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Clinical Genetics Aug 2024RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras/MAPK pathways. Recently, a novel disease-gene association...
RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras/MAPK pathways. Recently, a novel disease-gene association was implicated in MAPK kinase kinase kinase 4 (MAP4K4), which regulates the upstream signals of the MAPK pathways. However, to our knowledge, only two studies have reported the genotype-phenotype relationships in the MAP4K4-related disorder. This study reports on a Korean boy harboring a novel de novo missense variant in MAP4K4 (NM_001242559:c.569G>T, p.Gly190Val), revealed by trio exome sequencing, and located in the hotspot of the protein kinase domain. The patient exhibited various clinical features, including craniofacial dysmorphism, language delay, congenital heart defects, genitourinary anomalies, and sagittal craniosynostosis. Our study expands the phenotypic association of the MAP4K4-related disorder to include syndromic craniosynostosis, thereby providing further insights into the role of the RAS/MAPK pathways in the development of premature fusion of calvarial sutures.
Topics: Humans; Mutation, Missense; Craniosynostoses; Male; Genetic Association Studies; Phenotype; Protein Serine-Threonine Kinases; Exome Sequencing; Heart Defects, Congenital; Syndrome; Genetic Predisposition to Disease
PubMed: 38679877
DOI: 10.1111/cge.14539 -
Journal of Medical Case Reports Apr 2024Sprengel's deformity is a congenital abnormality of the shoulder girdle. Because scapular retraction, such as the Green procedure, is usually performed during childhood...
BACKGROUND
Sprengel's deformity is a congenital abnormality of the shoulder girdle. Because scapular retraction, such as the Green procedure, is usually performed during childhood to improve esthetics and shoulder function, Sprengel's deformity is rarely found in older patients.
CASE PRESENTATION
We presented a unique case of a Japanese female cadaver with Sprengel's deformity at the age of 80 years. Anatomical dissection and radiological imaging revealed musculoskeletal anomalies associated with Sprengel's deformity, including Klippel-Feil syndrome, presence of an omovertebral bone, and absence of the trapezius muscle. In addition, bilateral cervical ribs were in contact with the brachial plexus. These anomalies may lead to numbness, pain, and limited range of motion of the neck and upper girdle with aging.
CONCLUSIONS
Because most adult patients with Sprengel's deformity experience neck pain and limited movement of the shoulder, the presented case is a rare case of neglected Sprengel's deformity in an 80-year-old cadaver.
Topics: Humans; Female; Aged, 80 and over; Cadaver; Scapula; Klippel-Feil Syndrome; Congenital Abnormalities; Brachial Plexus; Shoulder Joint
PubMed: 38678290
DOI: 10.1186/s13256-024-04528-w -
European Spine Journal : Official... Jun 2024Klippel-Feil syndrome (KF) is a rare disease defined as single or multi-level cervical vertebra fusion. KF could be accompanied by other spinal anomalies or isolated,...
PURPOSE
Klippel-Feil syndrome (KF) is a rare disease defined as single or multi-level cervical vertebra fusion. KF could be accompanied by other spinal anomalies or isolated, and in which case necessity of whole spine screening is not clearly known. KF is investigated in terms of prevalence, gender distribution, fusion types, and frequency of accompanying anomalies according to types of KF.
METHODS
Approval from our hospital's ethics committee was received for this single-center, retrospective study. Considering the exclusion criteria among the 40,901 cervical spine MRIs, 40,450 patients were included in the study. It was re-evaluated for KF, fusion level, classification, cervical scoliosis, and other musculoskeletal and spinal anomalies.
RESULTS
125 (0.309%) of 40,450 patients is diagnosed with KF, which is more common in women (P < 0.001). Single fused segment 106 (84.8%), multilevel fused segments 8 (6.4%), contiguous fused segments 11 (8.8%) are observed. Upper level KF is detected in 13 (10.4%) patients. The frequency of additional anomaly is significantly higher in upper level KF compared to other level fusions (P < 0.001, Chi-square t). The cervical scoliosis is diagnosed 34 (27%). In KF patients with scoliosis, the frequency of additional anomalies was significantly higher (P < 0.001, Chi-square t).
CONCLUSION
Klippel-Feil prevalence is 0.309%, it is frequently observed in women, and at C2-C3 level. Additional anomalies are especially associated with 'contiguous fused segments' and 'upper level' types. Klippel-Feil with scoliosis is an indicator of increased risk for associated anomalies, and examination of the whole spine is recommended.
Topics: Klippel-Feil Syndrome; Humans; Female; Male; Adult; Retrospective Studies; Middle Aged; Cervical Vertebrae; Adolescent; Child; Young Adult; Aged; Scoliosis; Prevalence; Child, Preschool; Magnetic Resonance Imaging
PubMed: 38676727
DOI: 10.1007/s00586-024-08281-y -
Genes Mar 2024The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated... (Review)
Review
The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the and genes. Significantly, the patient exhibited features associated with mutations, including distinctive traits such as cranial malformations. The gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the and genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management.
Topics: Humans; Male; Adolescent; Phenotype; Mutation; Peptide Termination Factors; Adaptor Protein Complex 4; Intellectual Disability; Exome Sequencing; Microcephaly; Craniosynostoses; Repressor Proteins
PubMed: 38674371
DOI: 10.3390/genes15040436 -
Medicina (Kaunas, Lithuania) Apr 2024: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the... (Review)
Review
: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the cervicomedullary junction, leading to neurological deficits. Severe cases require surgical intervention, but there is debate over the choice of approach. The anterior approach allows direct decompression but carries high complication rates, while the posterior approach provides indirect decompression and offers good stability with fewer complications. : A 15-year-old boy with severe myelopathy presented to our hospital with neck pain, bilateral upper limb muscle weakness, and hand numbness persisting for 4 years. Additionally, he experienced increased numbness and gait disturbance three months before his visit. On examination, he exhibited hyperreflexia in both upper and lower limbs, muscle weakness in the bilateral upper limbs (MMT 4), bilateral hypoesthesia below the elbow and in both legs, mild urinary and bowel incontinence, and a spastic gait. Radiographs revealed severe basilar invagination (BI). Preoperative images showed severe BI and that the spinal cord was severely compressed with odontoid process. : The patient underwent posterior surgery with the C-arm free technique. All screws including occipital screws were inserted into the adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year showed the following results: Manual muscle testing results and sensory function tests showed almost full recovery, with bilateral arm recovery (MMT 5) and smooth walking. The cervical Japanese Orthopedic Association score of the patient improved from 9/17 to 16/17. Postoperative images showed excellent spinal cord decompression, and no major or severe complications had occurred. : Basilar invagination alongside Klippel-Feil syndrome represents a relatively uncommon condition. Utilizing a posterior approach for treating reducible BI with a C-arm-free technique proved to be a safe method in addressing severe myelopathy. This novel navigation technique yields excellent outcomes for patients with BI.
Topics: Humans; Male; Adolescent; Klippel-Feil Syndrome; Decompression, Surgical; Platybasia; Treatment Outcome; Spinal Cord Compression
PubMed: 38674263
DOI: 10.3390/medicina60040616 -
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