Identification of inflammatory response-related molecular mechanisms based on the ATM/ATR/p53 pathway in tumor cells.

Inflammatory response is a crucial factor that affects prognosis and therapeutic effect in tumor cells. Although some studies have shown that inflammation could make DNA more vulnerable to external attacks, resulting in serious DNA damage, the underlying mechanism remains unknown. Then, using tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS), this research elevated the level of inflammation in cancer cells, and hydrogen peroxide (H2O2) and ultraviolet (UV) were utilized as common reactive oxygen species (ROS)-induced DNA damage agents. We show that either H2O2 or UV achieved a more substantial antiproliferative effect in the inflammation environment compared with H2O2 or UV treatment alone. The inflammation environment enhanced H2O2- or UV-induced cell apoptosis and ROS production. Although the phenomenon that inflammation itself could trigger ROS-dependent DNA damage was well known, the underlying mechanism for the sensitization of inflammation to trigger intense DNA damage via ROS in cancer cells remains unclear. In this study, the inflammation-related genes and the corresponding expression information were obtained from the TCGA and fetched genes associated with inflammatory factors. Screening of thirteen inflammatory-related, including ATM, and prognostic genes. In addition, KEGG analysis of prognostic genes shows that biological processes such as DNA replication. ATM and ATR, which belong to the PI3/PI4-kinase family, can activate p53. Inflammation promotes the vulnerability of DNA by activating the ATM/ATR/p53 pathway, while not affecting the DNA damage repair pathway. In brief, this research suggested that inflammation made DNA vulnerable due to the amplifying H2O2- or UV-induced ROS production and the motoring ATM/ATR/p53 pathway. In addition, our findings revealed that inflammation's motoring of the ATM/ATR/p53 pathway plays a crucial role in DNA damage. Therefore, exploring the mechanism between inflammation and ROS-dependent DNA damage would be extremely valuable and innovative. This study would somewhat establish a better understanding of inflammation, DNA damage, and cancer.

SPIN1 facilitates chemoresistance and HR repair by promoting Tip60 binding to H3K9me3.

The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.

Clinical and genetic spectrum of Ataxia Telangiectasia Tunisian patients: Bioinformatic analysis unveil mechanisms of ATM variants pathogenicity.

Ataxia Telangiectasia (AT) is a rare multisystemic neurodegenerative disease caused by biallelic mutations in the ATM gene. Few clinical studies on AT disease have been conducted in Tunisia, however, the mutational landscape is still undefined. Our aim is to determine the clinical and genetic spectrum of AT Tunisian patients and to explore the potential underlying mechanism of variant pathogenicity. Sanger sequencing was performed for nine AT patients. A comprehensive computational analysis was conducted to evaluate the possible pathogenic effect of ATM identified variants. Genetic screening of ATM gene has identified nine different variants from which six have not been previously reported. In silico analysis have predicted a pathogenic effect of identified mutations. This was corroborated by a structural bioinformatics study based on molecular modeling and docking for novel missense mutations. Our findings suggest a profound impact of identified mutations not only on the ATM protein stability, but also on the ATM-ligand interactions. Our study characterizes the mutational landscape of AT Tunisian patients which will allow to set up genetic counseling and prenatal diagnosis for families at risk and expand the spectrum of ATM variants worldwide. Furthermore, understanding the mechanism that underpin variant pathogenicity could provide further insights into disease pathogenesis.

Targeting the ATM pathway in cancer: Opportunities, challenges and personalized therapeutic strategies.

Ataxia telangiectasia mutated (ATM) kinase plays a pivotal role in orchestrating the DNA damage response, maintaining genomic stability, and regulating various cellular processes. This review provides a comprehensive analysis of ATM's structure, activation mechanisms, and various functions in cancer development, progression, and treatment. I discuss ATM's dual nature as both a tumor suppressor and potential promoter of cancer cell survival in certain contexts. The article explores the complex signaling pathways mediated by ATM, its interactions with other DNA repair mechanisms, and its influence on cell cycle checkpoints, apoptosis, and metabolism. I examine the clinical implications of ATM alterations, including their impact on cancer predisposition, prognosis, and treatment response. The review highlights recent advances in ATM-targeted therapies, discussing ongoing clinical trials of ATM inhibitors and their potential in combination with other treatment modalities. I also address the challenges in developing effective biomarkers for ATM activity and patient selection strategies for personalized cancer therapy. Finally, I outline future research directions, emphasizing the need for refined biomarker development, optimized combination therapies, and strategies to overcome potential resistance mechanisms. This comprehensive overview underscores the critical importance of ATM in cancer biology and its emerging potential as a therapeutic target in precision oncology.

SNRPB promotes osteosarcoma progression via activating ATM signaling pathway through RRM2.

Osteosarcoma is a malignant bone tumor characterized by high metastatic potential and recurrence rates post-therapy. The small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB), a core component of spliceosome, have been reported to exhibit upregulation across several cancer types. However, the precise role of SNRPB in osteosarcoma progression remains poorly elucidated. Herein, we explored SNRPB expression in human osteosarcoma tissues and normal bone tissues by immunohistochemical staining (IHC) staining, revealing a notable upregulation of SNRPB in osteosarcoma, correlating with diminished survival rates. Moreover, the in vitro loss-of-function experiments showed that SNRPB knockdown significantly suppressed the osteosarcoma cell proliferation and migration, as well as tubule formation of HUVECs, while enhancing osteosarcoma cell apoptosis. Mechanistically, we revealed that SNRPB promoted the transcription of ribonucleotide reductase subunit M2 (RRM2) via E2F transcription factor 1 (E2F1). Further rescue experiments indicated that RRM2 was required for SNRPB-induced malignant behaviors in osteosarcoma. Additionally, we confirmed that the function of SNRPB in osteosarcoma cell growth and apoptosis was associated with ATM signaling pathway activation. In conclusion, our findings provide initial insights into the underlying mechanisms governing SNRPB-induced osteosarcoma progression and proposed for SNRPB as a novel therapeutic target in osteosarcoma management.

Hematopoietic stem/progenitor cell transplantation recovers immune defects and prevents lymphomas in Atm-deficient mice.

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal recessive multi-system and life-shortening disease, characterized by progressive cerebellar neurodegeneration, immunodeficiency, radiation sensitivity and cancer predisposition, with high incidence of leukemia and lymphoma. A-T is caused by mutations in the gene encoding for ATM protein that has a major role in maintaining the integrity of the genome. Because there are no cures for A-T, we aimed to tackle immunodeficiency and prevent cancer onset/progression by transplantation therapy. METHODS: Enriched hematopoietic stem/progenitor cells (HSPCs), collected from bone marrow of wild-type mice, were transplanted in the caudal vein of 1 month old conditioned Atm-/- mice. RESULTS: Genomic analyses showed that transplanted Atm positive cells were found in lymphoid organs. B cells isolated from spleen of transplanted mice were able to undergo class switching recombination. Thymocytes were capable to correctly differentiate and consequently an increase of helper T cells and TCRßhi expressing cells was observed. Protein analysis of isolated T and B cells from transplanted mice, revealed that they expressed Atm and responded to DNA damage by initiating an Atm-dependent phosphorylation cascade. Indeed, aberrant metaphases were reduced in transplanted Atm-deficient mice. Six months after transplantation, Atm-/- mice showed signs of aging, but they maintained the rescue of T cells maturation, showed DNA damage response, and prevented thymoma. CONCLUSION: We can conclude that wild-type enriched HSPCs transplantation into young Atm-deficient mice can ameliorate A-T hematopoietic phenotypes and prevent tumor of hematopoietic origin.

Whole genome joint analysis reveals ATM:C.1564_1565del variant segregating with Ataxia-Telangiectasia and breast cancer.

ATM gene is implicated in the development of breast cancer in the heterozygous state, and Ataxia-telangiectasia (A-T) in a homozygous or compound heterozygous state. Ataxia-telangiectasia (A-T) is a rare cerebellar ataxia syndrome presenting with progressive neurologic impairment, telangiectasia, and an increased risk of leukemia and lymphoma. Although the role of ATM, separately, in association with A-T and breast cancer is well documented, there is a limited number of studies investigating ATM variants when segregating with both phenotypes in the same family. Here, using joint analysis and whole genome sequencing, we investigated ATM c.1564_1565del in a family with one homozygous member presenting with A-T (OMIM # 208900) and three heterozygous members, of whom one had breast cancer (OMIM #114480). To our knowledge, this is the first study of ATM c.1564_1565del segregation with both A-T and breast cancer phenotypes within the same kindred. This study highlights the need for a comprehensive genomic approach in the appropriate cancer risk management of heterozygote carriers of ATM in families with A-T.

Identification of the main barriers to Ku accumulation in chromatin.

Repair of DNA double-strand breaks by the non-homologous end-joining pathway is initiated by the binding of Ku to DNA ends. Multiple Ku proteins load onto linear DNAs in vitro. However, in cells, Ku loading is limited to ∼1-2 molecules per DNA end. The mechanisms enforcing this limit are currently unclear. Here, we show that the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), but not its protein kinase activity, is required to prevent excessive Ku entry into chromatin. Ku accumulation is further restricted by two mechanisms: a neddylation/FBXL12-dependent process that actively removes loaded Ku molecules throughout the cell cycle and a CtIP/ATM-dependent mechanism that operates in S phase. Finally, we demonstrate that the misregulation of Ku loading leads to impaired transcription in the vicinity of DNA ends. Together, our data shed light on the multiple mechanisms operating to prevent Ku from invading chromatin and interfering with other DNA transactions.

Inhibitors of APE1 redox and ATM synergistically sensitize osteosarcoma cells to ionizing radiation by inducing ferroptosis.

The resistance of osteosarcoma (OS) to ionizing radiation (IR) is an obstacle for effective patient treatment. Apurinic/apyrimidinic endonuclease-reduction/oxidation factor 1 (APE1/Ref-1) is a multifunctional protein with DNA repair and reduction/oxidation (redox) activities. We previously revealed the role of APE1 in OS radioresistance; however, whether the redox activity of APE1 is involved in OS radioresistance is unclear. APE1 regulates the activation of ataxia-telangiectasia mutated (ATM), an initiator of DNA damage response that mediates radioresistance in other cancers. The role of APE1 redox activity and ATM activation in OS radioresistance is unknown. Our study revealed that IR increased APE1 expression and ATM activation in OS cells, and APE1 directly regulated ATM activation by its redox activity. The combined use of an APE1 redox inhibitor and ATM inhibitor effectively sensitized OS cells to IR in vitro and in vivo. Mechanistically, the increased radiosensitization of OS cells by the combined use of the two inhibitors was mediated by increased ferroptosis. Co-treatment with the two inhibitors significantly decreased expression of the common targeted transcription factor P53 compared with single inhibitor treatment. Collectively, APE1 redox activity, ATM activation and their crosstalk play important roles in the resistance of OS to irradiation. Synergetic inhibition of APE1 redox activity and ATM activation sensitized OS cells to IR by inducing ferroptosis, which provides a promising strategy for OS radiotherapy.

ATM facilitates autophagy and protects against oxidative stress and apoptosis in response to ER stress in vitro.

The endoplasmic reticulum (ER) responds to cellular stress by initiating an unfolded protein response (UPR) that mitigates misfolded protein accumulation by promoting protein degradation pathways. Chronic ER stress leads to UPR-mediated apoptosis and is a common underlying feature of various diseases, highlighting the modulators of the UPR as attractive targets for therapeutic intervention. Ataxia-telangiectasia mutated protein kinase (ATM) is a stress-responsive kinase that initiates autophagy in response to reactive oxygen species (ROS), and ATM deficiency is associated with increased ER stress markers in vitro. However, whether ATM participates in the UPR remains unclear. In this in vitro study, a novel role for ATM in the ER stress response is described using the well-characterized HEK293 cells treated with the common ER stress-inducing agent, tunicamycin, with and without the potent ATM inhibitor, KU-60019. We show for the first time that ATM is activated in a time-dependent manner downstream of UPR initiation in response to tunicamycin treatment. Furthermore, we demonstrate that ATM is required for p62-bound protein cargo degradation through the autophagy pathway in response to ER stress. Lastly, our data suggest a protective role for ATM in ER stress-mediated oxidative stress and mitochondrial apoptosis. Taken together, we highlight ATM as a potential novel drug target in ER stress-related diseases.

Multilocus inherited neoplasia allele syndrome: report of uncommon combinations between CHEK2/ATM and BRCA1/CDKN2A genes.

Background: Multilocus inherited neoplasia allelic syndrome (MINAS) is a recently coined term that describes the coexistence of two or more pathogenic variants (PVs) in cancer susceptibility genes (CSGs) in a single individual. Case presentation: This article presents two cases of MINAS due to rare CSG combinations. The first was a 37-year-old woman carrying PVs in the mutated ataxia telangiectasia (ATM) and CHEK2 genes, with HER-2 positive unilateral breast cancer at 29. The second was a 53-year-old woman carrying PVs in the BRCA1 and CDKN2A genes, who presented with triple-negative breast cancer at 51. We describe their family history and treatment, where the lack of evidence for personalised management becomes evident. Conclusion: Predicting the phenotypic effect of harbouring two variants in CSG is challenging. It is essential to encourage the notification of other cases and carry out functional studies to establish specific risks for affected individuals to develop personalised follow-up guidelines to reduce the associated morbimortality.

ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review.

BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

Ataxia-Telangiectasia Mutated (ATM) gene signaling pathways in human cancers and their therapeutic implications.

Cancer is a multifaceted disease driven by abnormal cell growth and poses a significant global health threat. The multifactorial causes, differences in individual susceptibility to therapeutic drugs, and induced drug resistance pose major challenges in addressing cancers effectively. One of the most important aspects in making cancers highly heterogeneous in their physiology lies in the genes involved and the changes occurring to some of these genes in malignant conditions. The Genetic factors have been implicated in the oncogenesis, progression, responses to treatment, and metastasis. One such gene that plays a key role in human cancers is the mutated form of the Ataxia-telangiectasia gene (ATM). ATM gene located on chromosome 11q23, plays a vital role in maintaining genomic stability. Understanding the genetic basis of A-T is crucial for diagnosis, management, and treatment. Breast cancer, lung cancer, prostate cancer, and gastric cancer exhibit varying relationships with the ATM gene and influence their pathways. Targeting the ATM pathway proves promising for enhancing treatment effectiveness, especially in conjunction with DNA damage response pathways. Analyzing the therapeutic consequences of ATM mutations, especially in these cancer types facilitates the approaches for early detection, intervention, development of personalized treatment approaches, and improved patient outcomes. This review emphasizes the role of the ATM gene in various cancers, highlighting its impact on DNA repair pathways and therapeutic responses.

Oxidative stress and the multifaceted roles of ATM in maintaining cellular redox homeostasis.

The ataxia telangiectasia mutated (ATM) protein kinase is best known as a master regulator of the DNA damage response. However, accumulating evidence has unveiled an equally vital function for ATM in sensing oxidative stress and orchestrating cellular antioxidant defenses to maintain redox homeostasis. ATM can be activated through a non-canonical pathway involving intermolecular disulfide crosslinking of the kinase dimers, distinct from its canonical activation by DNA double-strand breaks. Structural studies have elucidated the conformational changes that allow ATM to switch into an active redox-sensing state upon oxidation. Notably, loss of ATM function results in elevated reactive oxygen species (ROS) levels, altered antioxidant profiles, and mitochondrial dysfunction across multiple cell types and tissues. This oxidative stress arising from ATM deficiency has been implicated as a central driver of the neurodegenerative phenotypes in ataxia-telangiectasia (A-T) patients, potentially through mechanisms involving oxidative DNA damage, PARP hyperactivation, and widespread protein aggregation. Moreover, defective ATM oxidation sensing disrupts transcriptional programs and RNA metabolism, with detrimental impacts on neuronal homeostasis. Significantly, antioxidant therapy can ameliorate cellular and organismal abnormalities in various ATM-deficient models. This review synthesizes recent advances illuminating the multifaceted roles of ATM in preserving redox balance and mitigating oxidative insults, providing a unifying paradigm for understanding the complex pathogenesis of A-T disease.

Post-Integrational DNA Repair of HIV-1 Is Associated with Activation of the DNA-PK and ATM Cellular Protein Kinases and Phosphorylation of Their Targets.

Integration of the DNA copy of HIV-1 genome into the cellular genome results in series of damages, repair of which is critical for successful replication of the virus. We have previously demonstrated that the ATM and DNA-PK kinases, normally responsible for repairing double-strand breaks in the cellular DNA, are required to initiate the HIV-1 DNA postintegrational repair, even though integration does not result in DNA double-strand breaks. In this study, we analyzed changes in phosphorylation status of ATM (pSer1981), DNA-PK (pSer2056), and their related kinase ATR (pSer428), as well as their targets: Chk1 (pSer345), Chk2 (pThr68), H2AX (pSer139), and p53 (pSer15) during the HIV-1 DNA postintegrational repair. We have shown that ATM and DNA-PK, but not ATR, undergo autophosphorylation during postintegrational DNA repair and phosphorylate their target proteins Chk2 and H2AX. These data indicate common signaling mechanisms between the double-strand DNA break repair and postintegrational repair of HIV-1 DNA.

The Effects and Mechanism of ATM Kinase Inhibitors in Toxoplasma gondii.

Toxoplasma gondii, an important opportunistic pathogen, underscores the necessity of developing novel therapeutic drugs and identifying new drug targets. Our findings indicate that the half-maximal inhibitory concentrations (IC50) of KU60019 and CP466722 (abbreviated as KU and CP) against T. gondii are 0.522 µM and 0.702 µM, respectively, with selection indices (SI) of 68 and 10. Treatment with KU and CP affects the in vitro growth of T. gondii, inducing aberrant division in the daughter parasites. Transmission electron microscopy reveals that KU and CP prompt the anomalous division of T. gondii, accompanied by cellular enlargement, nuclear shrinkage, and an increased dense granule density, suggesting potential damage to parasite vesicle transport. Subsequent investigations unveil their ability to modulate the expression of certain secreted proteins and FAS II (type II fatty acid synthesis) in T. gondii, as well as including the dot-like aggregation of the autophagy-related protein ATG8 (autophagy-related protein 8), thereby expediting programmed death. Leveraging DARTS (drug affinity responsive target stability) in conjunction with 4D-Label-free quantitative proteomics technology, we identified seven target proteins binding to KU, implicated in pivotal biological processes such as the fatty acid metabolism, mitochondrial ATP transmission, microtubule formation, and Golgi proteins transport in T. gondii. Molecular docking predicts their good binding affinity. Furthermore, KU has a slight protective effect on mice infected with T. gondii. Elucidating the function of those target proteins and their mechanism of action with ATM kinase inhibitors may potentially enhance the treatment paradigm for toxoplasmosis.

Key molecular DNA damage responses of human cells to radiation.

Our understanding of the DNA damage responses of human cells to radiation has increased remarkably over the recent years although some notable signaling events remain to be discovered. Here we provide a brief account of the key molecular events of the responses to reflect the current understanding of the key underlying mechanisms involved.

ATM and ATR gene editing mediated by CRISPR/Cas9 in Chinese Hamster cells.

Chinese hamster-derived cell lines including Chinese hamster lung fibroblasts (V79) have been used as model somatic cell lines in radiation biology and toxicology research for decades and have been instrumental in advancing our understanding of DNA damage response (DDR) mechanisms. Whereas many mutant lines deficient in DDR genes have been generated more than over decades, several key DDR genes such as ATM and ATR have not been established in the Chinese hamster system. Here, we transfected CRISPR/Cas9 vectors targeting Chinese hamster ATM or ATR into V79 cells and investigated whether the isolated clones had the characteristics reported in human and mouse studies. We obtained two clones of ATM knockout cells containing an insertion or deletions in the targeted locus. The ATM knockouts with no detectable ATM protein expression exhibited increased sensitivity to radiation and DNA double strand break inducing agents, cell cycle checkpoint defects and defective chromatid break repair. These are all characteristics of defective ATM function. Among the obtained ATR cells, which contained mutations in both ATR alleles while maintaining normal levels of ATR protein expression, one clone exhibited hypersensitivity to UV and replication stress agents. In the present study, we successfully established CRISPR-Cas9 derived ATM knockout cells. We couldn't knock out the ATR gene but obtained ATR mutant cells. Our results showed that Chinese hamster origin ATM knockout cells and ATR mutant cells could be useful tools for further research to reveal oncogenic functions and effects of developing anti-cancer therapeutics.

Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

BACKGROUND AND AIM: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients. METHODS: Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A. RESULTS: 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1-2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients. CONCLUSIONS: A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1-2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.

Oromandibular dystonia as a cause of temporomandibular disorder (Case report) / Distonia oromandibular como causa de disfunção temporomandibular (Relato de caso)

Temporomandibular disorders (TMD) can have multiple etiologies, including oromandibular dystonia (OMD). However, in a few cases, the OMD can evolve from cervical dystonia (CD), leading to severe bone degeneration. The purpose of this case report of a 64-year-old woman presenting to the Outpatient Neurology Clinic of the Federal University of Bahia is to illustrate the development of oromandibular dystonia with temporomandibular joint (TMJ) dysfunction after 10 years of cervical dystonia. Clinical examination showed bone degeneration of the mandibular ramus and right TMJ click, a prevalent sound in patients with temporomandibular disorders when they open their mouths or chew. After onabotulinum toxin type A injections in the right lateral pterygoid muscle, the patient improved in swallowing and pain. This case highlights the importance of close follow-up of cervical dystonia patients to identify new dystonic muscles. In our patient, lateral pterygoid muscle involvement was followed by several comorbidities, such as dysphagia and jawbone abnormalities.

Os distúrbios temporomandibulares (DTM) podem ter múltiplas etiologias, incluindo a distonia oromandibular (DO). No entanto, em raros casos, a DO pode evoluir a partir da distonia cervical (DC) e raramente pode levar a degeneração óssea. O objetivo deste relato de caso de uma mulher de 64 anos atendida no Ambulatório de Neurologia da universidade Federal da Bahia é ilustrar o desenvolvimento de distonia oromandibular com disfunção da articulação temporomandibular (ATM) após 10 anos de distonia cervical. O exame clínico mostrou degeneração óssea do ramo mandibular e clique na ATM direita, um som prevalente em pacientes com distúrbios temporomandibulares quando abrem a boca ou mastigam. Após injeções de toxina botulínica tipo A no músculo pterigoideo lateral direito, a paciente apresentou melhora na deglutição e na dor. Este caso destaca a importância do acompanhamento próximo de pacientes com distonia cervical para identificar novos músculos distônicos. Em nossa paciente, o envolvimento do músculo pterigoide lateral foi seguido por várias comorbidades, como disfagia e anormalidades ósseas da mandíbula.