-
Molecular Genetics and Metabolism... Dec 2023Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the gene, leading to alpha-L-fucosidase deficiency; it is inherited as an...
Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affected patients have slow neurologic deterioration. Many patients die young and the long-term clinical outcomes in adult patients are poorly documented. Here, we report the long-term follow up of two Caucasian siblings, a 31-year-old man and 25-year-old woman. We describe the clinical, biochemical, radiological and genetic findings in two siblings affected by Fucosidosis and the differences between them after 19-years follow up. The dermatological features of the younger sibling have been reported previously by Bharati et al. (2007). Both patients have typical features of Fucosidosis, such as learning difficulties, ataxia, and angiokeratomas with differing severity. Case 1 presents severe ataxia with greater limitation of mobility, multiple dysostoses, angiokeratomas on his limbs, retinal vein enlargement and increased tortuosity in the eye and gastrointestinal symptoms. Biochemical analysis demonstrated a deficiency of alpha-fucosidase in leucocytes. Case 2 has a greater number of angiokeratomas and has suffered three psychotic episodes. The diagnosis of Fucosidosis was confirmed in cultured skin fibroblast at the age of 12 years. Molecular analysis of the gene showed a heterozygous mutation c.998G > A p.(Gly333Asp), with a pathogenic exon 4 deletion in the other allele in both patients. Conclusion. Fucosidosis presents a wide clinical heterogeneity and intrafamilial variability of symptoms. Psychosis and gastrointestinal symptoms have not been reported previously in Fucosidosis.
PubMed: 38053939
DOI: 10.1016/j.ymgmr.2023.101009 -
Scientific Reports Dec 2023Spring-assisted posterior vault expansion has been adopted at the London Great Ormond Street Hospital for Children to treat raised intracranial pressure in patients...
Spring-assisted posterior vault expansion has been adopted at the London Great Ormond Street Hospital for Children to treat raised intracranial pressure in patients affected by syndromic craniosynostosis, a congenital calvarial anomaly causing the premature fusion of skull sutures. This procedure involves elastic distractors used to dynamically reshape the skull and increase the intracranial volume (ICV). In this study, we developed and validated a patient-specific model able to predict the ICV increase and carried out a parametric study to investigate the effect of surgical parameters on that final volume. Pre- and post-operative computed tomography data relative to 18 patients were processed to extract simplified patient-specific skull shape, replicate surgical cuts, and simulate spring expansion. A parametric study was performed to quantify each parameter's impact on the surgical outcome: for each patient, the osteotomy location was varied in a pre-defined range; local sensitivity of the predicted ICV to each parameter was analysed and compared. Results showed that the finite element model performed well in terms of post-operative ICV prediction and allowed for parametric optimization of surgical cuts. The study indicates how to optimize the ICV increase according to the type of procedure and provides indication on the most robust surgical strategy.
Topics: Child; Humans; Infant; Skull; Craniosynostoses; Cranial Sutures; Tomography, X-Ray Computed; Osteotomy
PubMed: 38049445
DOI: 10.1038/s41598-023-48143-z -
PloS One 2023Sagittal synostosis is a condition caused by the fused sagittal suture and results in a narrowed skull in infants. Spring-assisted cranioplasty is a correction technique...
Sagittal synostosis is a condition caused by the fused sagittal suture and results in a narrowed skull in infants. Spring-assisted cranioplasty is a correction technique used to expand skulls with sagittal craniosynostosis by placing compressed springs on the skull before six months of age. Proposed methods for surgical planning in spring-assisted sagittal craniosynostosis correction provide information only about the skull anatomy or require iterative finite element simulations. Therefore, the selection of surgical parameters such as spring dimensions and osteotomy sizes may remain unclear and spring-assisted cranioplasty may yield sub-optimal surgical results. The aim of this study is to develop the architectural structure of an automated tool to predict post-operative surgical outcomes in sagittal craniosynostosis correction with spring-assisted cranioplasty using machine learning and finite element analyses. Six different machine learning algorithms were tested using a finite element model which simulated a combination of various mechanical and geometric properties of the calvarium, osteotomy sizes, spring characteristics, and spring implantation positions. Also, a statistical shape model representing an average sagittal craniosynostosis calvarium in 5-month-old patients was used to assess the machine learning algorithms. XGBoost algorithm predicted post-operative cephalic index in spring-assisted sagittal craniosynostosis correction with high accuracy. Finite element simulations confirmed the prediction of the XGBoost algorithm. The presented architectural structure can be used to develop a tool to predict the post-operative cephalic index in spring-assisted cranioplasty in patients with sagittal craniosynostosis can be used to automate surgical planning and improve post-operative surgical outcomes in spring-assisted cranioplasty.
Topics: Infant; Humans; Finite Element Analysis; Craniotomy; Plastic Surgery Procedures; Craniosynostoses; Skull; Retrospective Studies
PubMed: 38015830
DOI: 10.1371/journal.pone.0294879 -
European Journal of Paediatric Dentistry Dec 2023Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2...
Mandibulofacial dysostosis Guion-Almeida Type (MFDGA; OMIM#610536) is a rare autosomal dominant genetic disorder caused by heterozygous pathogenic variants in the EFTUD2 gene. Mandibulofacial dysostoses are characterised by the core triad malar hypoplasia, maxillary hypoplasia and dysplastic ears, all derived by the impaired development of the first and second branchial arches. Differential diagnosis is often challenging. The early genetic diagnosis is extremely useful, not only for the correct management of cranial malformations, but also for the early diagnosis and treatment of the comorbidities associated to the disease, which greatly benefit from early treatment.
Topics: Humans; Branchial Region; Mandibulofacial Dysostosis; Diagnosis, Differential; Zygoma; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 38015115
DOI: 10.23804/ejpd.2023.24.04.03 -
Molecular Genetics & Genomic Medicine Jan 2024Cenani-Lenzsyndactyly syndrome (CLSS; OMIM 212780) is a rare autosomal recessive acral deformity, which is mainly manifested in the fusion of fingers or toes,... (Review)
Review
BACKGROUND
Cenani-Lenzsyndactyly syndrome (CLSS; OMIM 212780) is a rare autosomal recessive acral deformity, which is mainly manifested in the fusion of fingers or toes, disordered phalangeal structure, shortening or fusion of the radius and ulna, and renal hypoplasia.
CASE PRESENTATION
Our report described an individual with mild phenotypes from China. His parents were not consanguineous. The affected individual was non-dysmorphic. Standard X-ray showed that the both hands have only four metacarpal bones. The distal end of the first metacarpal bone on the right was relatively slender, and the distal phalanx was absent. Multiple phalanges and some soft tissues of both hands were fused. Exome sequencing revealed a novel biallelic c.282C⟩Avariant in low-density lipoprotein receptor-related protein 4 (LRP4; OMIM604270; NM_002334.4) causing p. (Asn94Lys) change in the encoded protein. This variant is predicted to be potentially pathogenic, affecting protein structure and function.
CONCLUSION
We report a novel missense variant present in homozygosity in LRP4 to broaden the pathogenic spectrum of LRP4 in syndactyly, and exome sequencing technology is a powerful tool for genetic analysis in prenatal diagnosis and medical research, as a preferred method for the diagnosis of syndactyly and related phenotypes.
Topics: Humans; Mutation; LDL-Receptor Related Proteins; Syndactyly; Mutation, Missense
PubMed: 38013226
DOI: 10.1002/mgg3.2319 -
Scientific Reports Nov 2023We present the first data-driven pediatric model that explains cranial sutural growth in the pediatric population. We segmented the cranial bones in the neurocranium...
We present the first data-driven pediatric model that explains cranial sutural growth in the pediatric population. We segmented the cranial bones in the neurocranium from the cross-sectional CT images of 2068 normative subjects (age 0-10 years), and we used a 2D manifold-based cranial representation to establish local anatomical correspondences between subjects guided by the location of the cranial sutures. We designed a diffeomorphic spatiotemporal model of cranial bone development as a function of local sutural growth rates, and we inferred its parameters statistically from our cross-sectional dataset. We used the constructed model to predict growth for 51 independent normative patients who had longitudinal images. Moreover, we used our model to simulate the phenotypes of single suture craniosynostosis, which we compared to the observations from 212 patients. We also evaluated the accuracy predicting personalized cranial growth for 10 patients with craniosynostosis who had pre-surgical longitudinal images. Unlike existing statistical and simulation methods, our model was inferred from real image observations, explains cranial bone expansion and displacement as a consequence of sutural growth and it can simulate craniosynostosis. This pediatric cranial suture growth model constitutes a necessary tool to study abnormal development in the presence of cranial suture pathology.
Topics: Humans; Child; Infant, Newborn; Infant; Child, Preschool; Cranial Sutures; Craniosynostoses; Skull; Palliative Care
PubMed: 37996454
DOI: 10.1038/s41598-023-47622-7 -
Clinical Genetics Mar 2024We report the case of a 12-year-old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing...
We report the case of a 12-year-old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing loss. The CATSHL (CAmptodactyly - Tall stature - Scoliosis - Hearing Loss syndrome) syndrome was suspected, and molecular analysis revealed a hitherto unreported, monoallelic variant c.1861C>T (p.Arg621Cys) in FGFR3. This variant affects the same residue, but is different than, the variant p.Arg621His reported in the two families with dominant CATSHL described so far. Interestingly, peg-shaped incisors were observed in the proband, a feature never reported in CATSHL but typical of another FGFR3-related condition, LADD (Lacrimo - Auricolo - Dento - Digital) syndrome. The FGFR3 p.Arg621Cys variant seems to be a newly identified cause of CATSHL syndrome with some phenotypic overlap with the LADD syndrome.
Topics: Female; Humans; Child; Scoliosis; Hearing Loss; Bone Diseases, Developmental; Deafness; Syndrome; Limb Deformities, Congenital; Hand Deformities, Congenital; Lacrimal Apparatus Diseases; Tooth Abnormalities; Syndactyly; Abnormalities, Multiple
PubMed: 37990933
DOI: 10.1111/cge.14455 -
The Journal of Hand Surgery, European... May 2024This study evaluated how Apert hand syndactyly presentations and reconstructive techniques influence reconstruction outcomes. All cases at a major paediatric hospital...
UNLABELLED
This study evaluated how Apert hand syndactyly presentations and reconstructive techniques influence reconstruction outcomes. All cases at a major paediatric hospital between 2007 and 2022 were analysed, including 98 web space reconstructions in 17 patients. Overall, 62% of hands developed complications and 15% required revision surgery. Upton hand type was significantly associated with postoperative complication incidence, specifically including range-of-motion deficits, flexion contracture, web creep and revision surgery. More severe syndactylies may benefit from additional measures to reduce complications. Rectangular commissural flaps showed 1.9 times greater complication risk than interdigitating triangular flaps, including 11.2 times greater risk of web creep. Zigzag volar finger flaps showed 1.8 times greater complication risk than straight-line incisions, including 3.8 times greater risk of web creep. Our study showed that interdigitating triangular commissural flaps and straight-line volar finger incisions are preferable to rectangular commissural and zigzag finger flaps in most cases of Apert hand syndactyly to minimize complications.
LEVEL OF EVIDENCE
III.
Topics: Humans; Male; Female; Postoperative Complications; Surgical Flaps; Risk Factors; Infant; Plastic Surgery Procedures; Acrocephalosyndactylia; Child, Preschool; Reoperation; Retrospective Studies; Syndactyly; Child; Range of Motion, Articular
PubMed: 37987676
DOI: 10.1177/17531934231213516 -
Scientific Reports Nov 2023The early and accurate diagnosis of brachycephalic obstructive airway syndrome (BOAS) in dogs is pivotal for effective treatment and enhanced canine well-being. Owners...
The early and accurate diagnosis of brachycephalic obstructive airway syndrome (BOAS) in dogs is pivotal for effective treatment and enhanced canine well-being. Owners often do underestimate the severity of BOAS in their dogs. In addition, traditional diagnostic methods, which include pharyngolaryngeal auscultation, are often compromised by subjectivity, are time-intensive and depend on the veterinary surgeon's experience. Hence, new fast, reliable assessment methods for BOAS are required. The aim of the current study was to use machine learning techniques to bridge this scientific gap. In this study, machine learning models were employed to objectively analyze 366 audio samples from 69 Pugs and 79 other brachycephalic breeds, recorded with an electronic stethoscope during a 15-min standardized exercise test. In classifying the BOAS test results as to whether the dog is affected or not, our models achieved a peak accuracy of 0.85, using subsets from the Pugs dataset. For predictions of the BOAS results from recordings at rest in Pugs and various brachycephalic breeds, accuracies of 0.68 and 0.65 were observed, respectively. Notably, the detection of laryngeal sounds achieved an F1 score of 0.80. These results highlight the potential of machine learning models to significantly streamline the examination process, offering a more objective assessment than traditional methods. This research indicates a turning point towards a data-driven, objective, and efficient approach in canine health assessment, fostering standardized and objective BOAS diagnostics.
Topics: Dogs; Animals; Respiratory Sounds; Dog Diseases; Airway Obstruction; Larynx; Treatment Outcome; Craniosynostoses; Syndrome
PubMed: 37985864
DOI: 10.1038/s41598-023-47308-0 -
Journal of the American Academy of... May 2024
Topics: Humans; Epidermolysis Bullosa Dystrophica; Syndactyly; Contracture; Epidermolysis Bullosa
PubMed: 37977295
DOI: 10.1016/j.jaad.2023.11.012