Congenital collagenopathies increased the risk of inguinal hernia developing and repair: analysis from a nationwide population-based cohort study.

Herein, we aimed to explore whether male patients with congenital collagen diseases had a higher risk of inguinal herniation than patients without these diseases. Data were retrospectively collected from the National Health Insurance Research Database of Taiwan. The study cohort included 1,801 male patients diagnosed with congenital collagen diseases based on the ICD-9 CM diagnostic codes; after propensity score matching, the control group comprised 6,493 men without congenital collagen diseases. The primary endpoint was inguinal hernia repair during the observation period. During a median follow-up period of 133.9 months, the risk of inguinal herniation in the collagen group was significantly higher than that in the control group (HR = 2.237, 95% CI 1.646-3.291, p < 0.001). This phenomenon was observed in patients younger than 18 years (HR: 3.040, 95% CI 1.819-5.083, p < 0.001) and in those aged 18-80 years (HR: 1.909, 95% CI 1.186-3.073, p < 0.001). Asian men with congenital collagen diseases are at a high risk of developing inguinal hernias, regardless of age. Detailed physical examination and patient education should be performed for these patients to prevent inguinal herniation.

Artralgias e hiperlaxitud articular en mujer con oftalmopatía y sordera precoz / Arthralgias and articular hyperlaxitude in women with ophthalmopathy and early deafness

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Malformação venosa associada a hiperelasticidade cutânea e atrofia do tecido subcutâneo / Venous malformation associated with skin hyperelasticity and subcutaneous atrophy

A rigidez da parede venosa pode aumentar em síndromes em que há uma redução da quantidade de elastina, ocasionando malformações venosas mesmo em indivíduos que possuem mosaicismo para tais síndromes. Casos com apresentação de afecções colagenosas em áreas delimitadas não foram descritos na literatura. O paciente apresentava lesão bem delimitada em região anteromedial da coxa com aumento de elasticidade e presença de vasos tortuosos apenas no local da lesão, não apresentando nenhuma síndrome colagenosa. Foi realizada uma biópsia que evidenciou alterações em relação ao padrão das fibras elásticas e proliferação de vasos sanguíneos. A malformação venosa foi tratada satisfatoriamente com embolização. As doenças do colágeno causam hiperextensibilidade cutânea, o que provoca flacidez e propicia traumas. As colagenoses bem delimitadas são raras, pois geralmente esse grupo de doenças envolve acometimento sistêmico. As malformações vasculares podem ocorrer em diversas doenças do colágeno, mas de forma generalizada e não localizada, e uma explicação para isso seria o mosaicismo genético.

In syndromes that involve reduced quantities of elastin, the rigidity of vein walls may be increased, causing venous malformations, even in people who have mosaicism for these syndromes. There are no previous descriptions in the literature of collagen diseases presenting in specific, delimited areas. The patient described here presented with a lesion restricted to a well-defined area of the anteromedial thigh, in which elasticity was increased and vessels were tortuous, in the area of the lesion only, and with no other signs of collagen syndromes. A biopsy was conducted and the findings included changes to the normal arrangement of the elastic fibers and proliferation of blood vessels. The venous malformation was treated satisfactorily by embolization. Collagen diseases can cause cutaneous hyperextensibility, provoking flaccidity and a propensity to traumatisms. Connective tissue diseases restricted to well-delimited areas are rare, since this group of diseases usually has systemic involvement. Vascular malformations can be seen in many different collagen diseases, but with generalized rather than localized presentation. One possible explanation for the case described here is genetic mosaicism.

Autosomal recessive myosclerosis myopathy is a collagen VI disorder.

OBJECTIVE: To determine the clinical and molecular features of a new phenotype related to collagen VI myopathies. METHODS: We examined two patients belonging to a consanguineous family affected by myosclerosis myopathy, screened for mutations of collagen VI genes, and performed a detailed biochemical and morphologic analysis of the muscle biopsy and cultured fibroblasts. RESULTS: The patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. The truncated chain associated with the other two chains, giving rise to secreted collagen VI. Monomers containing the truncated chain were assembled into dimers, but tetramers were almost absent; secreted collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts. Mutated collagen did not correctly localize in the basement membrane of muscle fibers and was absent in the capillary wall. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, and increased number of pericytes. CONCLUSIONS: This familial case has the characteristic features of myosclerosis myopathy and carries a homozygous COL6A2 mutation responsible for a peculiar pattern of collagen VI defects. Our study demonstrates that myosclerosis myopathy should be considered a collagen VI disorder allelic to Ullrich congenital muscular dystrophy and Bethlem myopathy.

Larsen syndrome--lethal variety.

Larsen syndrome is a condition characterized by generalized defect in collagen formation. Autosomal dominant, autosomal recessive and even sporadic fresh mutations have been reported. Very few cases of lethal variety of Larsen syndrome have been reported in the world. The authors emphasize the importance of recognition of this condition which is often misdiagnosed.

[Congenital diseases of the aorta]. / Enfermedades congénitas de la aorta.

Congenital diseases of the aorta may be divided into three main groups. The most common group includes diseases which obstruct blood flow to the distal circulatory system. The second category includes those diseases which obstruct either the trachea or the esophagus. A third category of congenital diseases of the aorta includes abnormalities of the mechanical composition of the aorta. The major clinical manifestations included in each of these groups will be discussed.

Ocular and cutaneous manifestations of heritable disorders of collagen and elastic tissue.

Ocular and cutaneous stigmata are hallmarks of the heritable disorders of collagen and elastic tissue. Awareness of the oculocutaneous features is essential both to aid diagnosis and to direct management of affected patients. Although the angioid streaks of PXE, blue sclerae of OI, ocular fragility of EDS and ectopia lentis of Marfan syndrome are the best-known ocular signs of these disorders, other relevant ophthalmologic symptoms often accompany such classic findings.

Collagenopathic cardiopathies.

Collagenopathic cardiopathies are a subject of extreme etiologic, pathogenetic and clinical interest. These disorders are associated with congenital or acquired anomalies of the connective tissue and because of the diffusion and nearly total distribution of this tissue, have a higher frequency than what has been previously estimated. The collagenopathic cardiopathies, can be divided into two main groups: one deriving from hereditary connective tissue diseases, and the other from acquired connective tissue diseases. The first group has a Mendelian type of transmission whereas the other appears to be secondary to various kinds of stimuli (viral, immunologic etc.) although polygenic factors are present. Of the first group we considered Marfan's syndrome, the Ehlers-Danlos syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, cutis laxa and the diseases of the fundamental substance with particular reference to mucopolysaccharidosis type 1H (Hurler's syndrome). In all of these disorders a specific metabolic disturbance is responsible for the cardiovascular damage which is expressed, depending on the specific genetic component in a more or less serious form. Among the acquired diseases of the connective tissue, we examined rheumatoid arthritis, systemic lupus erythematosus, polydermatomyositis, scleroderma; of the reactive arthritis, rheumatic fever; of the seronegative forms, spondyloarthritis, ankylosing spondylitis and Reiter's syndrome, mixed connective tissue disease and Lyme's disease. It must be emphasized that all of these disorders share relatively common pathogenetic characteristics which point to the importance of the presence of various types of antigens, immune complexes and the significant role of some of the histocompatibility antigens, as well as possible disturbances of cell-mediated immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Patient with multiple congenital anomalies and decreased production and processing of procollagen in cultured fibroblasts.

We report on a patient with hip and elbow dislocations, joint hyperextensibility, peculiar facial appearance, torticollis, cryptorchidism, unilateral hexadactyly, and other minor anomalies. Cultured cells from this patient produce less type I procollagen and have a slower rate of processing of type I procollagen to collagen in the culture medium. We think that the pattern of clinical anomalies constitutes a previously unreported syndrome with type I procollagen defect as a manifestation of the syndrome.

Inheritance of vertical fiber hide defect in cattle.

Inheritance of vertical fiber hide defect (VFHD), a structural defect in collagen fiber orientation that causes weakness and reduced value of leather, was examined using histological data on hide biopsies obtained from 465 Hereford cattle by 65 sires. The data set included 44 offspring-dam pairs, for which VFHD phenotypes had been diagnosed on both the offspring and dam. Examination of offspring and parental frequency distributions indicated that inheritance of the condition was likely to be due to an autosomal recessive. In a subsequent experiment, a Hereford bull with a known VFHD phenotype was mated to Hereford cows with known VFHD phenotypes and to Angus cows not showing the defect. Angus were chosen because the defect has never been observed in the breed. All offspring (5) resulting from VFHD X VFHD matings expressed the defect, while no offspring (12) out of VFHD X non-VFHD matings (Angus cows) expressed the defect. It was concluded that VFHD is inherited as an autosomal recessive. The role that selection and alternative crossbreeding systems can play reducing phenotypic frequency of the defect is discussed.

Concepts in collagen biochemistry: evidence that collagenopathies underlie osteogenesis imperfecta.

Collagen, the principal structural macromolecule of the body, is expressed as a family of genetically distinct protein molecules. Two main subfamilies are emerging, the interstitial, fibrillar collagens (Types I, II and III) and the cell-associated or basement membrane collagens (Types IV and V). All types are synthesized as precursor molecules of procollagen, which are trimmed by specific proteases to form the subunit of extracellular fibrils. Evidence is accumulating that the osteogenesis imperfecta group of diseases are inherited molecular pathologies of Type I collagen, the commonest collagen type. However, a variety of biochemical lesions are anticipated, in part because of the marked clinical heterogeneity of the disorder. For example, in one variant a defect is becoming evident in the primary structure of Type I procollagen which seems to inhibit its rate of secretion from the cell. In another, there is evidence of complete failure to express the collagen alpha 2 chain, a disorder perhaps analogous to the thalassemia syndromes of hemoglobin pathology.

[The biochemistry of collagen and the locomotor apparatus. Hereditary diseases of connective tissue and rheumatologic diseases (part 2)]. / Biochimie du collagène et appareil locomoteur. Maladies héréditaires du tissu conjonctif et affections rhumatologiques (2e partie)

In lathyrism, the toxic agent directly blocks the development of the transverse links in the collagen fibre, while in bovine dermatosparaxis there is a deficiency of procollagen peptidase. Of the many clinical forms of the Ehlers-Danlos syndrome, some are due to a deficiency of lysine oxidase, others to deficiency of lysine hydroxylase and still others to procollagen peptidase deficiency. The essential deficiency in Marfan's disease is still unknown, but that in homocystinuria causes blocking of the groups necessary to form the transverse links. In osteogenesis imperfecta, which is probably a heterogeneous group, there is deficient consolidation of the collagen fibrils, the cause of which is still unknown. One possibility is a quantitative imbalance between chains of different types. In scleroderma there is excessive synthesis of an apparently normal connective tissue; the cause of this is also still unknown.