradictory, and therefore provides no consensus for guidelines regarding prosthodontic, periodontal, and implant treatment of patients with EDS. Therefore, the aim of this systematic review was to analyze the pertinent literature regarding prosthodontics, periodontology, and implant dentistry in EDS patients.

Connective tissue presentation in two families expands the phenotypic spectrum of PYROXD1 disorders.

Recessive variants in the oxidoreductase PYROXD1 are reported to cause a myopathy in 22 affected individuals from 15 families. Here, we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction. Proband AII:1 is compound heterozygous for the recurrent PYROXD1 variant Chr12(GRCh38):g.21452130A>G;NM_024854.5:c.464A>G;p.(N155S) and Chr12(GRCh38):g.21462019_21462022del;NM_024854.5:c.892_895del;p.(V298Mfs*4) and proband BII:1 is compound heterozygous for Chr12(GRCh38):g.21468739-21468741del;NM_024854.5:c.1488_1490del;p.(E496del) and Chr12(GRCh38):g.21467619del;NM_024854.5:c.1254+1del. RNA studies demonstrate c.892_895del;p.(V298Mfs*4) is targeted by nonsense mediated decay and c.1254+1delG elicits in-frame skipping of exon-11. Western blot from cultured fibroblasts shows reduced PYROXD1 protein levels in both probands. Testing urine from BII:1 and six individuals with PYROXD1 myopathy showed elevated levels of deoxypyridinoline, a mature collagen crosslink, correlating with PYROXD1-disorder severity. Urine and serum amino acid testing of the same individuals revealed no reportable changes. In contrast to PYROXD1 knock-out, we find no evidence for disrupted tRNA ligase activity, as measured via XBP1 splicing, in fibroblasts expressing PYROXD1 variants. In summary, we expand the clinical spectrum of PYROXD1-related disorders to include an overlapping connective tissue and myopathy presentation, identify three novel, pathogenic PYROXD1 variants, and provide preliminary evidence that elevated urine DPD crosslinks may provide a clinical biomarker for PYROXD1 disorders. Our results advocate consideration of PYROXD1 variants in the differential diagnosis for undiagnosed individuals presenting with a connective tissue disorder and myopathy.

Histopathologic Features of Skin Biopsies in Patients with Hereditary Alpha Tryptasemia

Hereditary alpha-tryptasemia (HaT) is a common genetic condition with replication of the gene encoding for alpha tryptase. The HaT phenotype may be associated with dysautonomia and congenital connective tissue disorders, such as hypermobility spectrum disorder (HSD). We examined the association between HaT and abnormalities of collagen and elastin deposition on skin biopsies of patients with HaT.

Reduced Bone Mass in Collagen Prolyl 4-Hydroxylase P4ha1 +/-; P4ha2 -/- Compound Mutant Mice.

ABSTRACTProper deposition of the extracellular matrix and its major components, the collagens, is essential for endochondral ossification and bone mass accrual. Collagen prolyl 4‐hydroxylases (C‐P4Hs) hydroxylate proline residues in the ‐X‐Pro‐Gly‐ repeats of all known collagen types. Their product, 4‐hydroxyproline, is essential for correct folding and thermal stability of the triple‐helical collagen molecules in physiological body temperatures. We have previously shown that inactivation of the mouse P4ha1 gene, which codes for the catalytic α subunit of the major C‐P4H isoform, is embryonic lethal, whereas inactivation of the P4ha2 gene produced only a minor phenotype. Instead, mice with a haploinsufficiency of the P4ha1 gene combined with a homozygous deletion of the P4ha2 gene present with a moderate chondrodysplasia due to transient cell death of the growth plate chondrocytes. Here, to further characterize the bone phenotype of the P4ha1 +/−; P4ha2 −/− mice, we have carried out gene expression analyses at whole‐tissue and single‐cell levels, biochemical analyses, microcomputed tomography, histomorphometric analyses, and second harmonic generation microscopy to show that C‐P4H α subunit expression peaks early and that the C‐P4H deficiency leads to reduced collagen amount, a reduced rate of bone formation, and a loss of trabecular and cortical bone volume in the long bones. The total osteoblast number in the proximal P4ha1 +/−; P4ha2 −/− tibia and the C‐P4H activity in primary P4ha1 +/−; P4ha2 −/− osteoblasts were reduced, whereas the population of osteoprogenitor colony‐forming unit fibroblasts was increased in the P4ha1 +/−; P4ha2 −/− marrow. Thus, the P4ha1 +/−; P4ha2 −/− mouse model recapitulates key aspects of a recently recognized congenital connective tissue disorder with short stature and bone dysplasia caused by biallelic variants of the human P4HA1 gene. Altogether, the data demonstrate the allele dose‐dependent importance of the C‐P4Hs to the developing organism and a threshold effect of C‐P4H activity in the proper production of bone matrix. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome.

Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet.

A contemporary approach to a young female patient with Loeys-Dietz syndrome and an uncomplicated type B aortic dissection: a case report

BackgroundAortic dissection is a relatively uncommon, but often catastrophic disease that requires early and accurate diagnosis. It often presents in patients with congenital connective tissue disorders. The current aortic surgical techniques are related with serious early and late complications. This case report emphasizes the importance of early diagnosis of aortic root dilatation and the risk of dissection, especially in patients with congenital connective tissue disorders. We present an alternative, contemporary and multidisciplinary approach based on the present state of knowledge.Case presentationWe present a rare case of a young female patient with Loeys-Dietz syndrome who was admitted with an uncomplicated aortic dissection (Stanford type B / DeBakey type III) and a dilated aortic root. After a period of close surveillance and extensive vascular imaging, thoracic endovascular aortic repair was deemed to be technically not possible. Medical treatment was optimized and our patient successfully underwent a personalised external aortic root support procedure (PEARS) as a contemporary alternative to existing aortic root surgical techniques.ConclusionsThis case highlights the importance of interdisciplinary approach, close follow-up and multimodality imaging. The decision to intervene in a chronic type B aortic dissection is still challenging and should be made in experienced centers by an interdisciplinary team. However, if an acute complication occurs, thoracic endovascular aortic repair TEVAR is the method of choice. In all cases optimal medical treatment is important. There is increasing evidence that personalized external aortic root support procedure PEARS is effective in stabilizing the aortic root and preventing its dilatation and dissection not only in patients with Marfan syndrome, but also in other cases of aortic root dilation of other etiologies. Moreover, many publications have reported the additional benefit of reduction or even eradication of aortic regurgitation by improving coaptation of the aortic valve leaflets in dilated aortas.

Clinical Features And Response To Treatment In Patients With Skin Biopsies Showing Congenital Connective Tissue Disorders

Clinical Features And Response To Treatment In Patients With Skin Biopsies Showing Congenital Connective Tissue Disorders

Anniversary of professor of internal medicine Eduard Zemtsovsky

The paper presents a short survey of medical, research and educational activity of professor Zemtsovsky. Edward Veniaminovich Zemtsovsky is an avowed authority in our country in diagnostics and treatment of congenital connective tissue disorders. He has coauthored the first Russian recommendations for congenital connective tissue disorders diagnostics and treatment. Nowadays professor Zemtsovsky continues active research and pedagogical activity. He is a merited example of outstanding professional course of life.

Deviation of paradigmatic mutations found in shprintzen-goldberg syndrome

Shprintzen-Goldberg (S-G) Syndrome known as rare congenital connective tissue disorder where craniosynostosis and marfanoid habitus found to be the usual presentation. Craniofacial dysmorphism with multi-organ involvement documented to be amongst prominent features of this syndrome. Case characteristics is five-month-old male infant with craniosynostosis, and motor developmental delay was evaluated for congenital connective tissue disorder. Dysmorphic craniofacial features like dolichocephaly, triangular forehead, ocular hypertelorism, micrognathia and retrognathia were noticed besides congenital umbilical hernia, empty scrotal sac, clinodactyly with long slender fingers, hyper-mobile joints, hypotonia. Subsequent investigations revealed normal male karyotype (46, XY) while genetic analysis depicted missense mutations in six different genes. Conventionally, mutation in SKI gene reported for its’ associated with S-G syndrome where dysregulation of TGF-β signaling was discussed as the primary reason. In the present case discussed here, it was found to have polygenic mutational association where few novel genetic mutations were seen.

Coracohumeral Ligament Reconstruction for Patients With Multidirectional Shoulder Instability

Coracohumeral ligament pathology arises from acute trauma, capsular thickening, or congenital connective tissue disorders within the glenohumeral joint. Recent studies have highlighted the significance of this pathology in multidirectional shoulder instability because insufficiency of the rotator interval has become increasingly recognized and attributed to failed shoulder stabilization procedures. The diagnosis and subsequent treatment of coracohumeral ligament pathology can be challenging, however, because patients usually present with a history of failed surgical stabilization and persistent laxity. At the time of presentation, most patients have undergone failed nonoperative treatments and are indicated for surgical intervention. One of the options for the treatment of coracohumeral ligament pathology is reconstruction. The purpose of this Technical Note is to describe our preferred surgical technique for the reconstruction of the coracohumeral ligament. Research was performed at the Steadman Philippon Research Institute.

Gait Deviations in Children With Osteogenesis Imperfecta Type I.

Osteogenesis imperfecta (OI) is a congenital connective tissue disorder often characterized by orthopaedic complications that impact normal gait. As such, mobility is of particular interest in the OI population as it is associated with multiple aspects of participation and quality of life. The purpose of the current study was to identify and describe common gait deviations in a large sample of individuals with type I OI and speculate the etiology with a goal of improving function. Gait analysis was performed on 44 subjects with type I (11.7±3.08 y old) and 30 typically developing controls (9.54±3.1 y old ). Spatial temporal, kinematic, and kinetic gait data were calculated from the Vicon Plug-in-Gait Model. Musculoskeletal modeling of the muscle tendon lengths (MTL) was done in OpenSim 3.3 to evaluate the MTL of the gastrocnemius and gluteus maximus. The gait deviation index, a dimensionless parameter that evaluates the deviation of 9 kinematic gait parameters from a control database, was also calculated. Walking speed, single support time, stride, and step length were lower and double support time was higher in the OI group. The gait deviation index score was lower and external hip rotation angle was higher in the OI group. Peak hip flexor, knee extensor and ankle plantarflexor moments, and power generation at the ankle were lower in the OI group. MTL analysis revealed no significant length discrepancies between the OI group and the typically developing group. Together, these findings provide a comprehensive description of gait characteristics among a group of individuals with type I OI. Such data inform clinicians about specific gait deviations in this population allowing clinicians to recommend more focused interventions. Level III-case-control study.

Модифицированный способ определения должных значений диаметра корня аорты в фокусе патологии аорты у лиц с дисплазией соединительной ткани

Enlargement of the aortic root of occurs in many cases with cardiovascular disease, including congenital connective tissue disorders (CCTD), especially its differentiated and undifferentiated forms (UCCTD). A common deficiency of the generally accepted methods for diagnosing an aortic root dilation may be that persons with CCTD and cardiovascular diseases of potentially having a broader aortic root diameter could be included in the reference groups. The purpose of our study was to develop a modified method for determining the normal aortic root diameter in group of individuals without CCTD and cardiovascular diseases. The study included 464 apparently healthy people, men and women aged 15 to 65 years. All patients underwent general clinical examination, echocardiography. On the basis of external and internal signs of CCTD, patients with UCCTD were identified - the UCCTD group (n = 208) and without this pathology - the main group (n = 256). The calculation of the normal aortic root diameter (NARD) was made in accordance with the methods of Roman M. J. et al. (1989) and Devereux R. B. et al. (2012). The upper limit values of NARD (UL NARD) were calculated according to the algorithms of Roman M. J. et al. (1989), Devereux R. B. et al. (2012), Campens L. et al. (2014). The data obtained in the main group was used to develop a modified method for the determination of NARD. The mean values by echocardiography and calculated values of the aortic root by modified method of this study were practically the same in the main group, whereas the mean value of NARD calculated by the methods of Roman M. J. et al. and Devereux R. B. et al. in this sample were significantly higher in relation to the listed values. As the NARD values, the UL NARD were significantly higher for all evaluated algorithms in comparison with the modified method. In the group of patients with UCCTD, 13 cases of aortic root dilation were found according to the method of Roman M. J., compared to 19 cases by the modified method. At the same time, 3 patients with aortic root enlargement by the mew method had 7 points of systemic involvement, thus corresponding to the Ghent criteria of Marfan syndrome. The methods of Campens L. and Devereux R. B. were less sensitive, revealing only 5 and 1 patients with aortic root dilatation, respectively. The results of the study demonstrate that, in order to obtain more reliable information on the condition of the root of the aorta and its proper values, the modified method obtained in the course of the study can be used. This method is more sensitive in detecting the enlargement of the aortic root in CCTD and in diagnosing syndromic CCTD.

Betaglycan (TGFBR3) up-regulation correlates with increased TGF-β signaling in Marfan patient fibroblasts in vitro.

Marfan syndrome (MFS), a congenital connective tissue disorder leading to aortic aneurysm development, is caused by fibrillin-1 (FBN1) gene mutations. Transforming growth factor beta (TGF-β) might play a role in the pathogenesis. It is still a matter of discussion if and how TGF-β up-regulates the intracellular downstream pathway, although TGF-β receptor 3 (TGFBR3 or Betaglycan) is thought to be involved. We aimed to elucidate the role of TGFBR3 protein in TGF-β signaling in Marfan patients. Dermal fibroblasts of MFS patients with haploinsufficient (HI; n=9) or dominant negative (DN; n=4) FBN1 gene mutations, leading to insufficient or malfunctioning fibrillin-1, respectively, were used. Control cells (n=10) were from healthy volunteers. We quantified TGFBR3 protein expression by immunofluorescence microscopy and gene expression of FBN1, TGFB1, its receptors, and downstream transcriptional target genes by quantitative polymerase chain reaction. Betaglycan protein expression in FBN1 mutants pooled was higher than in controls (P=.004) and in DN higher than in HI (P=.015). In DN, significantly higher mRNA expression of FBN1 (P=.014), SMAD7 (P=.019), HSP47 (P=.023), and SERPINE1 (P=.008), but a lower HSPA5 expression (P=.029), was observed than in HI. A pattern of higher expression was noted for TGFB1 (P=.059), FN1 (P=.089), and COL1A1 (P=.089) in DN as compared to HI. TGFBR3 protein expression in cells, both presence in the endoplasmic reticulum and amount of vesicles per cell, correlated positively with TGFB1 mRNA expression (Rs=0.60, P=.017; Rs=0.55, P=.029; respectively). TGFBR3 gene expression did not differ between groups. We demonstrated that activation of TGF-β signaling is higher in patients with a DN than an HI FBN1 gene mutation. Also, TGFBR3 protein expression is increased in the DN group and correlates positively with TGFB1 expression in groups pooled. We suggest that TGFBR3 protein expression is involved in up-regulated TGF-β signaling in MFS patients with a DN FBN1 gene mutation.

Insight into the Pathology of a COL1A1 Signal Peptide Heterozygous Mutation Leading to Severe Osteogenesis Imperfecta

Osteogenesis imperfecta or “brittle bone disease” is a congenital disorder of connective tissue causing the bone to break easily. Around 85–90% of cases are due to autosomal dominant mutations in the genes encoding type I collagen, the major organic component of bone. Genotype–phenotype correlations have shown that quantitative defects of collagen type I lead to mild OI, whereas structural defects show a wide clinical range from mild to perinatal lethal. This may partially be explained by the type of amino acid substitution and the relative location in the domain structure. To fully understand the variability of the clinical manifestation and the underlying pathomechanisms, further investigations are required. Here we provide the first biochemical characterization of a mutation at the signal peptide cleavage site of COL1A1, a domain not yet characterized. By steady-state analysis, we observed reduced production of collagen type I. Furthermore, by pulse-chase analysis we detected delayed secretion and partial intracellular retention of collagen I. In the cellular fraction, the electrophoretic migration was abnormal; however, secreted type I collagen showed a normal migration pattern. The intracellular retention of collagen I was confirmed by immunofluorescent staining. Moreover, transmission electron microscopy of cultured fibroblasts revealed enlargement of ER cisternae. These results further support the hypothesis that mechanisms interfering with ER integrity play an important role in the pathology of severe OI.

Hearing assessment in a rare case of Hajdu Cheney syndrome

&lt;p class="abstract"&gt;&lt;span lang="EN-IN"&gt;Hajdu Cheney syndrome is extremely rare autosomal dominant congenital disorder of connective tissue. It may occur due to spontaneous de novo mutation and mutation in NOTCH-2 gene identified recently. Most characteristic features include aero-osteolysis involving phalanges of both hands and feet, osteoporosis, deformities of skull, mandible, spine and other bones, kyphoscoliosis and bone fractures. Rarely in some affected individuals, it causes joint hypermobility, dental problems, hearing loss, heart defects, kidney abnormality like polycystic kidneys, excess body hair and recurrent infections in childhood. It affects many parts of body particularly bones. Treatment is symptomatic. In this case report, we present a case of 14 years male child with features of Hajdu Cheney syndrome with genetic predisposition. Patient presented to ENT clinic with complaint of hearing loss.&lt;/span&gt;&lt;/p&gt;

P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye.

Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connective tissue, manifesting as early-onset joint hypermobility, joint contractures, muscle weakness and bone dysplasia as well as high myopia, with evidence of clinical improvement of motor function over time in the surviving patient. Similar to P4ha1 null mice, which die prenatally, the muscle tissue from P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle basement membrane. Patients were compound heterozygous for frameshift and splice site mutations leading to reduced, but not absent, P4HA1 protein level and C-P4H activity in dermal fibroblasts compared to age-matched control samples. Differential scanning calorimetry revealed reduced thermal stability of collagen in patient-derived dermal fibroblasts versus age-matched control samples. Mutations affecting the family of C-P4Hs, and in particular C-P4H-I, should be considered in patients presenting with congenital connective tissue/myopathy overlap disorders with joint hypermobility, contractures, mild skeletal dysplasia and high myopia.

Multiorgan violations in connective tissue dysplasia in children. diagnostic and management standards. Russian draft recommendations

In October 2014 in Moscow at the XIII Russian Congress “Innovative Technologies in Pediatrics and Pediatric Surgery” was adopted the first part of the Russian recommendations “Congenital and multifactorial hereditary connective tissue disorders in children. Diagnostic algorithms. Tactics of treatment”. Multifactorial connective tissue dysplasia have a high prevalence in the population. We present the second part of the draft Guidelines dealing with multiple organ disorders in the connective tissue dysplasia. Despite the high level of modern molecular techniques, clarification of their nosology remains a distant prospect. Figuring out the incidence of connective tissue dysplasia hindered by the lack of common terminology, standardized diagnostic criteria, as well as the practical inaccessibility of modern molecular genetic techniques to identify the disease. In the first part of the Guidelines we could not find a place for all aspects of this complex issue, which bears an interdisciplinary approach. Later it was planned to develop recommendations for doctors of various specialties. During writing the second part it was taken into account the specialists and research teams from St Petersburg, Moscow, Tver, Omsk, Novosibirsk, Ivanovo, Chelyabinsk, Izhevsk, Orenburg, Smolensk, Petrozavodsk, Nalchik, Barnaul, Saratov, Rostov-on-Don, Voronezh, Stavropol, Yaroslavl. The core of the group works in active collaboration since 2008. The draft of the second part of the recommendation characterized especially multifactorial connective tissue dysplasia in infants, multiple organ disorders of the cardiovascular, respiratory, urinary system, gastrointestinal tract, hemostasis, nervous, musculoskeletal, upper respiratory tract and maxillodental apparatus. It sets out the course and tactics of various diseases with concurrent connective tissue dysplasia.