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Diabetes, Obesity & Metabolism Apr 2024Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as... (Review)
Review
Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.
Topics: Humans; Bardet-Biedl Syndrome; Diabetes Mellitus, Type 2; Kidney; Hyperphagia; Weight Loss
PubMed: 38302651
DOI: 10.1111/dom.15480 -
JPRAS Open Mar 2024Congenital thumb duplication is estimated to occur between 0.08 and 7.6 times per 1,000 live births; however its cause is still undetermined. In this report, we present...
Congenital thumb duplication is estimated to occur between 0.08 and 7.6 times per 1,000 live births; however its cause is still undetermined. In this report, we present a case of Wassel type VI thumb polydactyly. clinical examination revealed an optimal functional position and an aesthetically pleasing shape of the ulnar thumb as well as a superior nail and pulp. However, preoperative X-ray indicated a well formed carpometacarpal joint of the radial thumb compared to an underdeveloped CMC joint of the ulnar thumb. Through surgical procedure we combined the best parts of both thumbs with on-top plasty to achieve the most optimal outcome. In conclusion, it is important to determine an adequate treatment strategy for a patient based on both clinical and radiological assessments.
PubMed: 38293284
DOI: 10.1016/j.jpra.2023.12.007 -
Animal Genetics Apr 2024Polydactyly is a genetic abnormality that affects both pig welfare and industry profits. Despite efforts to explore the genetic basis of pig polydactyly, progress...
Polydactyly is a genetic abnormality that affects both pig welfare and industry profits. Despite efforts to explore the genetic basis of pig polydactyly, progress remains limited. In this study, we analyzed a group of Large White pigs with postaxial polydactyly, including 29 cases and 79 controls from 24 families. High-depth sequencing was performed on 20 pigs, while low-depth sequencing was improved through imputation for the remaining pigs. A genome-wide association study (GWAS) and genetic differentiation were conducted using the resequencing dataset, resulting in the identification of 48 significantly associated SNPs and 27 candidate regions. The genetic differentiation regions on chromosomes 5 and 18, which harbored GWAS-identified SNPs, were delineated as confidence regions. The confidence region at Chr18: 1.850-1.925 Mb covers the fifth intron of LMBR1, a gene that contains an important regulatory element for SHH, known as ZRS. Mutations in this ZRS have been found to cause polydactyly in animals and humans. Therefore, we propose LMBR1 as a prospective candidate gene for postaxial polydactyly. These findings emphasize the importance of exploring the role of ZRS within LMBR1 in the pathogenesis of polydactyly in pigs.
Topics: Humans; Animals; Swine; Genome-Wide Association Study; Polydactyly; Fingers; Mutation; Swine Diseases; Toes
PubMed: 38282540
DOI: 10.1111/age.13399 -
Traffic (Copenhagen, Denmark) Jan 2024Ciliary transport in eukaryotic cells is an intricate and conserved process involving the coordinated assembly and functioning of a multiprotein intraflagellar transport... (Review)
Review
Ciliary transport in eukaryotic cells is an intricate and conserved process involving the coordinated assembly and functioning of a multiprotein intraflagellar transport (IFT) complex. Among the various IFT proteins, intraflagellar transport 52 (IFT52) plays a crucial role in ciliary transport and is implicated in various ciliopathies. IFT52 is a core component of the IFT-B complex that facilitates movement of cargoes along the ciliary axoneme. Stable binding of the IFT-B1 and IFT-B2 subcomplexes by IFT52 in the IFT-B complex regulates recycling of ciliary components and maintenance of ciliary functions such as signal transduction and molecular movement. Mutations in the IFT52 gene can disrupt ciliary trafficking, resulting in dysfunctional cilia and affecting cellular processes in ciliopathies. Such ciliopathies caused by IFT52 mutations exhibit a wide range of clinical features, including skeletal developmental abnormalities, retinal degeneration, respiratory failure and neurological abnormalities in affected individuals. Therefore, IFT52 serves as a promising biomarker for the diagnosis of various ciliopathies, including short-rib thoracic dysplasia 16 with or without polydactyly. Here, we provide an overview of the IFT52-mediated molecular mechanisms underlying ciliary transport and describe the IFT52 mutations that cause different disorders associated with cilia dysfunction.
Topics: Humans; Biological Transport; Cilia; Ciliopathies; Flagella; Mutation; Protein Transport; Proteins; Signal Transduction
PubMed: 38272449
DOI: 10.1111/tra.12929 -
European Journal of Medical Genetics Apr 2024Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features,...
Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even rarer features such as hydrocephalus, facial paralysis, and cleft palate. We, hereby, report the case of the first patient with Lenz-Majewski syndrome (LMS) with molecular confirmation from Turkey. Although our patient had characteristic features described in the literature, she also had immunodeficiency, which has not been reported before. Although there is no established phenotype-genotype correlation, molecular mechanisms can be explained with the reporting of more patients.
Topics: Female; Humans; Intellectual Disability; Short Rib-Polydactyly Syndrome; Bone Diseases, Developmental; Otitis Media; Abnormalities, Multiple
PubMed: 38262577
DOI: 10.1016/j.ejmg.2024.104910 -
Nature Feb 2024Enhancers control the location and timing of gene expression and contain the majority of variants associated with disease. The ZRS is arguably the most well-studied...
Enhancers control the location and timing of gene expression and contain the majority of variants associated with disease. The ZRS is arguably the most well-studied vertebrate enhancer and mediates the expression of Shh in the developing limb. Thirty-one human single-nucleotide variants (SNVs) within the ZRS are associated with polydactyly. However, how this enhancer encodes tissue-specific activity, and the mechanisms by which SNVs alter the number of digits, are poorly understood. Here we show that the ETS sites within the ZRS are low affinity, and identify a functional ETS site, ETS-A, with extremely low affinity. Two human SNVs and a synthetic variant optimize the binding affinity of ETS-A subtly from 15% to around 25% relative to the strongest ETS binding sequence, and cause polydactyly with the same penetrance and severity. A greater increase in affinity results in phenotypes that are more penetrant and more severe. Affinity-optimizing SNVs in other ETS sites in the ZRS, as well as in ETS, interferon regulatory factor (IRF), HOX and activator protein 1 (AP-1) sites within a wide variety of enhancers, cause gain-of-function gene expression. The prevalence of binding sites with suboptimal affinity in enhancers creates a vulnerability in genomes whereby SNVs that optimize affinity, even slightly, can be pathogenic. Searching for affinity-optimizing SNVs in genomes could provide a mechanistic approach to identify causal variants that underlie enhanceropathies.
Topics: Humans; Enhancer Elements, Genetic; Extremities; Gain of Function Mutation; Homeodomain Proteins; Interferon Regulatory Factors; Organ Specificity; Penetrance; Phenotype; Polydactyly; Polymorphism, Single Nucleotide; Protein Binding; Proto-Oncogene Proteins c-ets; Transcription Factor AP-1
PubMed: 38233525
DOI: 10.1038/s41586-023-06922-8 -
Journal of Orthopaedic Surgery and... Jan 2024To investigate the functional and aesthetic results of a new modified Bilhaut-Cloquet procedure for the treatment of Wassel type III-IV thumb polydactyly.
BACKGROUND
To investigate the functional and aesthetic results of a new modified Bilhaut-Cloquet procedure for the treatment of Wassel type III-IV thumb polydactyly.
METHODS
Thirteen patients with Wassel type III-IV thumb polydactyly who visited the Department of Orthopedics of Hebei Provincial Children's Hospital from 2019 to 2022 were selected. The surgical procedure involved a modified Bilhaut-Cloquet surgery, where two-thirds of the distal part of the dominant finger was retained as the p body of the reconstructed thumb. The triangular bone block of the ablated distal thumb that did not contain the epiphysis and articular cartilage was sutured and fixed, and the neurovascular flap of the ablated distal thumb was used as an augmenting segment of the reconstructed thumb, with the nail bed and nail matrix exquisitely sutured. The evaluation performed according to the Japanese Society for Surgery of the Hand (JSSH) system.
RESULTS
All 13 children showed bone healing, no wound infection, nonunion, or deformity healing. None of the children showed a significant reduction in the active and passive mobility of the thumb postoperatively compared with preoperatively. Postoperative evaluation was performed based on the JSSH score, with a mean of 17.15 points (14-19 points), with 11 children rated as excellent and two as good. No severe nail ridges, nail gaps, or nail split deformities of the thumb were observed postoperatively. Postoperative metacarpophalangeal and interphalangeal joint movements were not reduced compared with preoperative movements. All parents were satisfied with the appearance and function of the reconstructed thumb.
CONCLUSION
The modified Bilhaut-Cloquet procedure designed in this study was satisfactory for Wassel type III-IV thumb polydactyly without affecting the stability of the interphalangeal joints and preserving joint mobility. The postoperative thumb has a comparable circumference and nail width and was cosmetically and functionally satisfactory, especially for the asymmetric two thumbs, which achieved favorable results.
Topics: Child; Humans; Infant; Polydactyly; Orthopedic Procedures; Thumb; Wound Healing
PubMed: 38229071
DOI: 10.1186/s13018-024-04553-x -
Taiwanese Journal of Obstetrics &... Jan 2024
Topics: Pregnancy; Female; Humans; Holoprosencephaly; Pregnancy Trimester, First; Trisomy 13 Syndrome; Polydactyly; Trisomy; Ultrasonography, Prenatal; Fingers; Toes
PubMed: 38216244
DOI: 10.1016/j.tjog.2023.10.007 -
Hand Surgery & Rehabilitation Apr 2024Thumb duplication is one of the most challenging pediatric reconstructive hand surgeries. Wassel types II and IV are the most frequent, but also the most complex... (Review)
Review
OBJECTIVES
Thumb duplication is one of the most challenging pediatric reconstructive hand surgeries. Wassel types II and IV are the most frequent, but also the most complex reconstructions as the duplication arises at the joint level. Ablation and reconstruction, the most widely used technique, aims at achieving a stable, well-aligned, mobile and esthetically acceptable thumb. The paucity of reliable surgical guidelines leads to high rates of suboptimal surgical outcomes. This review evaluated the various reconstruction techniques detailed in the literature and highlighted useful methods to prevent common secondary complications.
METHODS
A comprehensive PubMed and Embase literature search was made. Inclusion criteria were Wassel type II and/or IV, pediatric patients, and primary or secondary surgeries. Exclusion criteria were Bilhaut-Cloquet reconstruction and its modifications. Techniques were screened, collected and analyzed for the following secondary complications: instability, axial deformity, and contour deformity.
RESULTS
Thirty-two articles met the inclusion criteria and were reviewed. Postoperative instability was prevented by tightening the joint capsule by plication, advancement of the volar plate, or reconstruction of the collateral ligaments using a periosteal flap or the double-breasting technique. Axial deformity was prevented by arthroplasty, shaving a triangular portion of the metacarpal head, centralization of eccentric tendons, pulley reconstruction using flexor pollicis longus, or corrective osteotomies of the phalangeal or metacarpal bones using the wedge or oblique techniques. Limited range of motion was prevented by first webspace Z-plasty, and soft-tissue contouring was addressed by planned skin incisions and soft-tissue augmentation. Preoperative, perioperative and postoperative considerations, including splinting, imaging and immobilization, were also described.
CONCLUSION
Despite the ongoing advances and abundant knowledge in reconstructive strategies for thumb duplication, there are few studies that reviewed and analyzed the various reported options. This review provides physicians and trainees with guidance in surgical planning to prevent common secondary complications. Further research should focus on the development of standardized assessment tools, enabling reliable prospective comparative studies on thumb duplication reconstruction.
LEVEL OF EVIDENCE
IV.
Topics: Humans; Thumb; Postoperative Complications; Polydactyly; Plastic Surgery Procedures
PubMed: 38215882
DOI: 10.1016/j.hansur.2024.101642 -
African Journal of Disability 2023Bardet-Biedl syndrome (BBS) is a rare, systemic, hereditary disorder characterised by obesity, polydactyly, visual and auditory impairment, and cognitive disability....
BACKGROUND
Bardet-Biedl syndrome (BBS) is a rare, systemic, hereditary disorder characterised by obesity, polydactyly, visual and auditory impairment, and cognitive disability. Providing quality education in appropriate schools for children who present with such complex chronic conditions is challenging.
OBJECTIVES
This study explored the dimensions of psycho-educational support needs for a child with BBS in South Africa to contribute to the improvement of early detection and holistic interventions.
METHOD
A descriptive in-depth qualitative case study of Gezani, an adolescent Tsonga boy diagnosed with BBS, was undertaken. Semi-structured interviews were conducted with his parents and teachers to ascertain the boy's psycho-educational support needs. Medical reports provided information on the complexities and prognosis of the syndrome. Observations in the classroom corroborated the learner's symptoms and behaviours.
RESULTS
Thematic content analysis revealed the key areas of support needs. Gezani's cognitive disability required a modified, slow-paced curriculum. His visual impairment required mobility orientation training and learning Braille. His emotional needs were supported with psychotherapy to maintain a sense of well-being. Medical monitoring was recommended with interventions for walking and managing his diet and weight. Speech therapy supported his communication skills.
CONCLUSION
Learners with multiple disabilities require carefully planned, individualised psycho-educational support programmes addressing their unique needs and delays with targeted remedial interventions in appropriate special needs schools.
CONTRIBUTION
This study informs educators about BBS and provides multi-faceted, holistic support. The Department of Basic Education could bring special schools and national policies in tighter alignment for learners presenting with complex disabilities.
PubMed: 38204908
DOI: 10.4102/ajod.v12i0.1181