De novo TRPV4 Leu619Pro variant causes a new channelopathy characterised by giant cell lesions of the jaws and skull, skeletal abnormalities and polyneuropathy.

BACKGROUND: Pathogenic germline variants in Transient Receptor Potential Vanilloid 4 Cation Channel (TRPV4) lead to channelopathies, which are phenotypically diverse and heterogeneous disorders grossly divided in neuromuscular disorders and skeletal dysplasia. We recently reported in sporadic giant cell lesions of the jaws (GCLJs) novel, somatic, heterozygous, gain-of-function mutations in TRPV4, at Met713. METHODS: Here we report two unrelated women with a de novo germline p.Leu619Pro TRPV4 variant and an overlapping systemic disorder affecting all organs individually described in TRPV4 channelopathies. RESULTS: From an early age, both patients had several lesions of the nervous system including progressive polyneuropathy, and multiple aggressive giant cell-rich lesions of the jaws and craniofacial/skull bones, and other skeletal lesions. One patient had a relatively milder disease phenotype possibly due to postzygotic somatic mosaicism. Indeed, the TRPV4 p.Leu619Pro variant was present at a lower frequency (variant allele frequency (VAF)=21.6%) than expected for a heterozygous variant as seen in the other proband, and showed variable regional frequency in the GCLJ (VAF ranging from 42% to 10%). In silico structural analysis suggests that the gain-of-function p.Leu619Pro alters the ion channel activity leading to constitutive ion leakage. CONCLUSION: Our findings define a novel polysystemic syndrome due to germline TRPV4 p.Leu619Pro and further extend the spectrum of TRPV4 channelopathies. They further highlight the convergence of TRPV4 mutations on different organ systems leading to complex phenotypes which are further mitigated by possible post-zygotic mosaicism. Treatment of this disorder is challenging, and surgical intervention of the GCLJ worsens the lesions, suggesting the future use of MEK inhibitors and TRPV4 antagonists as therapeutic modalities for unmet clinical needs.

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A.

The thyroid hormone receptor interactor 11 (TRIP11) gene encodes the Golgi microtubule-associated protein 210 (GMAP-210), a protein essential for the operation of the Golgi apparatus. It is known that null mutations in TRIP11 disrupt Golgi function and cause a lethal skeletal dysplasia known as achondrogenesis type 1A (ACG1A), however recently, hypomorphic mutations in that gene have been linked to odontochondrodysplasia (ODCD), a nonlethal skeletal dysplasia characterized by skeletal changes in the spine and in the metaphyseal regions, associated with dentinogenesis imperfecta. Here we present two patients reflecting the phenotypic spectrum related to different TRIP11 variants. The first is a female child with ODCD, for whom a homozygous in-frame splicing mutation in intron 9 of TRIP11 was identified. The mutation appears to lead to the expression of an alternative TRIP11 transcript, that may explain the less severe radiological alterations in ODCD. The second is a fetus with classical form of ACG1A, associated with typical molecular findings (frameshift) in exon 11 of TRIP11, both novel mutations. The two patients reported here represent the TRIP11 spectrum of skeletal dysplasia ranging from mild to lethal phenotypes, thereby enabling one to suggest a genotype-phenotype correlation in these diseases.

Breast metastasis around dental implants: a case report.

BACKGROUND: Metastases to the oral cavity and to the jaws are rare; hence, the clinical manifestations of the oral metastasis lesion could frequently be simulating general pathologic entities, making the diagnosis a challenging process to the dental team. Local factors, such as trauma, have been observed to facilitate the growth of blood-borne tumors. To this end, surgical procedures such as fixture placement might cause cancer cells to spread. PURPOSE: Careful clinical examination is a valuable help in diagnosing oral lesions, which can improve the quality of life of patients and reduce the risks of oral complications. MATERIALS AND METHODS: A female patient was referred to the clinic with symptoms of irritation, swelling, and pain associated with implants in the mandible and the maxilla. RESULTS: Clinical examination, x-ray, and histopathology revealed that the patients suffered from a metastatic lesion, primary tumor being an adenocarcinoma of the breast diagnosed at the same time. CONCLUSION: Optimal clinical examination in conjunction with radiography and histopathology is a necessity in order to discover malignant lesions in time. Routine dental check-ups must comprise more thorough soft-tissue examination.

Management of chemo- and radiotherapy induced oral mucositis with low-energy laser: initial results of A.C. Camargo Hospital / Manejo da mucosite oral induzida por quimioterapia e radioterapia com laser de baixa potência: resultados iniciais do Hospital A.C. Camargo

Mucosite é a complicação oral mais comum do tratamento de algumas doenças malignas, podendo causar a necessidade de modificações terapêuticas, o que pode interferir com o prognóstico da doença. Muitas tentativas têm sido feitas com o intuito de desenvolver um tratamento ou método preventivo para minimizar a severidade da mucosite oral. Vários estudos têm mostrado bons resultados com o uso do laser de baixa potência, devido à aceleração do processo de cicatrização das lesões e da promoção do alívio da dor. Métodos: Os pacientes que desenvolveram mucosite oral durante tratamento quimioterápico e/ou radioterápico (n=18), foram submetidos a aplicações de laser de baixa potência até que fosse atingida a cessação dos sintomas. A severidade da mucosite foi avaliada através de uma escala baseada em características clínicas e de uma escala para avaliação de toxicidade oral desenvolvida pelo Instituto Nacional do Cancer, baseada na habilidade de deglutição; a dor foi avaliada através de uma escala visual, antes e depois de cada aplicação. Resultados: Alívio imediato da dor após a primeira aplicação foi referido por 66.6 por cento dos pacientes. Com base na escala funcional, mucosite grau III (incapacidade de ingerir alimentos sólidos) foi reduzida em 42.85 por cento dos casos. De acordo com a escala baseada em aspectos clínicos, mucosite grau IV (presença de úlceras) foi reduzida em 75 por cento dos pacientes que apresentavam essa condição no início da terapia com laser. Conclusões: O laser de baixa potência foi bem tolerado pelos pacientes, e mostrou efeitos benéficos durante o manejo da mucosite oral, melhorando a qualidade de vida dos pacientes durante o tratamento oncológico.

Aspectos clínicos, radiográficos e terapêuticos do ameloblastoma / Clinical, radiological and therapeutcs aspects of ameloblastoma

Neste trabalho, foram avaliados 52 pacientes diagnosticados histopatologicamente com ameloblastoma na região maxilo-mandibular e tratados no Departamento de Estomatologia do Centro de Tratamento e Pesquisa do Hospital do Câncer - A. C. Camargo, no período de 1960 a 2001. Foram avaliadas as características radiográficas, clínicas, terapêuticas e taxas de recidivas. Não houve um predomínio em relação ao gênero e etnia na amostra estudada. As idades de diagnóstico da lesão variaram de 6 a 73 anos. As características radiográficas do ameloblastoma de maior incidência são de uma lesão multilocular, no ramo ascendente da mandíbula, com limites expansivos, preservando a cortical basilar. O modo de tratamento mais utilizado foi conservador: curetagem associada à crioterapia. A taxa de recidiva encontrada não foi diferente das encontradas nos tratamentos radicais dessa lesão.