The Journal of Craniofacial Surgery
Brief Clinical Studies
LEOPARD Syndrome: Maxillofacial Care Ikenna Valentine Aboh, MD, PhD,* Glauco Chisci, DDS,* Paolo Gennaro, MD, PhD,* Guido Gabriele, MD,Þ Flavia Cascino, MD,Þ Alessandro Ginori, MD,þ Filippo Giovannetti, MD, PhD,Þ Giorgio Iannetti, MD, PhD*Þ Abstract: This article reports a case of a boy with LEOPARD syndrome with unusual mandibular osteolytic osteoclastic-like lesions and eruption disorder. The patient was referred to our department for bilateral facial swelling: systemic examinations, diagnosis, and dental and maxillofacial care are reported. Key Words: LEOPARD syndrome, osteolytic osteoclastic-like lesions, eruption disorder, bilateral facial swelling, maxillofacial care
L
EOPARD syndrome (LS; OMIM 151100) is a rare autosomal dominant dysmorphic syndrome characterized by the presence of skeletal and cardiac malformations associated with multiple lentigines and cafe´-au-lait spots. Recently, this condition was found part of syndromes of the RAS/MAPK pathway, which also include the Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, and other RASopathies.1 The name LEOPARD is the acronym for its major features: multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of (male) genitalia, retardation of growth, and sensorineural deafness. Diagnosis is based on genetic and molecular testing, as clinical manifestations are variable. The aim of this article was to present a case of LS with a significant involvement of mandible and teeth, and the surgical and dental care provided.
& Volume 25, Number 3, May 2014
syndrome, cherubism, or LEOPARD syndrome. At the panoramic radiographs, mandibular neoformations appeared to dislocate the molar buds. Genetic tests revealed no mutations in the NF1 gene (responsible for neurofibromatosis 1), but evidenced a t468m gene mutation in the heterozygous state in exon 12 of the PTPN11 gene, suggestive of an LS. Once the diagnosis was established, we planned for a bilateral neoformations removal with bone curettage and remodeling. No teeth were extracted. The pathological study of these neoformations underlined osteolytic lesions with numerous osteoclastic-like giant cells surrounded by fibrous stroma with spindle cells and numerous vessels (Fig. 2). The boy was hospitalized the day before surgery and was discharged after 9 days; the father and the brother were invited to perform similar investigations. At the ambulatory postoperative visits, the patient was reviewed for routine dental and orthodontic care, prophylaxis, and prevention. At the 6-month follow-up visit, the patient had a good outcome, with no presence of bilateral swelling, and was administered an orthodontic treatment (Fig. 3).
DISCUSSION LEOPARD syndrome is a systemic syndrome requiring a multidisciplinary approach: pediatricians and dentists are the first specialists who encounter such patients, often occasionally. The incidence of this syndrome is rare, but early diagnosis is crucial for prevention of specific complications of this syndrome: hypertrophic cardiomyopathy and valvular pulmonary stenosis are frequent in these patients.2 Thus, dentists must always take into account the possibility of genetic syndrome, in cases of suspected maxillomandibular malformations and teeth eruption disorders: the exclusion of supernumerary
CLINICAL REPORT AND DIFFERENTIAL DIAGNOSIS A 6-year-old Italian boy was accompanied by his parents to the Department of Oral and Maxillofacial Surgery in Siena for prolonged bilateral facial swelling and teeth eruption disorders. At the preliminary dental and maxillofacial examination, no teeth-related pathologies were found, and parents were informed of the possibility of a systemic syndrome and accepted further clinical, radiological, and laboratory examinations at our university hospital (Fig. 1). Medical history revealed cases of neuropathies among relatives; both the brother and the father presented multiple lentigines and cafe´-au-lait spots, suggestive of genetic syndrome, as neurofibromatosis 1, Noonan
From the *Department of Maxillofacial Surgery, University of Siena, Siena; †Department of Maxillofacial Surgery, BSapienza[ University of Rome, Rome; and ‡Department of Pathology, University of Siena, Siena, Italy. Received August 23, 2013. Accepted for publication November 26, 2013. Address correspondence and reprint requests to Glauco Chisci, DDS, Department of Maxillofacial Surgery, University of Siena, Policlinico BLe Scotte,[ Viale M. Bracci, 16, I-53100 Siena, Italy; E-mail: [email protected] The authors report no conflicts of interest. Copyright * 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000616
1094
FIGURE 1. Patient frontal aspect shows significant bilateral swelling (A); preoperative three-dimensional computed tomography scan shows the presence of bilateral multiple mandibular neoformations, confirmed on panoramic radiograph, dislocating lower molars (B, C).
* 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery
& Volume 25, Number 3, May 2014
Brief Clinical Studies
REFERENCES 1. Tidyman WE, Rauen KA. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev 2009;19:230Y236 2. Limongelli G, Pacileo G, Marino B, et al. Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. Am J Cardiol 2007;100:736Y741 3. Ho IC, O’Donnell D, Rodrigo C. The occurrence of supernumerary teeth with isolated, nonfamilial leopard (multiple lentigines) syndrome: report of case. Spec Care Dentist 1989;9:200Y202 4. Sheehy EC, Soneji B, Longhurst P. The dental management of a child with LEOPARD syndrome. Int J Paediatr Dent 2000;10:158Y160 5. Yam AA, Faye M, Kane A, et al. Oro-dental and craniofacial anomalies in LEOPARD syndrome. Oral Dis 2001;7:200Y202
FIGURE 2. Intraoperative removal of mandibular neoformation removal (A, B), with immunohistochemical staining: bone resorption lamellae replaced by fibrous tissue, with numerous osteoclastic-like giant cells (C, D).
teeth for dental eruption disorder is easily performed with a panoramic radiograph: however, Ho et al3 reported the occurrence of a supernumerary teeth on a patient affected by nonfamiliar LS and reported their treatment. Previously, other authors reported dental care for patients affected by LS and underlined the importance of diagnosis for complication prevention: Sheehy et al4 reported a case of LS with grossly carious primary teeth and explained his dental management under general anesthesia: these patients often suffer from mental retardation, and dental treatment under local anesthesia is notoriously improbable. Yam et al5 reported dental and craniofacial anomalies such as upper lateral incisors and canine agenesis and craniofacial underdevelopment (small head circumference). Our case was characterized by the great development of mandibular osteolytic lesions with numerous osteoclastic-like giant cells, which taken by itself could initially suggest cherubism. No previous articles described cases of management of these lesions in pediatric patients: osteoclastic-like giant cells are characteristic osteolytic lesions in LS but also in Noonan syndrome, a different condition with mutation of PTPN11 gene on the same chromosome. For this reason, genetic tests are needed for differential diagnosis. Once the syndrome was determined, with regard to dental and maxillofacial care, the early removal of these neoformations is important to remove the cause of eruption disorder and manage an orthodontic treatment. Thus, early diagnosis is essential, and pediatricians and dentists play an important role.
FIGURE 3. Patient frontal aspect shows a significant remission of bilateral facial swelling (A); panoramic radiograph after 6 months (B).
The Accuracy of Image-Guided Navigation for Maxillary Positioning in Bimaxillary Surgery Yi Sun, MSc,*Þ Heinz-Theo Luebbers, MD, DMD,þ Jimoh Olubanwo Agbaje, PhD, DMD,*§ Ivo Lambrichts, DDS, PhD,Þ Constantinus Politis, MD, PhD*Þ Abstract: The aim of our study was to evaluate the accuracy of image-guided maxillary positioning in sagittal, vertical, and mediolateral direction. Between May 2011 and July 2012, 17 patients (11 males, 6 females) underwent bimaxillary surgery with the use of intraoperative surgical navigation. During Le Fort I osteotomy, the Kolibri navigation system was used to measure movement of the maxilla at the edge of the upper central upper incisor in sagittal (buccal surface), vertical (incisor edge), and mediolateral (dental midline) direction. Six weeks after surgery, a postoperative CBCT scan was taken and registered to the preoperative cone-beam computed tomography scan to identify the actual surgical movement of the maxilla. Student 2-tailed paired t test was used to evaluate differences between the measured result from navigation system and actual surgical movement of the maxilla, which were 0.44 T 0.35 mm (P = 0.82) in the sagittal, 0.50 T 0.35 mm (P = 0.85) in the vertical, and 0.56 T 0.36 mm (P = 0.81) in the mediolateral direction. Our finding demonstrates that intraoperative computer navigation is a promising tool for measuring the surgical change of the maxilla in bimaxillary surgery. From the *Department Oral and Maxillofacial Surgery, St John’s Hospital Genk; and †Faculty of Medicine, Hasselt University, Diepenbeek, Belgium; ‡Clinic for Cranio-Maxillofacial Surgery, University Hospital of Zurich. Switzerland; and §Department Oral Health Sciences, KU Leuven & Oral and Maxillofacial Surgery, University Hospitals Leuven, Belgium. Received October 18, 2013. Accepted for publication December 2, 2013. Address correspondence and reprint requests to Constantinus Politis, MD, PhD, DDS, MHA, MM, Department of Oral and Maxillofacial Surgery, Leuven University Hospitals, Kapucijnenvoer 7, 2nd Floor, 3000 Leuven, Belgium; E-mail: [email protected] The authors report no conflicts of interest. Copyright * 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000633
* 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
1095
Brief Clinical Studies
LEOPARD Syndrome: Maxillofacial Care Ikenna Valentine Aboh, MD, PhD,* Glauco Chisci, DDS,* Paolo Gennaro, MD, PhD,* Guido Gabriele, MD,Þ Flavia Cascino, MD,Þ Alessandro Ginori, MD,þ Filippo Giovannetti, MD, PhD,Þ Giorgio Iannetti, MD, PhD*Þ Abstract: This article reports a case of a boy with LEOPARD syndrome with unusual mandibular osteolytic osteoclastic-like lesions and eruption disorder. The patient was referred to our department for bilateral facial swelling: systemic examinations, diagnosis, and dental and maxillofacial care are reported. Key Words: LEOPARD syndrome, osteolytic osteoclastic-like lesions, eruption disorder, bilateral facial swelling, maxillofacial care
L
EOPARD syndrome (LS; OMIM 151100) is a rare autosomal dominant dysmorphic syndrome characterized by the presence of skeletal and cardiac malformations associated with multiple lentigines and cafe´-au-lait spots. Recently, this condition was found part of syndromes of the RAS/MAPK pathway, which also include the Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, and other RASopathies.1 The name LEOPARD is the acronym for its major features: multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of (male) genitalia, retardation of growth, and sensorineural deafness. Diagnosis is based on genetic and molecular testing, as clinical manifestations are variable. The aim of this article was to present a case of LS with a significant involvement of mandible and teeth, and the surgical and dental care provided.
& Volume 25, Number 3, May 2014
syndrome, cherubism, or LEOPARD syndrome. At the panoramic radiographs, mandibular neoformations appeared to dislocate the molar buds. Genetic tests revealed no mutations in the NF1 gene (responsible for neurofibromatosis 1), but evidenced a t468m gene mutation in the heterozygous state in exon 12 of the PTPN11 gene, suggestive of an LS. Once the diagnosis was established, we planned for a bilateral neoformations removal with bone curettage and remodeling. No teeth were extracted. The pathological study of these neoformations underlined osteolytic lesions with numerous osteoclastic-like giant cells surrounded by fibrous stroma with spindle cells and numerous vessels (Fig. 2). The boy was hospitalized the day before surgery and was discharged after 9 days; the father and the brother were invited to perform similar investigations. At the ambulatory postoperative visits, the patient was reviewed for routine dental and orthodontic care, prophylaxis, and prevention. At the 6-month follow-up visit, the patient had a good outcome, with no presence of bilateral swelling, and was administered an orthodontic treatment (Fig. 3).
DISCUSSION LEOPARD syndrome is a systemic syndrome requiring a multidisciplinary approach: pediatricians and dentists are the first specialists who encounter such patients, often occasionally. The incidence of this syndrome is rare, but early diagnosis is crucial for prevention of specific complications of this syndrome: hypertrophic cardiomyopathy and valvular pulmonary stenosis are frequent in these patients.2 Thus, dentists must always take into account the possibility of genetic syndrome, in cases of suspected maxillomandibular malformations and teeth eruption disorders: the exclusion of supernumerary
CLINICAL REPORT AND DIFFERENTIAL DIAGNOSIS A 6-year-old Italian boy was accompanied by his parents to the Department of Oral and Maxillofacial Surgery in Siena for prolonged bilateral facial swelling and teeth eruption disorders. At the preliminary dental and maxillofacial examination, no teeth-related pathologies were found, and parents were informed of the possibility of a systemic syndrome and accepted further clinical, radiological, and laboratory examinations at our university hospital (Fig. 1). Medical history revealed cases of neuropathies among relatives; both the brother and the father presented multiple lentigines and cafe´-au-lait spots, suggestive of genetic syndrome, as neurofibromatosis 1, Noonan
From the *Department of Maxillofacial Surgery, University of Siena, Siena; †Department of Maxillofacial Surgery, BSapienza[ University of Rome, Rome; and ‡Department of Pathology, University of Siena, Siena, Italy. Received August 23, 2013. Accepted for publication November 26, 2013. Address correspondence and reprint requests to Glauco Chisci, DDS, Department of Maxillofacial Surgery, University of Siena, Policlinico BLe Scotte,[ Viale M. Bracci, 16, I-53100 Siena, Italy; E-mail: [email protected] The authors report no conflicts of interest. Copyright * 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000616
1094
FIGURE 1. Patient frontal aspect shows significant bilateral swelling (A); preoperative three-dimensional computed tomography scan shows the presence of bilateral multiple mandibular neoformations, confirmed on panoramic radiograph, dislocating lower molars (B, C).
* 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery
& Volume 25, Number 3, May 2014
Brief Clinical Studies
REFERENCES 1. Tidyman WE, Rauen KA. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev 2009;19:230Y236 2. Limongelli G, Pacileo G, Marino B, et al. Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. Am J Cardiol 2007;100:736Y741 3. Ho IC, O’Donnell D, Rodrigo C. The occurrence of supernumerary teeth with isolated, nonfamilial leopard (multiple lentigines) syndrome: report of case. Spec Care Dentist 1989;9:200Y202 4. Sheehy EC, Soneji B, Longhurst P. The dental management of a child with LEOPARD syndrome. Int J Paediatr Dent 2000;10:158Y160 5. Yam AA, Faye M, Kane A, et al. Oro-dental and craniofacial anomalies in LEOPARD syndrome. Oral Dis 2001;7:200Y202
FIGURE 2. Intraoperative removal of mandibular neoformation removal (A, B), with immunohistochemical staining: bone resorption lamellae replaced by fibrous tissue, with numerous osteoclastic-like giant cells (C, D).
teeth for dental eruption disorder is easily performed with a panoramic radiograph: however, Ho et al3 reported the occurrence of a supernumerary teeth on a patient affected by nonfamiliar LS and reported their treatment. Previously, other authors reported dental care for patients affected by LS and underlined the importance of diagnosis for complication prevention: Sheehy et al4 reported a case of LS with grossly carious primary teeth and explained his dental management under general anesthesia: these patients often suffer from mental retardation, and dental treatment under local anesthesia is notoriously improbable. Yam et al5 reported dental and craniofacial anomalies such as upper lateral incisors and canine agenesis and craniofacial underdevelopment (small head circumference). Our case was characterized by the great development of mandibular osteolytic lesions with numerous osteoclastic-like giant cells, which taken by itself could initially suggest cherubism. No previous articles described cases of management of these lesions in pediatric patients: osteoclastic-like giant cells are characteristic osteolytic lesions in LS but also in Noonan syndrome, a different condition with mutation of PTPN11 gene on the same chromosome. For this reason, genetic tests are needed for differential diagnosis. Once the syndrome was determined, with regard to dental and maxillofacial care, the early removal of these neoformations is important to remove the cause of eruption disorder and manage an orthodontic treatment. Thus, early diagnosis is essential, and pediatricians and dentists play an important role.
FIGURE 3. Patient frontal aspect shows a significant remission of bilateral facial swelling (A); panoramic radiograph after 6 months (B).
The Accuracy of Image-Guided Navigation for Maxillary Positioning in Bimaxillary Surgery Yi Sun, MSc,*Þ Heinz-Theo Luebbers, MD, DMD,þ Jimoh Olubanwo Agbaje, PhD, DMD,*§ Ivo Lambrichts, DDS, PhD,Þ Constantinus Politis, MD, PhD*Þ Abstract: The aim of our study was to evaluate the accuracy of image-guided maxillary positioning in sagittal, vertical, and mediolateral direction. Between May 2011 and July 2012, 17 patients (11 males, 6 females) underwent bimaxillary surgery with the use of intraoperative surgical navigation. During Le Fort I osteotomy, the Kolibri navigation system was used to measure movement of the maxilla at the edge of the upper central upper incisor in sagittal (buccal surface), vertical (incisor edge), and mediolateral (dental midline) direction. Six weeks after surgery, a postoperative CBCT scan was taken and registered to the preoperative cone-beam computed tomography scan to identify the actual surgical movement of the maxilla. Student 2-tailed paired t test was used to evaluate differences between the measured result from navigation system and actual surgical movement of the maxilla, which were 0.44 T 0.35 mm (P = 0.82) in the sagittal, 0.50 T 0.35 mm (P = 0.85) in the vertical, and 0.56 T 0.36 mm (P = 0.81) in the mediolateral direction. Our finding demonstrates that intraoperative computer navigation is a promising tool for measuring the surgical change of the maxilla in bimaxillary surgery. From the *Department Oral and Maxillofacial Surgery, St John’s Hospital Genk; and †Faculty of Medicine, Hasselt University, Diepenbeek, Belgium; ‡Clinic for Cranio-Maxillofacial Surgery, University Hospital of Zurich. Switzerland; and §Department Oral Health Sciences, KU Leuven & Oral and Maxillofacial Surgery, University Hospitals Leuven, Belgium. Received October 18, 2013. Accepted for publication December 2, 2013. Address correspondence and reprint requests to Constantinus Politis, MD, PhD, DDS, MHA, MM, Department of Oral and Maxillofacial Surgery, Leuven University Hospitals, Kapucijnenvoer 7, 2nd Floor, 3000 Leuven, Belgium; E-mail: [email protected] The authors report no conflicts of interest. Copyright * 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000633
* 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
1095
