AUTHOR=Antal Gréta , Zsigmond Anna , Till Ágnes , Orsi Eniko , Szanto Ildiko , Büki Gergely , Kereskai László , Herbert Zsuzsanna , Hadzsiev Kinga , Bene Judit 

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

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 30 - 2024

YEAR=2024

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2024.1611768

DOI=10.3389/pore.2024.1611768

ISSN=1532-2807

ABSTRACT=Gardner syndrome is a rare genetic cancer predisposition disorder characterised by intestinal polyposis, multiple osteomas, and soft and hard tissue tumours. Dental anomalies are present in around 30% to 70% of patients with Gardner syndrome and can be discovered during routine dental examination. 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 ultimate diagnosis was established with the help of comprehensive genetic analysis based on state-of-the-art next generation sequencing technology.A 17 year-old female index patient had dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembled to Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to atypical bone abnormality identified by panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolism disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbal subcutaneous tumor was discovered by physical examination.Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her 2 years younger sister at her age of 14 had some benign tumors: (multiple exostosis, odontomes, epidermoid cysts) and impacted teeth. Their mother had skeletal symptoms as well. Her lower teeth did not develop, the 9th-10th ribs were fused, she complains of intermittent jaw pain. 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 detected the same variant in the sister's and the mother's DNA. 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 the patients to genetic counselling. The 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.