Genetic Syndromes Associated with Craniosynostosis

Ko, Jung Min The Korean Neurosurgical Society 2016 Journal of Korean neurosurgical society Vol.59 No.3

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.

Automatical Cranial Suture Detection based on Thresholding Method

Park, Hyunwoo,Kang, Jiwoo,Kim, Yong Oock,Lee, Sanghoon International Society for Simulation Surgery 2015 Journal of International Society for Simulation Su Vol.2 No.1

Purpose The head of infants under 24 months old who has Craniosynostosis grows extraordinarily that makes head shape unusual. To diagnose the Craniosynostosis, surgeon has to inspect computed tomography(CT) images of the patient in person. It's very time consuming process. Moreover, without a surgeon, it's difficult to diagnose the Craniosynostosis. Therefore, we developed technique which detects Craniosynostosis automatically from the CT volume. Materials and Methods At first, rotation correction is performed to the 3D CT volume for detection of the Craniosynostosis. Then, cranial area is extracted using the iterative thresholding method we proposed. Lastly, we diagnose Craniosynostosis by analyzing centroid relationships of clusters of cranial bone which was divided by cranial suture. Results Using this automatical cranial detection technique, we can diagnose Craniosynostosis correctly. The proposed method resulted in 100% sensitivity and 90% specificity. The method perfectly diagnosed abnormal patients. Conclusion By plugging-in the software on CT machine, it will be able to warn the possibility of Craniosynostosis. It is expected that early treatment of Craniosynostosis would be possible with our proposed algorithm.

두개골 조기유합증 환자의 술후 CT Scan을 이용한 두개강내 용적의 평가

김석권,이장호,한재정,정기환,이근철,박정민,Kim, Seok Kwun,Lee, Jang Ho,Han, Jae Jung,Jung, Ki Hwan,Lee, Keun Cheol,Park, Jung Min 대한성형외과학회 2005 Archives of Plastic Surgery Vol.32 No.1

Craniosynostosis is the premature fusion of one or more sutures of either cranial vault or base. Fused sutures may impede normal growth of the calvaria, leading to characteristic skull deformities; Morphological craniosynostosis is classified descriptively. Being craniosynostosis uncorrected the deformity progresses continuously and causes an increase of intracranial pressure. The surgical involvement aims at the expansion of intracranial space as well as satisfactory achievement of craniofacial shape. Early surgical correction in infancy prevents the deformity from the further progression and possible associated complication of high intracranial pressure. A long period of follow-up is essential to asses the outcome of an effectiveness of the surgery. measurement of intracranial volume has been concerned in medical personnel and anthropologists for many years. A reliable and accurate measurements of the intracranial volume facilitates to make a diagnosis and treatment of craniosynostosis. Pre-and postoperative change of intracranial volume was evaluated with 3D CT scanning in 12 cases of craniosynostosis who underwent frontal advancement and total cranial vault remodeling. Increased intracranial volume is attributed to surgical release of craniosynostosis and natural growth. We conceive that the intracranial volume is significantly increased after surgical correction of fused cranial sutures and along with natural growing. A procedure of frontal advancement and total cranial vault remodeling is very useful to correct such a deformity as craniosynostosis. And also 2 cases out of five mentally retarded patients improved remarkably and Forehead retrusion or temporal depression followed in another two cases.

두개골 조기유합증의 수술적 교정에서 BoneSource?의 보조적 사용

임지현,송진경,유결,변준희 대한성형외과학회 2005 Archives of Plastic Surgery Vol.32 No.4

Craniosynostosis is a congenital anomaly characterized by premature closure of cranial sutures. Surgical intervention should be performed during infancy. However, surgical correction of craniosynostosis remains bone defect and secondary angle occasionally. Currently, publications investigating solutions to bone defect and secondary angle created by cranioplasty are getting much interest. We have used BoneSource which is relatively safe as an implantable substance for providing solutions for this problem. From June 2002 to January 2004, five children with craniosynostosis underwent frontocalvarial contouring using BoneSource and concurrent cranial vault remodeling. The patient ages ranged from 8.0 months to 4.9 years(mean, 2.5 years). The quantity of BoneSource implanted ranged from 10 to 25g, with a mean of 13g. This paper presents the first series of children treated with BoneSource for frontocalvarial contouring in the surgical correction of craniosynostosis. No patients experienced any complications. Our results shows excellent retention of contour without causing asymmetry or irregularity. No visible evidence of interference with craniofacial growth were observed. Through our experiences, BoneSource is found to be very useful for frontocalvarial contouring in children undergoing correction of craniosynostosis.

벤츠 패턴을 가진 두개골 조기 유합증: 증례보고

류석태,임소영,문구현 대한성형외과학회 2011 Archives of Plastic Surgery Vol.38 No.5

Purpose: Craniosynostosis of three or more cranial sutures was not common. "Mercedes Benz pattern,"named by Moore1 was a rare form of craniosynostosis and had an atypical pattern of premature closure of cranial suture. It was not reported in Republic of Korea. We report this case with literature review. Methods: A 13-months-old male patient visited our clinic due to exophthalmos. He showed normal developmental course. Other neurological tests were normal but he was Crouzon syndrome patient. CT scans showed bilateral lambdoid and posterior sagittal sutures were fused and the length of the skull was extended. Cranioplasty with pi craniotomy & Barrel-Stave osteotomy and recombination of the bone flap was performed. Results: The patient was discharged after post operative 10 days without any complications. In follow up visit after 2.7 years, he was in good state without recurrence and functional abnormality of skull. Conclusion: This was the first case of Mercedes Benz pattern craniosynostosis with Crouzon syndrome in Korea. This type of craniosynostosis has to be considered differently from single type of craniosynostosis or typical syndromic craniosynostosis clinically and surgically.

두개골 신연술 후 신연된 골조직의 성장

김용욱,김한조,유선국,김희중,김기덕,박병윤 대한성형외과학회 2004 Archives of Plastic Surgery Vol.31 No.5

The pathogenesis of craniosynostosis is the early bone fusion of the sutures. Conventional treatment focused on creating a bony gap in which distraction osteogenesis could be a contradictive procedure. There are few reports on the long-term follow-up of distraction in craniosynostosis and into the continuity of bone tissue. This study was performed to investigate if this continuity of the regenerated bone tissue, which can possibly have inhibitory potentials for bone growth, affects growth after distraction osteogenesis with long- term follow-up results. For the study, the authors realigned all CT scans into a same position using a software program using landmarks from the image for comparison in terms of growth ratio for patients with craniosynostosis. From January 2000 to October 2002, the authors performed distraction osteogenesis on 5 patients with craniosynostosis. Three patients had unilateral coronal craniosynostotis and 2 with unilambdoidal craniosynostosis. The follow-up period was from 13 months to 33 months after full distraction. 3D CT images were obtained preoperatively, after full distraction and at the last follow-up. The result was that the regenerated calvarial bone seems to grow in the same growth ratio as the normal side up to 2 years on follow-up in the patient with unilateral craniosynostosis. According to these results, we conclude that the regenerated bone grows as normal bone even after distraction osteogenesis.

단순 대칭성 두개골 조기유합증 환자에서의 전두 두개골 재배치술을 위한 새로운 절골술-The Bull's Osteotomy

박병윤,김성민,유대현 大韓成形外科學會 1999 Archives of Plastic Surgery Vol.26 No.5

Cranocsynostosis is the term that designates premature fusion of one or more sutures in either the cranial vault or cranial base. Especially scaphocephaly, brachycephaly and trigonocephaly are included in simple symmetric craniosynostosis. In simple symmetric craniosynostosis, the functional deformity is rare, but deformity in external appearance is always a serious problem. The purpose of forehead reshaping in simple symmetric craniosynostosis is recovery of normal cerebral growth and improvement of cranial cosmetic problem by restoration of normal calvarial anatomic structure. Various surgical methods have Bbeen developed in an effort to correct craniosynostosis. Cranial vault remodeling with or without supraorbital band advancement is a widely accpeted method of correcting simple symmetric craniosynostosis. However, the standardized surgical method has not yet been estabilished in reshaping the forehead during cranial vault remodeling of simple symmetric craniosynostosis. The authors developed a new osteotomy method, the bull's osteotomy, which is a limited osteotomy for cranial vault remodeling. It produces posterior tilting of a prominant forehead as well as increased biparietotemporal distance for effective forehead reshaping. We applied this techriaue in 8 scaphocephaly and 2 brachycephaly patients under 5 years of age who have not yet reached bony consolidation. All patinets obtained satisfactory results with properly corrected deformity and no relapse was observed during the follow-up period. This new osteotomy method is simple and effective and a consistant surgical outcome is expected. particularly the contour of the forehead on the frontotemporal area is corrected to have a smooth and natural curvature. Based on our experience using bull's osteotomy, we offer this new surgical technique for managing simple symmetric cranoisynostosis patients.

Current and Future Perspectives in Craniosynostosis

Kang, Seok-Gu,Kang, Joon-Ki The Korean Neurosurgical Society 2016 Journal of Korean neurosurgical society Vol.59 No.3

Craniosynostosis has a varied clinical spectrum, ranging from isolated single suture involvement to multi-sutural fusions. Greater understanding of the pathogenesis of craniosynostosis has led to the development of practical treatment protocols. Three stages of growth have determined the approach to managing craniosynostosis : the early period, up to 12 months; the intermediate period, from 1 to 10 years; and the late period, beginning at 10 years. This review discusses current surgical management and future perspectives in craniosynostosis.

두개골 조기유합증의 수술적 치료

최중언,김영수,정상섭,이규창 대한신경외과학회 1983 Journal of Korean neurosurgical society Vol.12 No.4

Authors made a clinical analysis on 22 patients of craniosynostosis who had been treated surgically at Severance Hospital from Jan. 1975 to Jun. 1983 and the results were summarized as follows. 1) In analysis of type of craniosynostosis, all of patient showed synostosis of coronal suture : 7 cases had simple involvement of coronal suture, 14 cases had multiple suture involvement and 1 Crouzen's disease. 2) In sex distribution, male were 13 and female were 9 cases. Patient who had been on early operation within 6 months after birth were 6 cases (27%). 3) The most common clinical symptoms on admission were mental and developmental retardation and most patient showed palpable ridge along the suture of synostosis. 4) In brain CT scan finding, ventricular dilatation, cortical atrophy, low density areas and subdural effusion were commonly found in cases who diagnosis and operation were delayed. These findings were thought to be the secondary effect of increased intracranial pressure in early stage of craniosynostosis. 5) Among several operative methods, lateral canthal advancement of supraorbital margin showed good surgical results to provide adequate expansion of frontal bone. Early operation also revealed good results. 6) To make an early detection of craniosynostosis it will be necessary to give pediatricians and general practitioners more information about this disease.

Functional characterization of a novel FGFR2 mutation, E731K, in craniosynostosis

Park, Jounghyen,Park, Ok‐,Jin,Yoon, Won‐,Joon,Kim, Hyun‐,Jung,Choi, Kang‐,Young,Cho, Tae‐,Joon,Ryoo, Hyun‐,Mo Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of cellular biochemistry Vol.113 No.2

<P><B>Abstract</B></P><P>Craniosynostosis is a condition in which some or all of the sutures in the skull of an infant close prematurely. Fibroblast growth factor receptor 2 (FGFR2) mutations are a well‐known cause of craniosynostosis. Many syndromes that comprise craniosynostosis, such as Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, have one of the phenotypes that have been reported in FGFR2 mutant patients. FGFRs have been reported in four types (FGFR1–4), and upon binding with FGF ligands, signal transduction occurs inside of cells. Activated FGFR stimulates an osteogenic master transcription factor, Runx2, through the MAP kinase and PKC pathways. We obtained a genetic analysis of six Korean patients who have craniosynostosis as a phenotype. All of the patients had at least one mutation in the FGFR2 gene; five of those mutations have already been reported elsewhere, while one mutation is novel and was hypothesized to lead to Apert syndrome. In this study, we reported and functionally analyzed a novel mutation of the FGFR2 gene found in a craniosynostosis patient, E731K. The mutation is in the 2nd tyrosine kinase domain in the C‐terminal cytoplasmic region of the molecule. The mutation caused an enhanced phosphorylation of the FGFR2<SUP>E731K</SUP> and ERK‐MAP kinase, the stimulation of transcriptional activity of Runx2, and consequently, the enhancement of osteogenic marker gene expression. We conclude that the substitution of E731K in FGFR2 is a novel mutation that resulted in a constitutive activation of the receptor and ultimately resulted in premature suture obliteration. J. Cell. Biochem. 113: 457–464, 2012. © 2011 Wiley Periodicals, Inc.</P>