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The Journal of the Association of... Sep 2020
Topics: Acrocephalosyndactylia; Case-Control Studies; Humans
PubMed: 32798349
DOI: No ID Found -
NeoReviews Apr 2021Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live...
Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live births. Primary or congenital craniosynostoses represent the majority of cases and consist of single-suture and multisuture synostoses. Multisuture synostoses are typically associated with distinct craniofacial syndromes, including Muenke syndrome, Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, and are thus categorized under syndromic craniosynostoses. Secondary causes of craniosynostoses include metabolic or hematologic disorders that affect bone metabolism and typically present much later than primary synostoses. The severity of the deformity and the presence of increased intracranial pressure dictate the need for early surgical intervention, prompting the importance of early recognition and timely referral. Infants with craniosynostosis are also at increased risk for neurodevelopmental impairment and thus require close follow-up and monitoring. The early recognition and referral of craniosynostosis is imperative for the optimization of management and minimization of potential neurologic impairments that may develop.
Topics: Craniofacial Dysostosis; Craniosynostoses; Humans; Infant, Newborn; Skull; Syndrome
PubMed: 33795400
DOI: 10.1542/neo.22-4-e250 -
Facial Plastic Surgery Clinics of North... Nov 2016Syndromic craniosynostosis affects up to 1:30,000 live births with characteristic craniofacial growth restrictions, deformities, and other associated abnormalities, such... (Review)
Review
Syndromic craniosynostosis affects up to 1:30,000 live births with characteristic craniofacial growth restrictions, deformities, and other associated abnormalities, such as carpal-pedal anomalies and cognitive function impairment. More than 150 syndromes are associated with craniosynostosis. This article describes some commonalities and distinguishing features and management of syndromic synostosis. Also addressed is secondary synostosis, which is often found in syndromic children with problems related to microcephaly, hydrocephalus, or shunt-induced craniosynostosis, although pathophysiologically and genetically different. The importance of obtaining a thorough history and a complete physical and examination is highlighted. Adjuvant testing and multidisciplinary management are discussed.
Topics: Craniofacial Dysostosis; Craniosynostoses; Humans; Osteogenesis, Distraction; Syndrome
PubMed: 27712819
DOI: 10.1016/j.fsc.2016.06.008 -
Nature Medicine Mar 2019Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus. However, screening for many dominant monogenic...
Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus. However, screening for many dominant monogenic disorders associated with de novo mutations is not available, despite their relatively high incidence. Here we report on the development and validation of, and early clinical experience with, a new approach for non-invasive prenatal sequencing for a panel of causative genes for frequent dominant monogenic diseases. Cell-free DNA (cfDNA) extracted from maternal plasma was barcoded, enriched, and then analyzed by next-generation sequencing (NGS) for targeted regions. Low-level fetal variants were identified by a statistical analysis adjusted for NGS read count and fetal fraction. Pathogenic or likely pathogenic variants were confirmed by a secondary amplicon-based test on cfDNA. Clinical tests were performed on 422 pregnancies with or without abnormal ultrasound findings or family history. Follow-up studies on cases with available outcome results confirmed 20 true-positive, 127 true-negative, zero false-positive, and zero-false negative results. The initial clinical study demonstrated that this non-invasive test can provide valuable molecular information for the detection of a wide spectrum of dominant monogenic diseases, complementing current screening for aneuploidies or carrier screening for recessive disorders.
Topics: Abnormalities, Multiple; Achondroplasia; Acrocephalosyndactylia; Adult; Bone and Bones; Cell-Free Nucleic Acids; Collagen Type I; Collagen Type I, alpha 1 Chain; De Lange Syndrome; Female; Genetic Diseases, Inborn; High-Throughput Nucleotide Sequencing; Humans; Hydrops Fetalis; Lymphangioma, Cystic; Nuchal Translucency Measurement; Osteogenesis Imperfecta; Predictive Value of Tests; Pregnancy; Prenatal Diagnosis; Sequence Analysis, DNA; Thanatophoric Dysplasia; Ultrasonography, Prenatal
PubMed: 30692697
DOI: 10.1038/s41591-018-0334-x -
Journal of Developmental Biology Aug 2022Apert syndrome is a rare genetic disorder characterized by craniosynostosis, midface retrusion, and limb anomalies. Cleft palate occurs in a subset of Apert syndrome... (Review)
Review
Apert syndrome is a rare genetic disorder characterized by craniosynostosis, midface retrusion, and limb anomalies. Cleft palate occurs in a subset of Apert syndrome patients. Although the genetic causes underlying Apert syndrome have been identified, the downstream signaling pathways and cellular mechanisms responsible for cleft palate are still elusive. To find clues for the pathogenic mechanisms of palatal defects in Apert syndrome, we review the clinical characteristics of the palate in cases of Apert syndrome, the palatal phenotypes in mouse models, and the potential signaling mechanisms involved in palatal defects. In Apert syndrome patients, cleft of the soft palate is more frequent than of the hard palate. The length of the hard palate is decreased. Cleft palate is associated most commonly with the S252W variant of FGFR2. In addition to cleft palate, high-arched palate, lateral palatal swelling, or bifid uvula are common in Apert syndrome patients. Mouse models of Apert syndrome display palatal defects, providing valuable tools to understand the underlying mechanisms. The mutations in FGFR2 causing Apert syndrome may change a signaling network in epithelial-mesenchymal interactions during palatogenesis. Understanding the pathogenic mechanisms of palatal defects in Apert syndrome may shed light on potential novel therapeutic solutions.
PubMed: 35997397
DOI: 10.3390/jdb10030033 -
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 -
Biomedicines Nov 2021Abnormal mosaicism is the coexistence of cells with at least two genotypes, by the time of birth, in an individual derived from a single zygote, which leads to a disease... (Review)
Review
Abnormal mosaicism is the coexistence of cells with at least two genotypes, by the time of birth, in an individual derived from a single zygote, which leads to a disease phenotype. Somatic mosaicism can be further categorized into segmental mosaicism and nonsegmental somatic mosaicism. Acne is a chronic illness characterized by inflammatory changes around and in the pilosebaceous units, commonly due to hormone- and inflammatory signaling-mediated factors. Several systemic disorders, such as congenital adrenal hyperplasia, polycystic ovarian syndrome, and seborrhoea-acne-hirsutism-androgenetic alopecia syndrome have classically been associated with acne. Autoinflammatory syndromes, including PAPA, PASH, PAPASH, PsAPASH, PsaPSASH, PASS, and SAPHO syndromes include acneiform lesions as a key manifestation. Mosaic germline mutations in the gene have been associated with Apert syndrome and nevus comedonicus, two illnesses that are accompanied by acneiform lesions. In this review, we summarize the concept of cutaneous mosaicism and elaborate on acne syndromes, as well as acneiform mosaicism.
PubMed: 34829964
DOI: 10.3390/biomedicines9111735