• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.1
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• pp.44-50
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• 2002

Apert syndrome is a kind of congenital-acrocephalosyndactyly syndrome which was first reported by Apert in 1906 and characterized by its acrocephaly and syndactyly. Clinical characteristic features are cone-shaped skull morphology due to early fusion of coronal suture, fusion of fingers of hands and toes of feet. It is an autosomal dominant-heritable syndrome. Due to hypo-development of midface region, Apert syndrome patients have a tendency to have ocular proptosis, hypertelorism, maxillary deficiency. High palate and soft palate cleft are common findings in these patients. In general, mandibular growth pattern is normal, but relative maxillary deficiency exaggerates mandibular forward position, so relative mandibular prognathism is inevitable. Narrow maxillary and mandibular dental arch worsen teeth alignment and crowding. Skeletal malocclusion and open bite are also common. This is a case report of a Korean 3 year 1 month male Apert syndrome child referred by department of plastic surgeon for the possibility of orthodontic treatment. General features of Apert syndrome, patient's medical history, radiographic evaluation, clinical examination, orthodontic and surgical treatment planning are discussed in this report.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.151-155
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• 2010

Apert syndrome is a rare congenital anomaly characterized by craniofacial malformations and severe symmetrical syndactyly of fingers and toes. This syndrome is caused by a genetic mutation; the S253 mutation is common, though the P253R mutation is not as frequent. Common symptoms include skeletal malformations, poor joint mobility, eye and ear problems, cleft palate, and orthodontic and other dental problems. We report a case of an infant with the common morphological features of Apert syndrome. Interestingly, she was found to have the P253R mutation in FGFR2 exon VIII, which has been less commonly observed in Korea. A brief review of the literature is included.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.3
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• pp.539-547
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• 2008

Apert syndrome is an autosomal dominant condition characterized by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet. It occurs in about 1 of every 65,000 to 160,000 births and is caused by a mutation in the fibroblast growth factor receptor 2(FGFR2) gene. Apert syndrome typically produces acrobrachycephaly(tower skull). The occiput is flattened, and there is a tall appearance to the fore head. Ocular proptosis is a characteristic finding, along with hypertelorism and downward slanting lateral palpebral fissures. The middle third of the face is markedly retruded and hypoplastic, resulting in a relative mandibular prognathism. The reduced size of the nasopharynx and narrowing of the posterior choana can lead to mouth breathing, contributing to an open-mouth apprance. Three fourths of all patients exhibit either a cleft of the soft palate or a bifid uvula. The maxillary hypoplasia leads to a V-shaped arch and crowding of the teeth. A 6-year-old male patient visited to the Department of Pediatric dentistry, Kangnung National University of Dental Hospital. He visited the hospital to get treatment of carious teeth. The purpose of this report is to present a specific dental manifestations about the apert syndrome.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.40.1-40.8
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• 2018

Background: A 9-year-old male showed severe defects in midface structures, which resulted in maxillary hypoplasia, ocular hypertelorism, relative mandibular prognathism, and syndactyly. He had been diagnosed as having Apert syndrome and received a surgery of frontal calvaria distraction osteotomy to treat the steep forehead at 6 months old, and a surgery of digital separation to treat severe syndactyly of both hands at 6 years old. Nevertheless, he still showed a turribrachycephalic cranial profile with proptosis, a horizontal groove above supraorbital ridge, and a short nose with bulbous tip. Methods: Fundamental aberrant growth may be associated with the cranial base structure in radiological observation. Results: The Apert syndrome patient had a shorter and thinner nasal septum in panthomogram, PA view, and Waters' view; shorter zygomatico-maxillary width (83.5 mm) in Waters' view; shorter length between the sella and nasion (63.7 mm) on cephalogram; and bigger zygomatic axis angle of the cranial base (118.2°) in basal cranial view than a normal 9-year-old male (94.8 mm, 72.5 mm, 98.1°, respectively). On the other hand, the Apert syndrome patient showed interdigitating calcification of coronal suture similar to that of a normal 30-year-old male in a skull PA view. Conclusion: Taken together, the Apert syndrome patient, 9 years old, showed retarded growth of the anterior cranial base affecting severe midface hypoplasia, which resulted in a hypoplastic nasal septum axis, retruded zygomatic axes, and retarded growth of the maxilla and palate even after frontal calvaria distraction osteotomy 8 years ago. Therefore, it was suggested that the severe midface hypoplasia and dysostotic facial profile of the present Apert syndrome case are closely relevant to the aberrant growth of the anterior cranial base supporting the whole oro-facial and forebrain development.

• Journal of Korean Neurosurgical Society
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• v.59 no.3
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• pp.187-191
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• 2016

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.

• The korean journal of orthodontics
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• v.33 no.6 s.101
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• pp.485-497
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• 2003

The form and function of the craniofacial structure critically depend on genetic information. With recent advances in the molecular technology, genes that are important for normal growth and morphogenesis of the craniofacial skeleton are being rapidly uncovered, shaping up modem craniofacial biology. One of them is fibroblast growth factor receptor 2 (FGFR2). Specific point mutations in the. FGFR2 gene have been linked to Apert syndrome, which is characterized by premature closure of cranial sutures and craniofacial anomalies as well as limb deformities. To study pathogenic mechanisms underlying craniosynostosis phenotype of Apert syndrome, we used a transgenic approach; an FGFR2 minigene construct containing an Apert mutation (a point mutation that substitute proline at the position 253 to arginine; P253R) was introduced into fertilized mouse germ cells by DNA microinjection. The injected cells were then allowed to develop into transgenic mice. We used a bone-specific promoter (a DNA fragment from the type I collagen gene) to confine the expression of mutant FGFR2 gene to the bone tissue, and asked whether expression of mutant FGFR2 in bone is sufficient to cause the craniosynostosis phenotype in mice. Initial characterization of these mice shows prematurely closed cranial sutures with facial deformities expected from Apert patients. We also demonstrate that the transgene produces mutant FGFR2 protein with increased functional activities. Having this useful mouse model, we now can ask questions regarding the role of FGFR2 in normal and abnormal development of cranial bones and sutures.

• The korean journal of orthodontics
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• v.36 no.4
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• pp.284-294
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• 2006

Objective: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. Methods: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. Results: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. Conclusion: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.

• Archives of Plastic Surgery
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• v.34 no.1
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• pp.64-69
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• 2007

Purpose: The key of treatment in syndactyly is to separate the fused digits safely, and to create a normal web space with enough cutaneous coverage. Despite many techniques have described the correction of syndactyly, skin graft still remains the annoying one. We designed the pentagonal flap from hand dorsum to reconstruct the web space reliably and try to minimize the need for skin graft. Methods: Between July 2003 and August 2005, six cases of syndactyly were corrected at UCLA Medical Center and Hallym University Sacred Heart Hospital using dorsal pentagonal flap for web space reconstruction and straight incisions for the sides of digits to minimize the need for skin graft. The proximal edge of the pentagonal flap was designed in V shape to allow for easy closure of the donor site after advancement. The pentagonal flap was advanced volarly with the underlying dermofat tissues to form a digital web. In some cases, skin defects were unavoidable and covered with full thickness skin graft from the inguinal area. Results: Syndactyly were seen in 4 cases of Apert syndrome, 1 postburn scar webbing with PIP joint contracture and 1 recurrence after the incomplete reconstruction. In all Apert syndrome, straight line incision was used along the sides of the fingers and skin graft was needed. But, in 2 cases of incomplete type, we could save the need for skin graft only for the correction of syndactyly. We could get a good looking web space without any complications such as flap or graft loss. Conclusion: As a modification of Sherif's V-Y dorsal metacarpal flap, we believe pentagonal flap could be one of the easiest and safest way to reconstruct the web space of syndactyly in functional and cosmetic standpoint.

• The Journal of the Korean life insurance medical association
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• v.29 no.2
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• pp.29-32
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• 2010

Moyamoya disease (MMD) is a progressive occlusive disease of the cerebral vasculature with particular involvement of the circle of Willis and the arteries that feed it. MMD is one of cerebrovacular accident,which is treated with sugical maeuver in pediatic neurosurgery. Moyamoya (ie, Japanese for "puff of smoke") characterizes the appearance on angiography of abnormal vascular collateral networks that develop adjacent to the stenotic vessels. The steno-occlusive areas are usually bilateral, but unilateral involvement does not exclude the diagnosis. The exact etiology of moyamoya disease is unknown. Some genetic predisposition is apparent because it is familial 10% of the time. The disease may be hereditary and multifactorial. It may occur by itself in a previously healthy individual. However, many disease states have been reported in association with moyamoya disease, including the following: 1) Immunological - Graves disease/thyrotoxicosis 2) Infections - Leptospirosis and tuberculosis 3) Hematologic disorders - Aplastic anemia, Fanconi anemia, sickle cell anemia, and lupus 4) Congenital syndromes - Apert syndrome, Down syndrome, Marfan syndrome, tuberous sclerosis, Turner syndrome, von Recklinghausen disease, and Hirschsprung disease 5) Vascular diseases - Atherosclerotic disease, coarctation of the aorta and fibromuscular dysplasia, 6)cranial trauma, radiation injury, parasellar tumors, and hypertension etc. These associations may not necessarily be causative but do warrant consideration due to impact on treatment.(Mainly neurosurgical operation.) The incidence of moyamoya disease is highest in Japan. The prevalence of MMD is 1 person per 100,000 population. The prevalence and incidence of moyamoya disease in Japan has been reported to be 3.16 cases and 0.35 case per 100,000 people, respectively. With regard to sex, the female-to-male ratio is 1.4:1. A bimodal peak of incidence is noted, with symptoms occurring either in the first decade(5-10yr) or in the third and fourth decades (30-40yr)of life. Mortality rates of moyamoya disease are approximately 10% in adults and 4.3% in children. Death is usually from hemorrhage. In aspect of life insurance, MR is 1700%, EDR is 16 per 1000 persons. Children and adults with moyamoya disease (MMD) may have different clinical presentations. The symptoms and clinical course vary widely from asymptomatic to transient events to severe neurologic deficits. Adults experience hemorrhage more commonly; cerebral ischemic events are more common in children. Children may have hemiparesis, monoparesis, sensory impairment, involuntary movements, headaches, dizziness, or seizures. Mental retardation or persistent neurologic deficits may be present. Adults may have symptoms and signs similar to those in children, but intraventricular, subarachnoid, or intracerebral hemorrhage of sudden onset is more common in adults. Recently increasing diagnosis of MMD with MRI, followed by surgical operation is noted. MMD needs to be considered as the "CI" state now in life insurance fields.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.1
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• pp.69-77
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• 1996

The midfacial deficiency is usually accompanied with congenital craniofacial synostosis, such as Crouzon, Apert, Pfeiffer, Carpenter, Saethre-Chotzen syndrome, and so on. But sometimes isolated midfacial deficiency without cranial malformations may appeared, the cause of which is congenital, hereditary, or secondary to developmental factors, such as infection and trauma to middle face. Since Sir Harold Gillies reposted the first high maxillary osteotomy that alleviated the problems of total midfacial deficiency, the various operative methods were developed by many clinicians, such as Longacre and Tessier. These procedures can enlarge the orbital volume and decreases exorbitism. As middle face was moved forward, these functional, esthetic, and psychologic advantages were resulted from this. This is a case of midfacial deficiency corrected by the subcranial Le Fort Ⅲ osteotomy through only coronal approach.