The Journal of Craniofacial Surgery Volume 28, Number 3, May 2017 Brief Clinical Studies anterolateral site. According to the imaging findings, it was thought PATIENT that our lesion was of benign origin and may either be a polyp or a The patient was a 25-year-old male with a diagnosis of WS. His hemangioma. Since the lesion invaded the orbital fossa thereby diagnosis was previously confirmed with fluorescent in situ causing visual problems, the orbital extension of the polyp and the hybridization technique showing at chromosome other components were fully removed via surgical intervention. 7q11.23. On physical inspection, he had most of the characteristic features of WS such as bitemporal hollowing, teeth abnormalities, REFERENCES class III malocclusion, a long philtrum, prominent lips, and blue 1. Bateman ND, Fahy C, Woolford TJ. Nasal polyps: still more questions eyes with starry pattern. His past medical history was also than answers. J Laryngol Otol 2003;117:1–9 significant for supravalvular aortic stenosis and visuospatial 2. Hulse KE, Stevens WW, Tan BK, et al. Pathogenesis of nasal polyposis. disabilities. Clin Exp Allergy 2015;45:328–346 He had an ulcer in his mouth next to the lower left third molar 3. Bachert C, Gevaert P, Holtappels G, et al. Nasal polyposis: from cytokines tooth for the past 2 years. Maxillofacial computed tomography to growth. Am J Rhinol 2000;14:279–290 revealed a mass of 30 25 37 mm in the left ramus of the 4. Cetinkaya EA. Giant antrochoanal polyp in an elderly patient: case report. Acta Otorhinolaryngol Ital 2008;28:147–149 mandible. An incisional biopsy of the mass located in the left 5. Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on retromolar trigone confirmed the diagnosis of ameloblastoma. rhinosinusitis and nasal polyps 2012. Rhinol Suppl 2012;3:1–298 Segmental mandibulectomy for tumor resection was performed. 6. Salaria N, Sharma N, Garg U, et al. Inflammatory septal nasal polyp. Iran The remaining mandible was reconstructed with osseocutaneous J Otorhinolaryngol 2015;27:319–323 fibular flap in a standard fashion (Fig. 1). 7. Dimitrijevic´ MV, Arsovic´ NA, Dudvarski ZR, et al. Giant destructive Both intraoperative and postoperative courses were uneventful. sinonasal polyposis. Srp Arh Celok Lek 2015;143:186–189 Histological analysis of the tumor was consistent with the diagnosis 8. Chobillion MA, Jankowski R. Relationship between mucoceles, nasal of ameloblastoma. The patient tolerated the surgery well and was polyposis and nasalisation. Rhinology 2004;43:219–224 discharged on postoperative day 7. 9. Chung SK, Chang BC, Dhong HJ. Surgical, radiologic, and histologic findings of the antrochoanal polyp. Am J Rhinol 2002;16:71–76 DISCUSSION The literature contains at least 15 published reports of malignancy in patients with WS, including 9 NHL, 2 astrocytoma, 1 ovarian cyst adenoma, 1 acute lymphoblastic , 1 cutaneous fibrous hamartoma, and 1 esophageal carcinoma.3,4 However, the patient Ameloblastoma in a Patient described in this paper is the first WS patient reported with ameloblastoma. With Williams Syndrome and William syndrome occurs as a result of a hemizygous micro- deletion at 7q11.23. The loss of , which is the most Use of Fibular Flap prominent gene located in this locus, contributes to some of the Fatma Betul Tuncer, MD, Bulent Sacak, MD, characteristic features of the WS such as supravalvular aortic Zeynep Deniz Akdeniz, MD, and Ozhan Celebiler, MD stenosis and facial dysmorphism. Elastin is also found in the muscular layer of arteries, and together with collagen and smooth muscle, it determines the stiffness of blood vessels.5 Although the Williams syndrome (WS, also known as Williams–Beuren syndrome) is a caused by a deletion of large gene locus at chromosome 7q11.23. Its incidence is estimated from 1 in 20,000 to 1 in 50,000.1 Williams syndrome is characterized by supravalvular aortic stenosis, dysmorphic facial features, teeth abnormalities, neurodevelopmental delay, learning disabilities, and excessively friendly personality.2 The genetic deletion that is well defined in WS is currently not considered a risk factor for cancer development.3 However, more than 15 cases of malignancy were reported in patients with WS.1,3 Here, we described a unique case of WS diagnosed with a mandibular ameloblastoma, its surgical man- agement and successful reconstruction with a vascularized fibular flap. To our knowledge, this is the first report of WS associated with ameloblastoma and first report of free flap reconstruction in a patient with WS in the literature.

From the Department of Plastic, Reconstructive and Aesthetic Surgery, Marmara University Hospital, Istanbul, Turkey. Received July 9, 2016. Accepted for publication November 2, 2016. Address correspondence and reprint requests to Fatma Betul Tuncer, MD, Marmara U¨ niversitesi Pendik EAH, Plastik, Rekonstruktif ve Estetik Cerrahi AD, 34899 Pendik, Istanbul, Turkey. E-mail: [email protected] The authors report no conflicts of interest. Copyright # 2017 by Mutaz B. Habal, MD FIGURE 1. (A) Preoperative panoramic x-ray showing the localization of the ISSN: 1049-2275 ameloblastoma in the left ramus of the mandible. (B) Postoperative panoramic DOI: 10.1097/SCS.0000000000003449 x-ray view of mandible reconstructed with fibular flap.

# 2017 Mutaz B. Habal, MD e241 Copyright © 2017 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited. Brief Clinical Studies The Journal of Craniofacial Surgery Volume 28, Number 3, May 2017 effect of elastin deficiency on free tissue transfer has not been known, the patient presented here was the first patient with WS who underwent uncomplicated free tissue transfer in the literature. A Rare Concha Variation: Another important information to keep in mind while operating on a patient with WS is the fact that 25- to 100-fold higher risk for Coronal Cleft sudden death under anesthesia exists for patients with WS due to Serap Yucel, MD, Hediye Pinar Gunbey, MD, Emre Gunbey, supravalvular aortic stenosis and other cardiac anomalies.1 MD,y Asli Tanrivermis Sayit, MD, and Kerim Aslan, MD In addition to elastin, a number of DNA repair , and several 3,6 tumor suppressor genes were mapped to the WS critical region. Abstract: Nasal turbinates are embryologically derived from a 7 One of the tumor suppressor genes located in this region is BCL7B. series of outgrowths from the foetal lateral nasal wall. These A number of studies have shown that BCL7 family is involved in outgrowths form a series of ridges, referred to as ‘‘ethmoturbinals’’ cancer initiation, progression, and development. Other oncogenesis- and have several vital functions. Several different turbinate vari- related genes on chromosome 7q11.23 are PMS 2, which plays a role in DNA repair; RFC2, which encodes a protein in the repair of UV- ations have been reported so far. The authors presented 3 patients of induced DNA damage; GTF2I, which encodes a transcription factor coronal clefted concha who were diagnosed with magnetic reson- that provides genomic instability and BAZ1B, also known as WS ance imaging. Computed tomography scans and nasal endoscopic transcription factor.3 Williams syndrome transcription factor, with its examinations are also performed subsequently. These patients are intrinsic tyrosine kinase activity, is critical for DNA repair and also, the first coronal clefted concha cases in the literature and also the regulates the sonic hedgehog pathway that was interestingly shown to first radiological study defining concha cleft. This shows paucity of 8–10 be activated in the odontogenic cysts and ameloblastoma. data documenting variations in the lateral nasal wall. Understanding It should also be noted that no increased overall risk of devel- the anatomy and the anatomic variations of the nasal cavity and oping cancer was found in people with constitutional abnormality of nasal turbinates is critical to guide the procedure due to its close , despite genetic alterations involving chromosome proximity to vital structures such as orbita and skull base, especially 7, such as deletions at 7q11 region, are frequently seen in human malignancies.4,6 for functional endoscopic sinus surgery that is a widely used The transcription map of the critical region involved in WS is technique nowadays. not yet complete. Further exploration of this region may yield new genes that are important in the process of oncogenesis. It can be Key Words: Concha cleft, concha cleft CT, concha variations speculated that the deletion of a part of chromosome 7 in WS could lead to malignant transformation through the loss of heterozygosity asal turbinates are embryologically derived from a series of in a tumor suppressor gene or dysregulation of DNA repair mech- N outgrowths from the foetal lateral nasal wall. These out- anisms. But further molecular and clinical studies are required to growths form a series of ridges, referred to as ‘‘ethmoturbinals.’’1 reveal a true linkage between WS and tumor development. In the These components of the lateral nasal wall are necessary structures future, the genetics of WS can be investigated to elicit tumorigen- for the maintenance of normal nasal functions such as humidifi- esis process and WS may be considered one of the cancer suscepti- cation, hydration, lubrication of the upper respiratory system, bility syndromes, with increasing clinical reports and case series olfaction, filtration, and thermoregulation.2,3 Several different about tumor development in WS. turbinate variations have been reported so far, most of them being in middle turbinate. These are pneumatized, lateralized, hypoplas- REFERENCES tic, agenesis, hypertrophic, paradoxically curved, secondary, accessory, L-shaped, sagittal cleft, transverse cleft, bifurcate, 1. Chonan M, Kanamori M, Kumabe T, et al. Pilomyxoid astrocytoma of 4–7 the with Williams syndrome: a case report. Childs Nerv Syst trifurcate, and septated turbinates. Pneumatized concha is the 4,8,9 2013;29:1211–1214 most common one. Only a few clefted concha patients are 2. Kandasamy S, Saxena D, Kishore Y, et al. Williams syndrome: a case described in the literature andthesearereportedtobein series. Indian Pediatr 2014;51:411–412 middle turbinates. 3. Guenat D, Quentin S, Rizzari C, et al. Constitutional and somatic Understanding the anatomy and the anatomic variations of the deletions of the Williams-Beuren syndrome critical region in non- nasal cavity and nasal turbinates is critical for guiding procedures, Hodgkin . J Hematol Oncol 2014;7:82 especially for functional endoscopic sinus surgery that is a widely 4. Montano N, De Bonis P, Lauriola L, et al. Late onset cerebellar metastasis from oesophageal adenocarcinoma in Williams Syndrome. used technique nowadays due to its close proximity to vital struc- J Neurooncol 2008;88:349–351 tures such as orbita and skull base. 5. Bank AJ, Wang H, Holte JE, et al. Contribution of collagen, elastin, and We presented 3 patients of coronal clefted that were diagnosed smooth muscle to in vivo human brachial artery wall stress and elastic with magnetic resonance (MR) or computed tomography (CT) modulus. Circulation 1996;94:3263–3270 imaging. 6. Hasle H, Olsen JH, Hansen J, et al. Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities. Cancer Genet Cytogenet 1998;105:39–42 From the Department of Radiology; and yDepartment of Otorhinolaryn- 7. Jadayel DM, Osborne LR, Coignet LJ, et al. The BCL7 gene gology Head and Neck Surgery, Faculty of Medicine, Ondokuz Mayis family: deletion of BCL7B in Williams syndrome. Gene 1998; University, Samsun, Turkey. 224:35–44 Received October 20, 2016. 8. Xiao A, Li H, Shechter D, et al. WSTF regulates the H2A X DNA Accepted for publication November 3, 2016. damage response via a novel tyrosine kinase activity. Nature Address correspondence and reprint requests to Serap Yucel, MD, Depart- 2009;457:57–62 ment of Radiology, Ondokuz Mayis University, 55139 Kurupelit, 9. Barnett C, Yazgan O, Kuo HC, et al. Williams Syndrome Transcription Samsun, Turkey; E-mail: [email protected] Factor is critical for neural crest cell function in Xenopus laevis. Mech The authors report no conflicts of interest. Dev 2012;129:324–338 Copyright # 2017 by Mutaz B. Habal, MD 10. Zhang L, Chen XM, Sun ZJ, et al. Epithelial expression of SHH ISSN: 1049-2275 signaling pathway in odontogenic tumors. Oral Oncol 2006;42:398–408 DOI: 10.1097/SCS.0000000000003451 e242 # 2017 Mutaz B. Habal, MD Copyright © 2017 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.