Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis.

Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.

A rare case of Gardner syndrome in an African adult male: A case report.

Gardner's syndrome with the complete manifestation of colonic and extracolonic features is uncommon. Therefore, every clinician should view extracolonic features with a high index of suspicion. This may be key to early diagnosis, definitive management in these patients and importantly, helps prevent malignant transformation of existing colonic polyps.

Surgical Proposition of a Slow-Growing Calvarial Exostosis in a Female Patient With a Congenital Iris Cyst of the Anterior Chamber and Mandibular Tori.

We present an unusual case of a woman in her early 50s with a slow-growing calvarial exostosis. Exostoses are bony spurs or osteomas extending outward beyond a bone's surface and may be benign or malignant. Calvarial exostoses are a less common bone tumor that can occur in the population. We present a case of a rare, slow-growing calvarial exostosis with a combination of mandibular tori and a congenital iris cyst. We discuss differentials of this exostosis and different syndromes that may cause it such as hereditary multiple exostoses and Gardner syndrome. The current article aims to spread awareness of this atypical presentation of exostoses and present our institution's surgical proposition for removing a calvarial exostosis to obtain a further histological analysis of its composition. As these masses may commonly be benign, a definitive diagnosis cannot be made through imaging alone to rule out more threatening conditions. We have addressed radiological findings and diagnostic and treatment options offered to the patient. The patient decided not to move forward with removing the mass and would continue to monitor and return should she notice any unusual or acute changes.

Diagnostic implications of Gardner Syndrome, case report of a familial adenomatous polyposis (FAP) variant, for eye care professionals.

INTRODUCTION: Gardner Syndrome (GS) is a variant of Familial Adenomatous Polyposis (FAP). FAP is characterized by several precancerous adenomatous intestinal polyps while GS has additional distinct extraintestinal features such as congenital hypertrophy of retinal epithelium (CHRPE), which we describe here. PRESENTATION OF CASE: 42-year-old male with GS presenting with flashes and floaters observed to have CHRPE-like lesions characteristic of GS. DISCUSSION: Subtle CHRPE findings differentiate pathological, described in the present case, from non-pathological etiologies and may guide further management. CONCLUSION: Here we present the signs and symptoms that raise suspicion for GS associated with CHRPE and how to approach management late in the disease presentation.

Long-term follow-up of torpedo maculopathy: a case series and mini-review.

BACKGROUND: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition. CASE REPORTS: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected. CONCLUSIONS: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome.

A novel APC mutation associated with Gardner syndrome in a Chinese family.

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

A role for total alloplastic temporomandibular joint replacement in Gardner syndrome.

Gardner syndrome (GS) is a rare autosomal dominant disorder that can present with craniomaxillofacial abnormalities. The identification of osteomas or craniomaxillofacial abnormalities can therefore serve as a marker of this condition, facilitating early referral and diagnosis. A 17-year-old female with GS was referred for the management of severe limited mouth opening, causing a major problem for routine endoscopy to monitor the gastrointestinal alterations of GS. Clinical and radiological evaluations showed multiple osteomas in the mandibular angle, condylar and coronoid regions bilaterally and maximum mouth opening of 8 mm. The patient underwent surgery for osteoma removal and bilateral customized alloplastic total temporomandibular joint replacement (TMJ-TJR). At the 2-year follow-up, the patient showed improvements in quality of life, with a maximum mouth opening of 34 mm, allowing routine upper endoscopy to be performed. This is the first report of GS, a rare and challenging craniomaxillofacial abnormality, treated with TMJ-TJR. A comprehensive overview of the patient's clinical presentation, diagnostic assessment, treatment planning, and outcomes is provided.

Papillary thyroid carcinoma with desmoid fibromatosis: a case report and review of literature.

Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by an unpredictable and variable clinical course. We present the case of a 56-year-old woman who underwent total thyroidectomy for papillary thyroid carcinoma in 2012 and who developed a cervical mass at the left laterocervical level during follow-up, raising the diagnosis of tumor recurrence. Computed tomography of the neck showed solid formations with heterogeneous contrast uptake in the right lateral region of the neck. At the level of the thoracic operculum, a second 26-mm formation was observed that medially contacted the left lateral wall of the trachea. Lateral lymphadenectomy was performed, which was incomplete. Histology showed findings consistent with desmoid-type fibromatosis. DF are slowly proliferating, non-metastatic tumors with a highly invasive capacity that are usually present in familial adenomatous polyposis (FAP)-Gardner syndrome. Our case had a history of massive colonic polyposis and first-degree relatives of colorectal cancer.

La fibromatosis de tipo desmoide (FD) es una rara proliferación fibroblástica monoclonal caracterizada por un curso clínico impredecible y variable. Presentamos el caso de una mujer de 56 años intervenida de tiroidectomía total por carcinoma papilar de tiroides en 2012 y que durante el seguimiento desarrolla una masa cervical a nivel laterocervical izquierdo, planteando el diagnóstico de recidiva tumoral. La tomografía computarizada de cuello demostró formaciones sólidas con captación heterogénea de contraste en la región lateral derecha del cuello. A nivel del opérculo torácico se observó una segunda formación de 26 mm que contactaba medialmente con la pared lateral izquierda de la tráquea. Se realizó una linfadenectomía lateral, que resultó incompleta. La histología mostró hallazgos compatibles con FD. La FD son tumores de proliferación lenta, no metastásicos y con una capacidad altamente invasiva que suelen estar presentes en la poliposis adenomatosa familiar (PAF)-síndrome de Gardner. Nuestro caso tenía antecedentes de poliposis colónica masiva y familiares de primer grado de cáncer colorrectal.

Extracolonic manifestations of Gardner syndrome: A case report.

Gardner syndrome has head and neck manifestations that may be recognized during dental visits. Features such as multiple gnathic osteomas, impacted supernumerary teeth, and multiple foci of idiopathic osteosclerosis can be easily identified on dental radiographs, prompting the clinician to refer the patient for further investigation. A dental examination and routine radiographs play a vital role in revealing the extracolonic presentation of Gardner syndrome, which facilitates timely screening and detection of colorectal cancer and other malignancies associated with this condition. This report discusses the case of a 50-year-old Caucasian man who presented with a hard swelling of the left angle of the mandible and was diagnosed with Gardner syndrome based on abnormal findings from an oral examination, dental imaging, and medical and family history.

Multiple Gardner Syndrome Osteomas Mimicking Temporomandibular Ankylosis: Case Report.

Objectives: This study aims to report a delayed Gardner syndrome diagnosis mimicking temporomandibular ankylosis. Methods: An 11-year-old patient was treated at the Hospital Josina Machel, Luanda, Angola for severe chronic trismus without TMJ involvement. Some difficulties in diagnosis and final results were discussed. Case report: A delayed diagnosis of Gardner syndrome was treated by the authors. The delay was due to a lack of timely CT scans and some COVID-19 pandemic restrictions. This delay worsened the patient´s clinical condition for several months. Classic surgical gap arthroplasty has been used and considered successful, particularly when material is scarce. Conclusions: Classical surgical techniques are still very useful in some parts of the world that do not rely on modern technology. International collaboration through teledentistry, case review over the Internet, and humanitarian or educational missions are very helpful in low-income countries.

Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth.

The activation of Wnt/ß-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3ß-APC ß-catenin destruction complex, functions to modulate Wnt/ß-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT/ß-catenin signalling and subsequent familial adenomatous polyposis (FAP; MIM 175100) with or without multiple supernumerary teeth. The ablation of Apc function in mice also results in the constitutive activation of ß-catenin in embryonic mouse epithelium and causes supernumerary tooth formation. The objective of this study was to investigate if genetic variants in the APC gene were associated with supernumerary tooth phenotypes. We clinically, radiographically, and molecularly investigated 120 Thai patients with mesiodentes or isolated supernumerary teeth. Whole exome and Sanger sequencing identified three extremely rare heterozygous variants (c.3374T>C, p.Val1125Ala; c.6127A>G, p.Ile2043Val; and c.8383G>A, p.Ala2795Thr) in APC in four patients with mesiodentes or a supernumerary premolar. An additional patient with mesiodens was compound as heterozygous for two APC variants (c.2740T>G, p.Cys914Gly, and c.5722A>T, p.Asn1908Tyr). Rare variants in APC in our patients are likely to contribute to isolated supernumerary dental phenotypes including isolated mesiodens and an isolated supernumerary tooth.

Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review.

Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.

Orbital osteomas associated with Gardner's syndrome: a case presentation and review of literature.

Gardner syndrome (GS) is a rare genetic disorder characterized by numerous intestinal colon polyps with various extraintestinal manifestations. Osteomas are a known extracolonic manifestation of GS and can affect the orbit, as seen in our patient, as well as 13 other cases documented in literature. Excision of large orbital osteomas can be successful with a multi-disciplinary approach as presented in this article. Ophthalmologists can even be the first to diagnose GS, usually via the presence of congenital hypertrophy of the retinal pigment epithelium (CHRPE) lesions. Untreated, 100% of colon polyps will transform into cancer, thus it is important to be aware of this rare syndrome with ophthalmic manifestations and screen patients with osteomas for GS.

Gardner's syndrome: Simultaneous diagnosis and treatment in monozygotic twins.

Gardner's syndrome (GS) is a very rare autosomal dominant multisystem disease. Osteomas, skin and soft tissue tumors are present with gastrointestinal polyposis. The polyps have very high malignancy potentials. If prophylactic resection is not performed, colorectal cancer development is inevitable in all patients with GS. Polyposis is usually asymptomatic. Therefore, careful evaluation of extraintestinal findings of the disease is very important for early diagnosis. In this article, diagnosis and treatment of GS are presented in monozygotic twins, which have not been previously described in the literature. The diagnostic process, which started with dental complaints of one case, was carried out in an effective manner and then, prophylactic surgery was performed in twins. This article aimed to make clinicians and dentists attentive for early diagnosis of disease and to review treatment options.

Giant Osteoma of the Mandible: Report of a Rare Case with Review of Literature.

Osteoma is a slow growing, asymptomatic, benign bony tumor composed of compact and cancellous bones. Central, peripheral, and extra skeletal osteomas are the three types based on the site of origin. They are mostly observed on routine radiographic screening, mostly in the paranasal sinuses. Gnathic involvement is an uncommon occurrence, and if present, mandibular involvement is more frequently seen. Mostly, osteomas are small asymptomatic lesions and very rarely they become symptomatic and acquire larger size. Multiple osteomas are a feature of Gardner's syndrome; however, solitary osteomas are non-syndromic. Oral health professional may be the first to diagnose Gardner's syndrome as the osteomas may be initial manifestation of the disorder. Treatment protocol of osteomas varies based on the associated signs and symptoms. Small, asymptomatic cases are treated conservatively by periodic clinical and radiographic evaluation. However, larger, symptomatic lesions require surgical intervention. Herby, reporting an unusual case of Giant peripheral osteoma of the mandible. Our case is unique in few aspects because of its unusually large size (5 × 4 cm) and involvement of lingual aspect of the mandible in the region of sublingual fossa, with compression of the floor of mouth.

Percutaneous ultrasound-guided radiofrequency ablation for giant desmoid tumors of the intra-abdominal cavity in a patient with Gardner syndrome.

Gardner syndrome (GS) is a rare variant of familial adenomatous polyposis, leading to numerous intra- and extracolonic lesions. Extracolonic lesions of GS are most common with desmoid tumors (DTs) in the abdominal wall, intra-abdominal cavity, and mesentery. Surgery remains the primary treatment for DTs; however, the patients are challenged with the high recurrence rate after surgical resection, and wide resection often results in debilitating loss of function. This study presents a case of a 47-year-old female with GS who had undergone total colectomy and ultra-low anastomosis of the ileal anal canal, and she developed giant DTs in the intra-abdominal cavity. The patient underwent ultrasound-guided percutaneous radiofrequency ablation (RFA) for intra-abdominal DTs in September 2014, October 2015, and January 2016. Palliative RFA significantly slowed the progression of the tumor and improved the symptoms of abdominal compression; thus, it is a possible therapeutic option for intra-abdominal unresectable DTs in patients with GS.

Tumor desmoide abdominal gigante en puerperio: caso clínico y revisión de la literatura / Giant abdominal desmoid tumor during the puerperium: Case report and review of literature

Introducción. Los tumores desmoides o fibromatosis agresiva corresponden a neoplasias mesenquimales poco frecuentes. Son tumores localmente agresivos que ocurren especialmente en jóvenes, no desarrollan metástasis a distancia, pero se asocian con invasión locorregional y alta tasa de recurrencia después de la resección. Su etiología es desconocida, pero se ha asociado al síndrome de Gardner, trauma, embarazo, estados hiperestrogénicos y puerperio. El objetivo de este artículo fue hacer una revisión sobre el tema a propósito de un caso clínico. Caso clínico. Se presenta el caso de una paciente puérpera con progresivo y rápido aumento del volumen abdominal. Se realizó una tomografía computarizada de abdomen y pelvis que confirmó la presencia de una masa intraperitoneal bien definida. La paciente fue operada con escisión de la masa y confirmación histológica de tumor desmoide a partir de la muestra de patología. Discusión. Los tumores desmoides tienen una incidencia de 2 a 4 casos por millón de habitantes por año, con leve predominio en el sexo femenino y representan menos del 3 % de los tumores de partes blandas. Aunque el tumor se puede ubicar a nivel intraabdominal o en la pared, la ubicación más común es en las extremidades. Conclusiones. La sospecha y detección del tumor desmoide es fundamental, así como su adecuado estudio, para determinar el tratamiento quirúrgico como fue realizado en este caso

Introduction. Desmoid tumors or aggressive fibromatosis correspond to rare mesenchymal neoplasms. They are locally aggressive tumors that occur especially in young people, they do not develop distant metastases, but are associated with locoregional invasion and a high recurrence rate after resection. Its etiology is unknown, but it has been associated with Gardner syndrome, trauma, pregnancy, hyperestrogenic states, and puerperium. The objective of this article was to review the topic based on a clinical case. Clinical case. The case of a puerperal patient with progressive and rapid increase in abdominal volume is presented. An abdominal and pelvic CT scan was performed, which confirmed the presence of a well-defined intraperitoneal mass. The patient underwent surgery with excision of the mass and histological confirmation of a desmoid tumor from the pathology sample. Discussion. Desmoid tumors have an incidence of 2 to 4 cases per million inhabitants per year, with a slight predominance in females, and represent less than 3% of soft tissue tumors. Although the tumor can be located intra-abdominal or in the wall, the most common location is in the extremities. Conclusions. The suspicion and detection of the desmoid tumor is essential, as well as its adequate study to determine the surgical treatment as it was done in this case

Phenotypic dento-osseous characterization of a Brazilian family with Familial Adenomatous Polyposis.

OBJECTIVE: To perform a phenotypic characterization of the dento-osseous anomalies in a Brazilian family with Familial Adenomatous Polyposis (FAP) and to investigate the adenomatous polyposis coli (APC) causative variant. DESIGN: The study included a family of 14 individuals (Group A: affected; Group B: non-affected). The frequency of radiographic findings in both groups was evaluated according to the Dental Panoramic Radiograph Score (DPRS) diagnostic method. The accuracy and reproducibility of DPRS were tested. The DNA was isolated from the index patient's saliva and submitted to whole-exome and Sanger sequencing approach. RESULTS: DPRS ≥ 7 was observed in 80 % of Group A but in none of Group B. The most common findings in Group A were dense bone islands (60 %), hazy sclerosis (40 %), osteomas (40 %), and supernumerary tooth (20 %). DPRS has proved to be a reliable method while DPRS ≥ 5 and DPRS ≥ 7 were taken as positive for FAP, and reproducible diagnosis test considering that the evaluators correctly identified the affected patients (Kappa agreement>0.8, p = 0.002). A nonsense heterozygous mutation in the APC gene (c.1370C > G; p.Ser457*) of the index case was detected. CONCLUSION: FAP patients have a higher frequency of dento-osseous anomalies (p = 0.005). Bone abnormalities were more prevalent than dental anomalies (p = 0.001). Thus, FAP patients should be referred for dental examination and genetic counseling to perform early diagnosis of dento-osseous anomalies and evaluate the implications of the molecular findings in each particular family.

Gardner syndrome with odontogenic sinusitis: A case report.

Gardner syndrome with odontogenic sinusitis is rare but should be suspected in patients with multiple osteomas of the skull and facial bones, excess teeth, impacted teeth, and odontomas. Early diagnosis and treatment of GS may improve prognosis.

Torpedo-like lesions in the ocular fundi of Gardner syndrome: hiding in plain view.

Background: The coexistence of fundus torpedoes and Gardner syndrome was initially reported in 1989 and 1992 by Gass and Roseman. Gardner syndrome is a dominantly inherited disease characterized by a multitude of potentially lethal gastrointestinal polyps. Over the ensuing quarter century, several publications demonstrated uncommon, but easily recognized, fundus lesions called Torpedo Maculopathy in apparently normal individuals. These fundus abnormalities were thought to be single and isolated without systemic associations. During the same period of time, a variety of nonspecific fundus abnormalities were described in Gardner syndrome, which, in retrospect, included highly specific lesions that closely resembled macular torpedoes and sometimes were indistinguishable from them.Patient and methods: We now report a confirmed case of Gardner syndrome with numerous fundus torpedoes, and carefully analyze the voluminous literature of both Gardner syndrome and Torpedo Maculopathy.Results: We demonstrate shared features of the fundus lesions in both diseases, and hypothesize that they may have genetic as well as ophthalmoscopic similarities in common.Conclusions: We therefore recommend that individuals with classic isolated torpedoes undergo evaluations for mutations in the Gardner gene (Adenomatous polyposis coli) and for the presence of gastrointestinal polyps and other systemic features of Gardner syndrome. We also suggest that apparently normal individuals, who are genetically related to patients with known classic torpedoes, undergo inspection of their fundi for the possible presence of characteristic lesions.