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Texas Heart Institute Journal Apr 2024Klippel-Feil syndrome, characterized by congenital fusion of any 2 or more cervical vertebrae, is a rare disorder in which skeletal and other organ system-related...
Klippel-Feil syndrome, characterized by congenital fusion of any 2 or more cervical vertebrae, is a rare disorder in which skeletal and other organ system-related abnormalities have been reported. This article reports a case of mitral valve regurgitation in a patient with Klippel-Feil syndrome and related thoracic deformity who underwent mitral valvuloplasty. Postoperatively, the mitral valve regurgitation disappeared, and there has been no recurrence for 3 years. This case highlights mitral valvuloplasty via median sternotomy as an excellent treatment for mitral valve regurgitation in a patient with thoracic deformity related to Klippel-Feil syndrome.
Topics: Adult; Humans; Male; Balloon Valvuloplasty; Klippel-Feil Syndrome; Mitral Valve; Mitral Valve Insufficiency; Sternotomy; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 38665003
DOI: 10.14503/THIJ-23-8282 -
Nature Apr 2024Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions. TS type 1 (TS1) is...
Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.
Topics: Animals; Female; Humans; Male; Mice; Alternative Splicing; Autistic Disorder; Calcium; Calcium Channels, L-Type; Cell Movement; Dendrites; Exons; Long QT Syndrome; Neurons; Oligonucleotides, Antisense; Organoids; Prosencephalon; Syndactyly; Interneurons
PubMed: 38658687
DOI: 10.1038/s41586-024-07310-6 -
Plastic and Reconstructive Surgery May 2024
Comparative Study
Topics: Humans; Craniosynostoses; Endoscopy; Craniotomy; Treatment Outcome; Infant
PubMed: 38657010
DOI: 10.1097/PRS.0000000000010780 -
Microsurgery May 2024Palmar finger or pulp defects require coverage with glabrous tissue to achieve a good match with the lost tissue. The management of multiple finger palmar or pulp...
BACKGROUND
Palmar finger or pulp defects require coverage with glabrous tissue to achieve a good match with the lost tissue. The management of multiple finger palmar or pulp defects is challenging because these defects may not always be suitable for local or pedicled flaps. In such situations, syndactylizing free or pedicled flaps can be used.
PATIENTS AND METHODS
We evaluated the results of free glabrous flaps syndactylizing across multiple finger defects. The two flaps used were the superficial branch of the radial artery (SUPBRA) flap and hypothenar free flap. Seven syndactylized glabrous free flaps were used to cover the defects in 16 fingers. The functional results and complaints were also assessed.
RESULTS
Mean flap size was 14.35 cm. Six flaps survived. Postoperative evaluation data were obtained for the 13 fingers. All the patients returned to their previous work. All patients had a diminished protective sensation of at least 4.31 according to the SWM test. The mean two-point discrimination score of the patients was 9.9 mm (7-14). One finger had a PIP joint flexion contracture of 30°, no donor-site complaints were observed.
CONCLUSION
The advantages of these flaps include single operation site, strong glabrous tissue coverage, low risk of flexion contracture, and adequate tissue size for large defects. Disadvantages include two-stage and complex microsurgical operations, prolonged treatment, and hospital stay.
Topics: Humans; Male; Finger Injuries; Adult; Female; Plastic Surgery Procedures; Free Tissue Flaps; Middle Aged; Young Adult; Syndactyly; Treatment Outcome; Retrospective Studies; Adolescent; Microsurgery; Graft Survival
PubMed: 38656753
DOI: 10.1002/micr.31161 -
Surgical and Radiologic Anatomy : SRA Jun 2024The use of 3D-printing in every field of medicine is expanding, notably as an educational tool. The aim of this study was to assess how visuospatial abilities (VSA) of...
PURPOSE
The use of 3D-printing in every field of medicine is expanding, notably as an educational tool. The aim of this study was to assess how visuospatial abilities (VSA) of students may impact learning helped with 3D-printed models.
METHODS
Participants were undergraduate medical school students during their clinical rotation in oral and maxillofacial surgery in two French Universities. Students were included prospectively and consecutively from September 2021 to June 2023. First, a lecture about craniosynostosis was performed with the help of 3D-printed models of craniosynostotic skulls. Then, a mental rotation test (MRT) followed by a multiple-choice questions (MCQs) form about craniosynostosis presentations were submitted to the students.
RESULTS
Forty undergraduate students were finally included. Median MRT score was 15 (10.75;21) and median score to the MCQs was 13 (11.75;14). There was a significantly weak correlation between the MRT-A score and the score to the MCQs (r = 0.364; p = 0.022). A simple linear regression was calculated to predict the result to the MCQs on MRT-A score [ (F(1,39) = 281.248; p < 0.0001), with a R2 of 0.878 ].
CONCLUSION
This study showed that VSA has an impact on the recognition of complex clinical presentations, i.e. skulls with craniosynostosis. The correlation found between VSA and complex 3D shape recognition after learning aided with 3D-printed model is emphasizing the importance of VSA when using innovative technologies. Thus, VSA training should be envisioned during the curriculum.
Topics: Humans; Printing, Three-Dimensional; Education, Medical, Undergraduate; Male; Female; Craniosynostoses; Prospective Studies; Students, Medical; Models, Anatomic; Young Adult; Surgery, Oral; Educational Measurement; France
PubMed: 38652251
DOI: 10.1007/s00276-024-03370-5 -
BMJ Case Reports Apr 2024Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals...
Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals aged 20-40 years but is rarely seen in children. We report a case of an infant with Rubenstein-Taybi syndrome presenting with nebulo-macular corneal opacity and congenital pterygium. On examination under anaesthesia, bilateral infero-nasal nebulo-macular corneal opacity (6 × 5 mm) with a whitish pink tissue originating from nasal bulbar conjunctiva was noticed. The probe test was negative for this tissue. To the best of our knowledge, only two other cases of congenital pterygium have been reported in the literature. The presence of this anomaly supports the hypothesis of genetic factors having a role in the development of pterygium.
Topics: Infant; Child; Humans; Pterygium; Rubinstein-Taybi Syndrome; Cornea; Corneal Opacity; Conjunctiva; Eye Abnormalities
PubMed: 38642933
DOI: 10.1136/bcr-2023-257962 -
Congenital Anomalies Jul 2024A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy...
A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole-exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia.
Topics: Humans; Female; Phenotype; Pregnancy; Adult; Ectodermal Dysplasia; Exome Sequencing; Ultrasonography, Prenatal; Mutation; Heterozygote; Bone and Bones; Craniosynostoses
PubMed: 38637985
DOI: 10.1111/cga.12569 -
Prenatal Diagnosis Apr 2024Here we trained an automatic phenotype assessment tool to recognize syndromic ears in two syndromes in fetuses-=CHARGE and Mandibulo-Facial Dysostosis Guion Almeida type...
OBJECTIVE
Here we trained an automatic phenotype assessment tool to recognize syndromic ears in two syndromes in fetuses-=CHARGE and Mandibulo-Facial Dysostosis Guion Almeida type (MFDGA)-versus controls.
METHOD
We trained an automatic model on all profile pictures of children diagnosed with genetically confirmed MFDGA and CHARGE syndromes, and a cohort of control patients, collected from 1981 to 2023 in Necker Hospital (Paris) with a visible external ear. The model consisted in extracting landmarks from photographs of external ears, in applying geometric morphometry methods, and in a classification step using machine learning. The approach was then tested on photographs of two groups of fetuses: controls and fetuses with CHARGE and MFDGA syndromes.
RESULTS
The training set contained a total of 1489 ear photographs from 526 children. The validation set contained a total of 51 ear photographs from 51 fetuses. The overall accuracy was 72.6% (58.3%-84.1%, p < 0.001), and 76.4%, 74.9%, and 86.2% respectively for CHARGE, control and MFDGA fetuses. The area under the curves were 86.8%, 87.5%, and 90.3% respectively for CHARGE, controls, and MFDGA fetuses.
CONCLUSION
We report the first automatic fetal ear phenotyping model, with satisfactory classification performances. Further validations are required before using this approach as a diagnostic tool.
PubMed: 38635411
DOI: 10.1002/pd.6577 -
American Journal of Medical Genetics.... Aug 2024Mucopolysaccharidosis type 10 is caused by biallelic variants in ARSK, which encodes for a lysosomal sulfatase. To date, seven patients with a mild phenotype resembling...
Mucopolysaccharidosis type 10 is caused by biallelic variants in ARSK, which encodes for a lysosomal sulfatase. To date, seven patients with a mild phenotype resembling spondyloepiphyseal dysplasia or multiple epiphyseal dysplasia have been described. In this report, we present two novel ARSK variants and report clinical and radiological findings of three patients. The patients' initial complaints were hip or knee pain and a waddling gait. All patients showed normal intelligence, normal hearing and eye examinations, and none had organomegaly. While typical dysostosis multiplex findings were not observed, mild platyspondyly with anterior beaking of some vertebral bodies, irregular vertebral endplates, wide ribs, inferior tapering of the ilea with a poorly developed acetabulum, irregularity of the central part of the femoral head, delayed ossification of the carpals were noted. Remarkably, all patients showed metaphyseal striation of the long bones, a crucial diagnostic clue to identify ARSK-related MPS type 10. Interestingly, vertebral involvement regressed during follow-up. On the other hand, hip dysplasia progressed in all patients. In conclusion, this study provides valuable long-term results on a recently discovered form of MPS.
Topics: Humans; Male; Female; Phenotype; Child; N-Acetylgalactosamine-4-Sulfatase; Adolescent; Mutation; Child, Preschool; Radiography; Osteochondrodysplasias
PubMed: 38634625
DOI: 10.1002/ajmg.a.63635 -
Gait & Posture Jun 2024The subtalar joint movement between the talus and calcaneus is restricted in patients with talocalcaneal coalition (TCC). When the motion of the subtalar joint is...
BACKGROUND
The subtalar joint movement between the talus and calcaneus is restricted in patients with talocalcaneal coalition (TCC). When the motion of the subtalar joint is restricted, shock absorption in the foot decreases, leading to pain during walking. Resection methods to maintain subtalar motion by removing abnormal unions have been proposed. The purpose of this study was to analyze the joint kinematics of patients who underwent TCC resection and to quantitatively evaluate the results of the surgery based on the measured kinematics.
METHODS
Joint kinematics of five patients with TCC were obtained using a biplane fluoroscopic imaging system and an intensity-based two-/three-dimensional registration method. The joint kinematics of the tibiotalar and subtalar joints and the tibiocalcaneal motion during the stance phase of walking were obtained. From the kinematics of the hindfoot joints, the inversion/eversion range of motion (ROM) of the patients before and after resection was statistically analyzed using the Wilcoxon signed-rank test to test whether TCC resection improved the ROM.
RESULTS
During the loading response period, the eversion ROM of the subtalar joint and tibiocalcaneal motion significantly increased postoperatively. In addition, a significant postoperative increase was observed in the subtalar and tibiocalcaneal inversion ROM during the pre-swing period.
SIGNIFICANCE
TCC resection surgery increased the ROM of the subtalar joint, which in turn contributed to the increase in tibiocalcaneal ROM. Increased subtalar and tibiocalcaneal ROM could result in increased shock attenuation and may be a contributing factor to pain relief during walking.
Topics: Humans; Biomechanical Phenomena; Male; Female; Subtalar Joint; Range of Motion, Articular; Calcaneus; Child; Adolescent; Fluoroscopy; Walking; Young Adult; Tarsal Coalition; Adult
PubMed: 38631260
DOI: 10.1016/j.gaitpost.2024.04.009