Combination of osteogenesis imperfecta and type 1 diabetes mellitus

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder accompanied by increased bone fragility. Five types of OI are distinguished on the basis of phenotypic manifestations. OI type 1 is characterized by a reduced amount of normal type 1 collagen and is the mildest form. In addition to the fractures, course of disease can be accompanied by short stature, skeletal deformity and joint hypermobility. Although fracture risk decreases with age, such patients needs regular follow-up with an assessment of bone mineral density (BMD) and, if necessary, correction of therapy to improve the quality of life. Type 1 diabetes mellitus (T1DM) is associated with a decreased BMD, which is mostly attributed to insulin deficiency and hyperglycemia, which also increase the risk of fractures. Achieving and stable maintenance of glycemic targets is often challenging, but it is necessary to exclude hyperglycemia as a factor that further worsens the quality of bone. This paper describes a clinical case of an extremely rare combination of type 1 OI and T1DM, two diseases with a pronounced negative effect on bone tissue. The combination of these pathologies requires special management tactics for such patients to reduce the risk of developing new fractures.

Parathyroid hormone promotes maxillary expansion and reduces relapse in the repeated activation maxillary expansion rat model by regulating Wnt/β-catenin pathway

Background Constricted maxillary bone is a common skeletal deformity, which may lead to crowding and posterior crossbite. Mid-palatal suture expansion is often used to increase the maxillary width, but its skeletal effects are limited and tend to relapse, even with prolonged retention. We hypothesized that parathyroid hormone (PTH) may reduce the relapse of maxillary expansion. Methods We established a novel rat maxillary expansion model using palatal tubes with an insertable “W”-shaped spring which can be repeatedly activated. A total of 32 male healthy Wistar rats were randomly divided into six groups: the control group, the PTH group, the expansion group, the expansion + PTH group, the expansion + relapse group and the expansion + PTH + relapse group. All animals in the first 4 groups were killed after 10 days and the 2 relapse groups were killed after 15 days. The maxillary arch widths and histological staining were used to assess the expansion and relapse effects. The immunohistochemical staining, micro-CT, RT-qPCR and Western blot were used to evaluate the bone remodeling during expansion. Results The suture width was increased by the expansion device, and the repeated activation maxillary expansion rat model showed better expansion effects than the conventional model. PTH significantly promoted the expansion width and reduced the relapse ratio. Meanwhile, in the expansion + PTH group, histological and immunohistochemical staining showed that osteoblasts, osteoclasts, new cartilage and osteoid were significantly increased, micro-CT showed increased bone mass, and PCR and Western blot results confirmed up-regulation of RANKL, β-catenin, type II collagen and OCN. Conclusion The novel repeated activation maxillary expansion rat model has better effects than the conventional model. PTH enhances the maxillary expansion and reduces its relapse by regulating Wnt/β-catenin and RANKL pathways. PTH administration may serve as an adjunctive therapy in addition to mechanical expansion for treatment of maxillary constriction.

Mutated VWA8 Is Associated With Developmental Delay, Microcephaly, and Scoliosis and Plays a Novel Role in Early Development and Skeletal Morphogenesis in Zebrafish

Von Willebrand A domain-containing protein 8 (VWA8), also named KIAA0564, is a poorly characterized, mitochondrial matrix-targeted protein having a putative ATPase activity. VWA8 is comprising of ATPase-associated domains and a VWFA domain associated with ATPase activity inside the cell. In the present study, we describe a large consanguineous family of Saudi origin segregating a complex developmental syndrome in an autosomal recessive fashion. All the affected individuals exhibited severe developmental disorders. DNA from three patients was subjected to whole-exome sequencing followed by Sanger sequencing. VWA8 knock-down zebrafish morpholinos were used to study the phenotypic effect of this gene on zebrafish development. A homozygous missense variant [c.947A > G; p.(Asp316Gly)] was identified in exon 8 of the VWA8 gene, which perfectly segregated with the disease phenotype. Using zebrafish morpholino, we observed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism. This is the first homozygous variant identified in the VWA8 gene underlying global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations in humans. We provide genetic and molecular evidence using zebrafish morpholino for a homozygous variant in the VWA8 gene, associated with such a complex developmental syndrome in humans.

Using Swimming Speed as an Indicator of Malformation: A Practical Approach for Identification and Removal of Juvenile Seabass (Dicentrarchus labrax L., 1758) with Skeletal Deformity

Skeletal abnormalities in farmed fish are one of the main problems that negatively affect the production enterprises in terms of economic, biological and animal health. Fish with skeletal deformities in hatcheries are considered as non-economic individuals and are therefore detected and removed manually from the production tanks, which is a time consuming and laborious work for the facilities. Since the formation of abnormalities in the skeletal structure of the fish during the early growth period cause reduced swimming ability or speed that prevent fish to compete during feeding. Further, since deformed fish has no market value, even the share of a small amount of feed among deformed fish will reduce the feed conversion for the market targeted individuals within the culture tank that in terms may increase the production cost per fish. Therefore, in culture conditions it is important to remove the deformed fish from the tank environment by quickly determining those fellows at the early stage of growth. The present study evaluates the effects of water velocity on swimming behavior of juvenile seabass (Dicentrarchus labrax) and provides a solution for a rapid identification -and mechanical removal of deformed fish from the culture environment by using swimming speed slowdown -and behavioral differences as an indicator of deformation.

Carlos II of Spain, ‘The Bewitched’: cursed by aspartylglucosaminuria?

Carlos II of Spain (1661–1700), last of the Spanish Habsburgs, was known as The ‘Bewitched’ due to his multiple medical issues and feeble nature. He suffered from a range of ailments extending beyond the well-known Habsburg jaw, including developmental delay, intellectual disability, dysarthria, skeletal deformity, recurrent infections, epilepsy and infertility, among others. The Habsburg dynasty of Spain was characterised by marked inbreeding, and the male line died out with Carlos II. Various diagnoses have been proffered to explain Carlos II’s infirmity, though none have been full satisfactory to explain the full breadth of his ailments. As illustrated here, it may be that aspartylglucosaminuria, an autosomal recessively inherited lysosomal storage disorder, can account for both the characteristic facial features and the wide variety of other features exhibited by Carlos II.

Ohvira syndrome with left radial hemimelia: a rare association

Ohvira syndrome is rare complex anomaly consisting of uterus didelphys, unilateral ipsilateral obstructed hemivagina and ipsilateral renal agenesis. It typically presents with dysmenorrhea or pelvic pain shortly after menarche due to collection of secretions in the uterus. Reporting a case of 32 years unmarried nulligravida lady with complaints of pain abdomen since 20 days with history of similar complaints 15 years bac. Patient was on Inj. DMPA 2 years back. On examination upper limb skeletal deformity-left radial hemimelia present with a mass of 14-16 weeks gravid uterus on per abdomen examination. USG (February 2020), was suggestive of uterus didelphys bicollis with collection of 108 cc noted in the right uterine cavity with right kidney agenesis with obscured right ovary. Total abdominal hysterectomy with left salphingo-oopherectomy was done. Specimen features were suggestive of uterus didelphys bicornis bicollis with right uterus hematometra with right cervix blind with right sided blind vagina with features suggestive of Ohvira syndrome.

A case of severe open bite malocclusion with crowding and short roots treated by two-jaw surgery including four-piece LeFort I osteotomy

BackgroundAppropriate operations in severe anterior open bite (AOB) cases are extremely complicated to perform because of the multiple surgical procedures involved, difficulty of predicting posttreatment aesthetics and high relapse rate.Case reportWe herein report a 16-year-old girl with skeletal Class II, severe AOB malocclusion and crowding with short roots and aesthetic and functional problems. Four-piece segmental LeFort I osteotomy combined with a posterior horseshoe-like osteotomy was performed for maxillary intrusion, and sagittal split ramus osteotomy (SSRO) and genioplasty were performed for mandibular advancement. The malocclusion and skeletal deformity were significantly improved by the surgical orthodontic treatment. Functional and aesthetic occlusion with an improved facial profile was established, and no further root shortening was observed. Acceptable occlusion and dentition were maintained after a two-year retention period.ConclusionThis strategy of surgical orthodontic treatment with a complicated operative procedure might be effective for managing severe AOB malocclusion.

Osteogenesis Imperfecta: Mechanisms and signaling pathways connecting classical and rare OI types

Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous skeletal dysplasia characterized by bone fragility, growth deficiency and skeletal deformity. Previously known to be caused by defects in type I collagen, the major protein of extracellular matrix, it is now also understood to be a collagen-related disorder caused by defects in collagen folding, post-translational modification and processing, bone mineralization and osteoblast differentiation, with inheritance of OI types spanning autosomal dominant and recessive as well as X-linked recessive. This review provides the latest updates on OI, encompassing both classical OI and rare forms, their mechanism and the signaling pathways involved in their pathophysiology. There is a special emphasis on mutations in type I procollagen C-propeptide structure and processing, the later causing OI with strikingly high bone mass. Types V and VI OI, while notably different, are shown to be interrelated by the IFITM5 p.S40L mutation that reveals the connection between the BRIL and PEDF pathways. The function of Regulated Intramembrane Proteolysis has been extended beyond cholesterol metabolism to bone formation by defects in RIP components S2P and OASIS. Several recently proposed candidate genes for new types of OI are also presented. Discoveries of new OI genes add complexity to already-challenging OI management; current and potential approaches are summarized.