-
Journal of Pediatric Neurosciences Jan 2014
PubMed: 24891917
DOI: 10.4103/1817-1745.131499 -
Orphanet Journal of Rare Diseases Jun 2006Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on... (Review)
Review
Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.
Topics: Acrocephalosyndactylia; Fingers; Genes, Dominant; Humans; Mutation; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 2; Toes
PubMed: 16740155
DOI: 10.1186/1750-1172-1-19 -
Heart Rhythm Jan 2010Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.
BACKGROUND
Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.
OBJECTIVE
This study sought to perform a retrospective analysis of BrS databases from 9 centers that have each genotyped >100 unrelated cases of suspected BrS.
METHODS
Mutational analysis of all 27 translated exons in SCN5A was performed. Mutation frequency, type, and localization were compared among cases and 1,300 ostensibly healthy volunteers including 649 white subjects and 651 nonwhite subjects (blacks, Asians, Hispanics, and others) that were genotyped previously.
RESULTS
A total of 2,111 unrelated patients (78% male, mean age 39 +/- 15 years) were referred for BrS genetic testing. Rare mutations/variants were more common among BrS cases than control subjects (438/2,111, 21% vs. 11/649, 1.7% white subjects and 31/651, 4.8% nonwhite subjects, respectively, P <10(-53)). The yield of BrS1 genetic testing ranged from 11% to 28% (P = .0017). Overall, 293 distinct mutations were identified in SCN5A: 193 missense, 32 nonsense, 38 frameshift, 21 splice-site, and 9 in-frame deletions/insertions. The 4 most frequent BrS1-associated mutations were E1784K (14x), F861WfsX90 (11x), D356N (8x), and G1408R (7x). Most mutations localized to the transmembrane-spanning regions.
CONCLUSION
This international consortium of BrS genetic testing centers has added 200 new BrS1-associated mutations to the public domain. Overall, 21% of BrS probands have mutations in SCN5A compared to the 2% to 5% background rate of rare variants reported in healthy control subjects. Additional studies drawing on the data presented here may help further distinguish pathogenic mutations from similarly rare but otherwise innocuous ones found in cases.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brugada Syndrome; Case-Control Studies; Child; Child, Preschool; Databases, Genetic; Death, Sudden, Cardiac; Exons; Female; Genetic Testing; Genotype; Global Health; Humans; Infant; Internationality; Male; Middle Aged; Multivariate Analysis; Muscle Proteins; Mutation, Missense; NAV1.5 Voltage-Gated Sodium Channel; Retrospective Studies; Risk Factors; Sodium Channels; Young Adult
PubMed: 20129283
DOI: 10.1016/j.hrthm.2009.09.069 -
Cureus Dec 2023Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture,... (Review)
Review
Craniosynostosis is a fetal skull condition that occurs when one or multiple sutures merge prematurely. This leads to limited growth perpendicular to the fused suture, which results in compensatory growth of cranial bones parallel to it. Syndromic craniosynostosis ensues when the cranial deformity is accompanied by respiratory, neurological, cardiac, musculoskeletal, and audio-visual abnormalities. The most common syndromes are Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes and craniofrontonasal syndrome. Each of these syndromes has distinct genetic mutations that contribute to their development. Mutations in genes such as FGFR, TWIST, and EFNB1 have been identified as playing a role in the development of these syndromes. Familiarity with the genetic basis of each syndrome is not only essential for identifying them but also advantageous for current pharmacological investigations. Surgical treatment is often necessary for syndromic craniosynostosis to correct the cranial deformities. Advances have been made in surgical techniques for each specific syndrome, but further research is needed to develop personalized approaches that address the unique symptoms and complications of individual patients, particularly those related to neurological and respiratory issues. This group of syndromes included in cranial synostosis presents significant educational and clinical interest due to the wide range of symptoms and the variable course of the disease, especially in the last decades when crucial advances in diagnosis and treatment have been achieved, altering the prognosis as well as the quality of life of these patients. In summary, this article provides a comprehensive overview of syndromic craniosynostosis, including the genetic mutations associated with each syndrome and the surgical treatment options available.
PubMed: 38222144
DOI: 10.7759/cureus.50448 -
Journal of Korean Neurosurgical Society May 2016Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various... (Review)
Review
Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.
PubMed: 27226847
DOI: 10.3340/jkns.2016.59.3.187 -
EMBO Molecular Medicine Nov 2018Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires complex...
Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires complex procedures impeding the broad supply chain. Here, we provide evidence that human CD19-CAR T cells can be generated directly using the lentiviral vector CD8-LV specifically targeting human CD8 cells. Administration into mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells led to CAR expression solely in CD8 T cells and efficacious elimination of CD19 B cells. Further, upon injection of CD8-LV into mice transplanted with human CD34 cells, induction of CAR T cells and CD19 B-cell depletion was observed in 7 out of 10 treated animals. Notably, three mice showed elevated levels of human cytokines in plasma. Tissue-invading CAR T cells and complete elimination of the B-lymphocyte-rich zones in spleen were indicative of a cytokine release syndrome. Our data demonstrate the feasibility of reprogramming of human CD8 CAR T cells active against CD19 cells, yet with similar adverse effects currently notorious in the clinical practice.
Topics: Animals; Antigens, CD19; B-Lymphocytes; Cytokines; Graft vs Host Disease; HEK293 Cells; Humans; Leukocytes, Mononuclear; Lymphocyte Depletion; Mice; Receptors, Chimeric Antigen; Syndrome; T-Lymphocytes
PubMed: 30224381
DOI: 10.15252/emmm.201809158 -
Clinical Oral Investigations Mar 2022To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial...
OBJECTIVES
To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group.
MATERIAL AND METHODS
We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children.
RESULTS
Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: β = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: β = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: β = -1.70, p = 0.015; and PC1: p < 0.033).
CONCLUSIONS
In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls.
CLINICAL RELEVANCE
The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.
Topics: Acrocephalosyndactylia; Adolescent; Basic Helix-Loop-Helix Transcription Factors; Cephalometry; Child; Child, Preschool; Craniosynostoses; Humans; Syndrome
PubMed: 34904178
DOI: 10.1007/s00784-021-04275-y -
In Vivo (Athens, Greece) 2023Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%),... (Review)
Review
Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%), craniosynostosis is presented as sporadic anomaly (non-syndromic craniosynostosis), while in other cases (15%) as part of syndromes (syndromic craniosynostosis). Patients with syndromic disorder usually have more severe symptoms compared to those with single suture synostosis. Most common syndromes of craniosynostosis include Pfeiffer, Apert, Crouzon, Jackson-Weiss, Muenke and Boston type MSX2-related syndrome. The main gene mutations in craniosynostosis involve FGFR1, FGFR2, FGFR3, TWIST1 and MSX2, which encode key factors influencing cranial bone morphogenesis. The main therapeutic approaches are surgical as discussed in this review, and the type of therapy depends on the graveness of the incident.
Topics: Humans; Craniosynostoses; Skull; Mutation; Syndrome
PubMed: 36593018
DOI: 10.21873/invivo.13052 -
Ugeskrift For Laeger Dec 2023In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still... (Review)
Review
In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing.
Topics: Humans; Immunotherapy; Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms
PubMed: 38105736
DOI: No ID Found