Genetic advances in craniosynostosis

Lattanzi, Wanda; Barba, Marta; Pietro, Lorena Di; Boyadjiev, Simeon A.

doi:10.1002/ajmg.a.38159

Cited by 90 publications

(92 citation statements)

References 293 publications

(470 reference statements)

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“…1, there are six genes frequently (each >0.5% overall) mutated in craniosynostosis: FGFR2 , FGFR3 , TWIST1 , EFNB1 , TCF12 and ERF . Mutations in the first four of these mostly cause recognisable syndromes ( FGFR2 , predominantly Apert, Crouzon and Pfeiffer; FGFR3 , Muenke and Crouzon with acanthosis nigricans; TWIST1 , Saethre-Chotzen; and EFNB1 , craniofrontonasal syndrome), for which the molecular basis was determined a decade or more ago, so their clinical features and genotype-phenotype correlations are largely well documented [3–6]. Recent clinical updates have been published on prevalence of tracheal cartilaginous sleeve [15] and progressive postnatal pansynostosis [16] in syndromic craniosynostosis, both of which highlight the particularly high burden of complications arising from FGFR2 mutations.…”

Section: Syndromic Craniosynostosismentioning

confidence: 99%

“…Fifty-seven genes were classified as validated “craniosynostosis genes” by Twigg and Wilkie [3], based on identification of mutations in two or more independent cases, and some additional potentially causative genes were highlighted by Lattanzi et al [6]. The long tail of rare genetic diagnoses is apparent in Fig.…”

Section: Molecular Diagnostic Approach To Craniosynostosismentioning

confidence: 99%

“…Awareness of both the striking pathological differences between fusion of different cranial sutures, and the complex interplay of potentially causative factors - intrauterine environment, polygenic background, growth and development of the brain, as well as specific monogenic and chromosomal disorders – is essential [3]. Reviews of the clinical approach to diagnosis and associated phenotypic features are covered in several articles [4–6]; here we focus on recent progress in understanding the genetic underpinnings of craniosynostosis.…”

Section: Introductionmentioning

confidence: 99%

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Clinical genetics of craniosynostosis

Wilkie

Johnson²,

Wall³

2017

Current Opinion in Pediatrics

156

169

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Purpose of review When providing accurate clinical diagnosis and genetic counselling 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 non-syndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted. Summary Strategies to optimise clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. As well as improved genetic counselling, recent discoveries spotlight the important roles of signalling 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.

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Section: Syndromic Craniosynostosismentioning

confidence: 99%

Section: Molecular Diagnostic Approach To Craniosynostosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical genetics of craniosynostosis

Wilkie

Johnson²,

Wall³

2017

Current Opinion in Pediatrics

156

169

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“…GLI3 is implicated in a craniofacial syndrome involving cognitive impairment both in humans (Greig cephalopolisyndactily, OMIM #175700) and in mice [Veis tinen et al, 2012;Tabler et al, 2016;Lattanzi et al, 2017] with cognitive impairment, which entails language delay [McDonald-McGinn et al, 2010;Lattanzi, 2016]. Indeed, it regulates skull development acting on the DLX5/RUNX2 cascade , and hence it is expected to have played a role in the physiological events leading to globularization, in which these genes were seemingly involved [Boeckx and Benítez-Burraco, 2014a]; nearly 98% of Altaic Neanderthals and Denisovans gained a nonsynonymous change in GLI3 that is described as mildly disruptive [Castellano et al, 2014].…”

Section: Sz and (The Evolution Of) Human Languagementioning

confidence: 99%

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

et al. 2017

Self Cite

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Schizophrenia (SZ) is a pervasive neurodevelopmental disorder that entails social and cognitive deficits, including marked language problems. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, for unclear reasons. It has been hypothesized that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history, and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this hypothesis, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behavior and cognition, and to favor the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% of SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the domestication syndrome and primarily involving the neural crest.

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“…Single gene mutations, particularly mutations in the FGFR2 , FGFR3 , TWIST1 , and EFNB1 genes, are often detected in syndromic craniosynostosis (Wilkie et al, ). Similarly, a variety of recurrent cytogenetically visible and submicroscopic chromosomal aberrations have been identified in patients with syndromic craniosynostosis (Lattanzi, Barba, Di Pietro, & Boyadjiev, ). Additionally, there are a number of less common genetic mutations and chromosomal rearrangements comprising a percentage of the diagnoses, but their role and impact in the diagnosis evaluation of craniosynostosis continues to be explored (Lattanzi et al, ; Miller et al, ; Wilkie et al, ).…”

Section: Phenotype and Cytogenetic Abnormalities Detected In 10 Indivmentioning

confidence: 98%

Less common underlying genetic diagnoses found in a cohort of 139 individuals surgically corrected for craniosynostosis

Ittleman

Mckissick

Bosanko

et al. 2017

American J of Med Genetics Pt A

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Craniosynostosis is the premature ossification and fusion of one or more cranial sutures. It is one of the most common craniofacial anomalies, occurring in one in 2,000-2,500 births (Boulet, Rasmussen, & Honein, 2008). The multifactorial etiology of craniosynostosis involving both genetic and environmental factors results in a heterogeneous group of disorders (Heuze, Holmes, Peter, c Denominator represents those with phenotypic features described. ITTLEMAN ET AL. | 489 and maxilla-facial computed-tomography (CT) scans revealed metopic craniosynostosis while his alkaline phosphatase levels were low (49, Normal 129-291 U/L). ALPL gene sequencing confirmed the clinical suspicion of hypophosphatasia (HPP) (compound heterozygous c.526G>A/c.1250A>G, p.(Ala176Thr)/p.(Asn417Ser)) and CVR was performed at 18 months of age prior to initiation of enzyme replacement therapy. Craniosynostosis is a known feature of HPP, particularly the infantile type (Mornet, 2007). Individual CS#50 was first evaluated in the neonatal period for craniofacial dysmorphism and skeletal anomalies. Radiographic images documented markedly advanced bone age, widening of the proximal and middle phalanges, and severe cervical spinal stenosis. This patient underwent CVR for sagittal suture synostosis and posterior laminectomies of C3-C4 for cervical stenosis at 2 and 4 years of age, respectively. Over time, the patient was noted to have a flat midface, prominent forehead, full lips, and shallow orbits. The clinical diagnosis of Marshall-Smith syndrome was made and while molecular cytogenetic microarray was normal, sequencing of the NFIX gene could not be conducted. Craniosynostosis was reported in 5/38 (13%) of patients with Marshall-Smith syndrome in a previous study (Shaw et al., 2010).The implications of genetic testing have impact on the surgeon's discussion with the family prior to discussing surgical repair. It is well known, for example, that children with syndromic craniosynostosis tend to have higher relapse rates of their cranial dysmorphology, increased intra-cranial pressure and higher re-operative rates that their non-syndromic cohorts (Esparza et al., 2008;McCarthy et al., 1995). In agreement with a previous report of a large cohort of children with surgically repaired craniosynostosis, in this study, when comparing individuals with proven syndromic craniosynostosis to all others, there was a higher rate of multiple sutures affected (70 vs. 17%, p = < 0.000001) and need for several surgical procedures (48 vs. 25%, p = < 0.05), most of which were invasive ( Supplementary Table S3) (Wilkie et al., 2010). Likewise, the overall rates of suspicion for syndromic craniosynostosis (56/139, 40%) and identified underlying genetic diagnoses (27/56, 48%) are comparable to previous data by Wilkie et al. (2010) of 37% (122/326) and 60% (73/122), respectively. The present study does have some limitations. While a systematic evaluation was conducted by the initial provider evaluating the individual with craniosynostosis, a genetic evaluation was not ...

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Genetic advances in craniosynostosis

Cited by 90 publications

References 293 publications

Clinical genetics of craniosynostosis

Clinical genetics of craniosynostosis

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Less common underlying genetic diagnoses found in a cohort of 139 individuals surgically corrected for craniosynostosis

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