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American Journal of Audiology Jun 2014There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and... (Review)
Review
PURPOSE
There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their ligands, fibroblast growth factors (FGFs), have revealed clues to the precise contribution of aberrant FGFR signaling to inner ear morphogenesis and the hearing loss encountered in craniosynostoses. The purpose of this article is to review basic studies of FGFRs with emphasis on their function and expression in the inner ear and surrounding structures.
METHOD
A Medline search was performed to find basic science articles regarding FGFR, their ligands, and their expression and relevant mouse models. Additional items searched included clinical descriptions and studies of individuals with FGFR-related craniosynostosis syndromes.
RESULTS
The FGF signaling pathway is essential for the morphogensis and proper function of the inner ear and auditory sensory epithelium.
CONCLUSION
The variable auditory phenotypes seen in individuals with Muenke syndrome may have a genetic basis, likely due to multiple interacting factors in the genetic environment or modifying factors. Further analysis and studies of mouse models of Muenke syndrome, in particular, may provide clues to the specific effects of the defining mutation in FGFR3 in the inner ear not only at birth but also into adulthood. In particular, investigations into these models may give insight into the variable expression and incomplete penetrance of this phenotype.
Topics: Animals; Child; Craniosynostoses; Deafness; Disease Models, Animal; Genetic Therapy; Hearing Loss; Humans; Mice; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor; Signal Transduction; Syndrome
PubMed: 24686979
DOI: 10.1044/2014_AJA-13-0036 -
Revista Brasileira de Terapia Intensiva 2022To determine the incidence of postintensive care syndrome in a cohort of critically ill patients admitted to the intensive care unit and to identify risk factors related... (Observational Study)
Observational Study
OBJECTIVE
To determine the incidence of postintensive care syndrome in a cohort of critically ill patients admitted to the intensive care unit and to identify risk factors related to its development in the physical, cognitive and mental health areas.
METHODS
This was a prospective observational cohort study developed in the intensive care unit of a university hospital. Patients with intensive care unit stays equal to or longer than one week and the need for mechanical ventilation for more than 3 days, shock or delirium were included in the study. Demographic variables, reasons for admission, diagnoses, sedation, type of mechanical ventilation used, complications and length of stay were recorded. A univariate analysis was performed to identify risk factors related to postintensive care syndrome. The scales used for the assessment of the different spheres were Barthel, Pfeiffer, Hospital Anxiety and Depression Scale and Impact of Event Scale-6. The main variables of interest were postintensive care syndrome incidence overall and by domains. Risk factors were examined in each of the health domains (physical, cognitive and mental health).
RESULTS
Eighty-seven patients were included. The mean Acute Physiology and Chronic Health Evaluation II score was 16.5. The mean number of intensive care unit days was 17. The incidence of global postintensive care syndrome was 56.3% (n = 49, 95%CI 45.8 - 66.2%). The incidence of postintensive care syndrome in each of the spheres was 32.1% (physical), 11.5% (cognitive), and 36.6% (mental health).
CONCLUSIONS
The incidence of postintensive care syndrome is 56.3%. The mental health sphere is the most frequently involved. The risk factors are different depending on the area considered.
Topics: Humans; Critical Illness; Incidence; Prospective Studies; Intensive Care Units; Respiration, Artificial; Cohort Studies; Risk Factors
PubMed: 36351069
DOI: 10.5935/0103-507X.20220224-pt -
Dental and Medical Problems 2018Saethre-Chotzen syndrome (SCS) belongs to a group of rare congenital disorders connected with craniosynostosis and syndactyly. The purpose of this paper is to provide a... (Review)
Review
Saethre-Chotzen syndrome (SCS) belongs to a group of rare congenital disorders connected with craniosynostosis and syndactyly. The purpose of this paper is to provide a review of the literature, to collect all reported symptoms and to describe the case of an 11-year-old female with SCS. The electronic databases PubMed and Scopus were searched to gain all symptoms of SCS described in the literature. The most common features of SCS described in the literature are synostosis of the coronal suture, syndactyly, facial asymmetry, low hairline, prominent ear crus, prominent nasal bridge, eyelid ptosis, and ocular hypertelorism. Less common symptoms include hearing loss, renal abnormalities and cardiac defects. Intraoral manifestations of SCS include maxillary hypoplasia, mandibular prognathism and high arched palate. Moreover, in some patients mental disability is observed, which may be connected with the size of the deletion in the Twist gene. There are no pathognomonic symptoms of SCS, which would indicate a diagnostic problem. Our patient displayed small dysmorphic changes within the skull and limbs and proper intellectual development. On the basis of an intraoral, extraoral examination and X-rays, she was diagnosed with relative mandibular prognathism. Currently, she is treated with a removable appliance. This report emphasizes a considerable variability of symptoms in SCS and highlights the most common features.
Topics: Acrocephalosyndactylia; Cephalometry; Child; Female; Humans; Orthodontic Appliances, Removable; Phenotype; Prognathism; Radiography, Panoramic
PubMed: 30152628
DOI: 10.17219/dmp/91050 -
Disease Models & Mechanisms May 2019One diagnostic feature of craniosynostosis syndromes is mandibular dysgenesis. Using three mouse models of Apert, Crouzon and Pfeiffer craniosynostosis syndromes, we...
One diagnostic feature of craniosynostosis syndromes is mandibular dysgenesis. Using three mouse models of Apert, Crouzon and Pfeiffer craniosynostosis syndromes, we investigated how embryonic development of the mandible is affected by fibroblast growth factor receptor 2 () mutations. Quantitative analysis of skeletal form at birth revealed differences in mandibular morphology between mice carrying mutations and their littermates that do not carry the mutations. Murine embryos with the mutations associated with Apert syndrome in humans ( and ) showed an increase in the size of the osteogenic anlagen and Meckel's cartilage (MC). Changes in the microarchitecture and mineralization of the developing mandible were visualized using histological staining. The mechanism for mandibular dysgenesis in the Apert mouse resulting in the most severe phenotypic effects was further analyzed in detail and found to occur to a lesser degree in the other craniosynostosis mouse models. Laser capture microdissection and RNA-seq analysis revealed transcriptomic changes in mandibular bone at embryonic day 16.5 (E16.5), highlighting increased expression of genes related to osteoclast differentiation and dysregulated genes active in bone mineralization. Increased osteoclastic activity was corroborated by TRAP assay and hybridization of and Upregulated expression of and was validated in the mandible of embryos, and found to result in elevated inorganic pyrophosphate concentration. Increased proliferation of osteoblasts in the mandible and chondrocytes forming MC was identified in embryos at E12.5. These findings provide evidence that FGFR2 gain-of-function mutations differentially affect cartilage formation and intramembranous ossification of dermal bone, contributing to mandibular dysmorphogenesis in craniosynostosis syndromes.This article has an associated First Person interview with the joint first authors of the paper.
Topics: Animals; Cell Proliferation; Chondrocytes; Craniosynostoses; Diphosphates; Disease Models, Animal; Embryo, Mammalian; Mandible; Mice; Models, Biological; Osteoblasts; Osteogenesis; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 31064775
DOI: 10.1242/dmm.038513 -
Pfeiffer-like syndrome with holoprosencephaly: a newborn with maternal smoking and alcohol exposure.Pediatrics and Neonatology Oct 2009We report the case of a female infant with Pfeiffer-like syndrome and holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and halluces, and...
We report the case of a female infant with Pfeiffer-like syndrome and holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and halluces, and variable accompanying anomalies compatible with Pfeiffer syndrome. She also displayed microcephaly, short palpebral fissures, and a smooth philtrum, which are clinical signs consistent with fetal alcohol syndrome. She suffered from multiple congenital anomalies and died at 41 days of age. Cardio-pulmonary failure, brain abnormalities, prematurity, and multiple complications contributed to her death. The patient displayed normal chromosomal numbers and type. DNA analysis did not reveal fibrobtast growth factor receptor (FGFR) genes FGFR1, FGFR2, FGFR3 or TWIST gene mutations. We review the previous reports of Pfeiffer syndrome and holoprosencephaly and describe our infant patient with Pfeiffer-like syndrome, holoprosencephaly, and heavy in utero maternal alcohol and smoking exposures.
Topics: Acrocephalosyndactylia; Alcohol Drinking; Female; Holoprosencephaly; Humans; Infant, Newborn; Receptors, Fibroblast Growth Factor; Smoking
PubMed: 19856868
DOI: 10.1016/S1875-9572(09)60069-3 -
American Journal of Human Genetics Mar 2000Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2...
Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequenced and were assayed by heteroduplex analysis, to identify polymorphisms. Two polymorphisms (1333TA/TATA and 2710 C/T) were found and were used with two previously described polymorphisms, to screen a total of 41 families. Twenty-two of these families were shown to be informative (11 for Crouzon syndrome and 11 for Pfeiffer syndrome). Eleven different mutations in the 22 families were detected by either restriction digest or allele-specific oligonucleotide hybridization of ARMS PCR products. We molecularly proved the origin of these different mutations to be paternal for all informative cases analyzed (P=2. 4x10-7; 95% confidence limits 87%-100%). Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals (34. 50+/-7.65 years vs. 30.45+/-1.28 years, P<.01). Our data on advanced paternal age corroborates and extends previous clinical evidence based on statistical analyses as well as additional reports of advanced paternal age associated with paternal origin of three sporadic mutations causing Apert syndrome (FGFR2) and achondroplasia (FGFR3). Our results suggest that older men either have accumulated or are more susceptible to a variety of germline mutations.
Topics: Acrocephalosyndactylia; Adult; Aging; Alleles; Craniofacial Dysostosis; Exons; Fathers; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Germ-Line Mutation; Heteroduplex Analysis; Humans; Introns; Male; Middle Aged; Molecular Sequence Data; Mothers; Pedigree; Polymorphism, Genetic; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor
PubMed: 10712195
DOI: 10.1086/302831 -
Deutsches Arzteblatt International Nov 2013As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD--impaired social interaction and communication,... (Review)
Review
BACKGROUND
As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD--impaired social interaction and communication, bizarre interests--are now commonly recognized as being typical of autism, not only in children, but in adults as well. More often than before, general practitioners, neurologists, and psychiatrists find themselves being asked whether a patient is suffering from previously unrecognized Asperger syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic evaluation of AS in adulthood.
METHOD
We selectively searched the Medline database for pertinent literature, paying special attention to diagnostic manuals and to the guideline of the United Kingdom's National Institute for Health and Care Excellence (NICE).
RESULTS
Centrally important aspects of the diagnosis of AS include an assessment of the patient's ability to assume the emotional perspectives of others, non-verbal modes of expression, repetitive behavior patterns, and childhood social behavioral history. The autism quotient (AQ) is now established as a simple but nonspecific screening test. Up to 70% of all affected adults have comorbid disturbances, most often depression and anxiety disorders. The differential diagnosis includes personality disorders, anxiety disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The diagnostic assessment should proceed in stepwise fashion, starting from simple screening in primary care and then moving on to evaluation of the suspected diagnosis by a mental health care specialist, followed by extensive further investigation in an outpatient clinic specifically devoted to patients with autism spectrum disorders.
CONCLUSION
The diagnostic assessment of autism in adults requires knowledge of the core and accompanying manifestations of autism and of their differential diagnoses. More research is needed for the development of further screening tests and the precise determination of diagnosis rates, differential diagnoses, nd comorbidities.
Topics: Asperger Syndrome; Diagnosis, Differential; Humans; Medical History Taking; Neuropsychological Tests; Psychometrics
PubMed: 24290364
DOI: 10.3238/arztebl.2013.0755 -
Veterinary Sciences Feb 2022Infection of pig farms with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) causes substantial economic losses globally....
First Study to Describe the Prevalence of Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus Type 2 among the Farmed Pig Population in the Hong Kong Special Administrative Region.
Infection of pig farms with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) causes substantial economic losses globally. However, little epidemiological data of PRRSV and PCV2 in the Hong Kong Special Administrative Region (HKSAR) were available. This pilot study aimed to provide baseline information of the prevalences of PPRSV and PCV2 in the HKSAR. A complex survey was conducted from 3 February 2020 to 11 March 2021 on 29 of the 40 pig farms in the HKSAR, with five pigs each from seven age groups (representing key production stages) tested using a real-time PCR. Evidence of presence of PRRSV European strain (PRRSV-1), PRRSV North American strain (PRRSV-2) and PCV2 was confirmed on 48%, 86% and 79% of farms, with overall prevalences of 7.6% (95% CI: 4.8-10.3%), 12.2% (95% CI: 9.6-14.7%) and 20.3% (95% CI: 14.3-26.2%) in the HKSAR pig population based on pooling results from all pigs across all farms. PRRSV-1 and PRRSV-2 were more prevalent in younger pigs, with the highest prevalences of 32.1% (95% CI: 20.8-45.0%) and 51.5% (95% CI: 38.9-64.0%) for 8-week-old pigs. In contrast, the distribution of PCV2 prevalence across age groups appeared to be more symmetrical, with higher prevalences reported in pigs from 12 weeks old to 24 weeks old but lower prevalences in younger pigs and sows. The results of this study demonstrate that PRRSV-1, PRRSV-2 and PCV2 are widely spread across pig farms in the HKSAR, which indicates that the current farm management and control protocols should be improved. We recommend the implementation of on-farm intervention strategies combined with ongoing surveillance to reduce these viruses, and their consequences, in the HKSAR pig population.
PubMed: 35202333
DOI: 10.3390/vetsci9020080 -
Pediatric Nephrology (Berlin, Germany) Jun 2016Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many... (Review)
Review
Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.
Topics: Acanthosis Nigricans; Acrocephalosyndactylia; Animals; Antley-Bixler Syndrome Phenotype; Apoptosis; Craniosynostoses; Ear; Fibroblast Growth Factors; Gene Knockout Techniques; Humans; Kidney; Mice; Models, Animal; Mutation; Organogenesis; Receptors, Fibroblast Growth Factor; Scalp Dermatoses; Signal Transduction; Skin Abnormalities; T-Box Domain Proteins; Ureter; Urinary Bladder; Wolffian Ducts
PubMed: 26293980
DOI: 10.1007/s00467-015-3151-1 -
Romanian Journal of Morphology and... 2017Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert...
Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.
Topics: Acrocephalosyndactylia; Female; Humans; Infant, Newborn; Pregnancy; Reticulocytosis; Syndactyly
PubMed: 28523332
DOI: No ID Found