-
Current Opinion in Pediatrics Dec 2017When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may... (Review)
Review
PURPOSE OF REVIEW
When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis.
RECENT FINDINGS
Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases. The substantial contributions of mutations in two genes, TCF12 and ERF, is confirmed. Important recent discoveries are mutations of CDC45 and SMO in specific craniosynostosis syndromes, and of SMAD6 in nonsyndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted.
SUMMARY
Strategies to optimize clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. In addition to improved genetic counseling, recent discoveries spotlight the important roles of signaling through the bone morphogenetic protein and hedgehog pathways in cranial suture biogenesis, as well as a key requirement for adequate cell division in suture maintenance.
Topics: Craniosynostoses; Genetic Counseling; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Mutation; Exome Sequencing
PubMed: 28914635
DOI: 10.1097/MOP.0000000000000542 -
American Journal of Human Genetics Sep 2015Craniosynostosis, the premature fusion of one or more cranial sutures of the skull, provides a paradigm for investigating the interplay of genetic and environmental... (Review)
Review
Craniosynostosis, the premature fusion of one or more cranial sutures of the skull, provides a paradigm for investigating the interplay of genetic and environmental factors leading to malformation. Over the past 20 years molecular genetic techniques have provided a new approach to dissect the underlying causes; success has mostly come from investigation of clinical samples, and recent advances in high-throughput DNA sequencing have dramatically enhanced the study of the human as the preferred "model organism." In parallel, however, we need a pathogenetic classification to describe the pathways and processes that lead to cranial suture fusion. Given the prenatal onset of most craniosynostosis, investigation of mechanisms requires more conventional model organisms; principally the mouse, because of similarities in cranial suture development. We present a framework for classifying genetic causes of craniosynostosis based on current understanding of cranial suture biology and molecular and developmental pathogenesis. Of note, few pathologies result from complete loss of gene function. Instead, biochemical mechanisms involving haploinsufficiency, dominant gain-of-function and recessive hypomorphic mutations, and an unusual X-linked cellular interference process have all been implicated. Although few of the genes involved could have been predicted based on expression patterns alone (because the genes play much wider roles in embryonic development or cellular homeostasis), we argue that they fit into a limited number of functional modules active at different stages of cranial suture development. This provides a useful approach both when defining the potential role of new candidate genes in craniosynostosis and, potentially, for devising pharmacological approaches to therapy.
Topics: Animals; Brain; Cell Lineage; Cranial Sutures; Craniosynostoses; Humans; Mice; Models, Biological; Osteogenesis; Phenotype; Risk Factors
PubMed: 26340332
DOI: 10.1016/j.ajhg.2015.07.006 -
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 -
Hand (New York, N.Y.) Dec 2016Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral pectoral muscle agenesis and ipsilateral hand deformity.... (Review)
Review
Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral pectoral muscle agenesis and ipsilateral hand deformity. A comprehensive review of the medical literature on Poland anomaly was performed using a Medline search. Poland anomaly is a sporadic, phenotypically variable congenital condition usually characterized by unilateral, simple syndactyly with ipsilateral limb hypoplasia and pectoralis muscle agenesis. Operative management of syndactyly in Poland anomaly is determined by the severity of hand involvement and the resulting anatomical dysfunction. Syndactyly reconstruction is recommended in all but the mildest cases because most patients with Poland anomaly have notable brachydactyly, and digital separation can improve functional length. Improved understanding the etiology and presentation of Poland anomaly can improve clinician recognition and management of this rare congenital condition.
Topics: Brachydactyly; Hand Deformities, Congenital; Humans; Pectoralis Muscles; Phenotype; Poland Syndrome; Syndactyly
PubMed: 28149203
DOI: 10.1177/1558944716647355 -
Anales de Pediatria (Barcelona, Spain :... Jul 2017
Topics: Craniosynostoses; Humans; Infant; Phenotype
PubMed: 27106663
DOI: 10.1016/j.anpedi.2016.02.005 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2018Craniosynostosis (CS) is a complex condition consisting of the early fusion of one or more cranial sutures in the intrauterine stage. The affected infant exhibits... (Review)
Review
BACKGROUND
Craniosynostosis (CS) is a complex condition consisting of the early fusion of one or more cranial sutures in the intrauterine stage. The affected infant exhibits abnormal head shape at time of birth or shortly thereafter. It can be observed in normal individuals (non-syndromic CS or NSCS) or as a part of a multisystem syndrome. The purposes of the present article were to carry out a scoping review on Non-Syndromic CS and to discuss the most important findings retrieved.
MATERIAL AND METHODS
The steps of this scoping review were as follows: first, to pose a research question; second, to identify relevant studies to answer the research question; third, to select and retrieve the studies; fourth, to chart the critical data, and finally, to collate, summarize, and report the results from the most important articles. Relevant articles published over a 20-year period were identified and retrieved from five Internet databases: PubMed; EMBASE; Cochrane Library; Google Scholar, and EBSCO.
RESULTS
Fourteen articles were finally included in the present scoping review. The following four most important clinical issues are discussed: (i) normal cranial development, clinical manifestations, and pathogenesis of NCSC; (ii) clinical evaluation of NCSC; (iii) treatment and post-surgical follow-up; and (iv) additional considerations.
CONCLUSIONS
NSCS may be present with associated head shapes. Multiple early surgical reconstructive options are currently available for the disorder. Pediatric Dentistry practitioners must be familiarized with this condition and form part of a multi-approach health team as those responsible for the opportune oral health care of the affected child.
Topics: Child; Craniosynostoses; Humans
PubMed: 29924758
DOI: 10.4317/medoral.22328 -
European Journal of Medical Genetics Jun 2021This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the... (Review)
Review
This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field.
Topics: Bibliometrics; Biomedical Research; Craniosynostoses; Genetics, Medical; Humans; Periodicals as Topic
PubMed: 33866005
DOI: 10.1016/j.ejmg.2021.104224 -
Journal of Medical Genetics May 2024Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies... (Review)
Review
Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (, ) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: ; RTS2: ), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.
Topics: Rubinstein-Taybi Syndrome; Humans; CREB-Binding Protein; E1A-Associated p300 Protein; Consensus; Disease Management; Mutation
PubMed: 38471765
DOI: 10.1136/jmg-2023-109438 -
Child's Nervous System : ChNS :... Oct 2021The enlargement of the posterior cranial fossa volume is considered one of the main steps of the surgical management of children with multiple sutures craniosynostosis.... (Review)
Review
BACKGROUND
The enlargement of the posterior cranial fossa volume is considered one of the main steps of the surgical management of children with multiple sutures craniosynostosis. Different management options have been proposed including fixed expansive craniotomy, free bone flap craniotomy, and distraction osteogenesis.
OBJECTIVES
To review indications to "free bone flap" craniotomy for the posterior fossa expansion, detailing advantages, disadvantages, and complications related to the technique.
RESULTS AND CONCLUSIONS
A review of the literature shows that "free bone flap" posterior expansion cranioplasty still has a role, particularly in infants with thin and "honeycomb" structure of the bone, allowing to gain adequate intracranial volume increases and to postpone to a more adequate time surgery aimed at anterior cranial fossa expansion.
Topics: Child; Craniosynostoses; Craniotomy; Humans; Infant; Osteogenesis, Distraction; Skull; Surgical Flaps
PubMed: 34268594
DOI: 10.1007/s00381-021-05281-x -
The Pan African Medical Journal 2015
Topics: Adolescent; Back Pain; Humans; Male; Poland Syndrome
PubMed: 26587143
DOI: 10.11604/pamj.2015.21.294.7599