ABSTRACT
Dissemination in pediatric low-grade glioma may occur in about 4%-10% of patients according to retrospective cohort studies. Due to its low incidence, there is no consensus on treatment for these patients. According to the constitutional activation of the MAPK/ERK pathway in these tumors, MEK inhibitors such as trametinib have been used successfully in the relapsed setting. Skin toxicity is frequent in patients receiving trametinib, normally mild to moderate, but sometimes severe, needing to discontinue the drug, limiting the efficacy in the tumor. There is not much information in the literature regarding whether reducing the dose of trametinib is able to maintain efficacy while, at the same time, decreasing toxicity. Here, we present an adolescent, with severe skin toxicity, whose trametinib dose was reduced by 50% and efficacy on the tumor continued while skin toxicity significantly decreased.
ABSTRACT
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare and extraordinarily penetrant childhood-onset cancer predisposition syndrome. Genetic diagnosis is often hampered by the identification of mismatch repair (MMR) variants of unknown significance and difficulties in PMS2 analysis, the most frequently mutated gene in CMMRD. We present the validation of a robust functional tool for CMMRD diagnosis and the characterization of microsatellite instability (MSI) patterns in blood and tumors. METHODS: The highly sensitive assessment of MSI (hs-MSI) was tested on a blinded cohort of 66 blood samples and 24 CMMRD tumor samples. Hs-MSI scores were compared with low-pass genomic instability scores (LOGIC/MMRDness). The correlation of hs-MSI scores in blood with age of cancer onset and the distribution of insertion-deletion (indel) variants in microsatellites were analyzed in a series of 169 individuals (n = 68 CMMRD, n = 124 non-CMMRD). RESULTS: Hs-MSI achieved high accuracy in the identification of CMMRD in blood (sensitivity 98.5% and specificity 100%) and detected MSI in CMMRD-associated tumors. Hs-MSI had a strong positive correlation with whole low-pass genomic instability LOGIC scores (r = 0.89, P = 2.2e-15 in blood and r = 0.82, P = 7e-3 in tumors). Indel distribution identified PMS2 pathogenic variant (PV) carriers from other biallelic MMR gene PV carriers with an accuracy of 0.997. Higher hs-MSI scores correlated with younger age at diagnosis of the first tumor (r = -0.43, P = 0.011). CONCLUSIONS: Our study confirms the accuracy of the hs-MSI assay as ancillary testing for CMMRD diagnosis, which can also characterize MSI patterns in CMMRD-associated cancers. Hs-MSI is a powerful tool to pinpoint PMS2 as the affected germline gene and thus potentially personalize cancer risk.
Subject(s)
Germ-Line Mutation , Microsatellite Instability , Mismatch Repair Endonuclease PMS2 , Humans , Mismatch Repair Endonuclease PMS2/genetics , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/diagnosis , Brain Neoplasms/genetics , Brain Neoplasms/diagnosis , Child , Colorectal Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Female , Male , DNA Mismatch Repair/genetics , Child, Preschool , Adolescent , AllelesABSTRACT
INTRODUCTION: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, infection prevention measures were enforced at our Pediatric Neuro-Oncology unit. METHODS: A retrospective study analyzing patients booked in this unit during lockdown was performed to describe its performance. RESULTS: There were 438 consultations for 123 patients (320 on-site/118 telephone). Eight new diagnoses were made, with one significant delay. Only one patient tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delay in imaging testing occurred in 15 patients. Chemotherapy was delayed in one case. There were no delays in radiotherapy. CONCLUSIONS: Measures implemented were effective in minimizing the risk of COVID-19 infection, achieving continuity in diagnoses and treatment, and avoiding delays that could impact survival.
Subject(s)
COVID-19 , Pandemics , Child , Humans , Pandemics/prevention & control , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Communicable Disease ControlABSTRACT
La incontinencia pigmenti es un trastorno neurocutàneo raro, con una frecuencia de 1 en 40 000 recién nacidos, de etiología genética asociada a mutaciones en el gen IKBKG, localizado en Xq28, con herencia dominante ligada al X. Tiene una presentación clínica de manifestaciones muy variables detectadas desde la etapa neonatal y puede asociar afectación cutànea, dental, ocular y neurológica, y cada una de estas con un diagnóstico diferencial distinto. Se presenta a una paciente pediàtrica con diagnóstico de incontinencia pigmenti a la semana de vida. En la evaluación oftalmológica inicial, se observaron lesiones vasculares retinianas. Se decidió el tratamiento con làser, con buenos resultados, y se consiguió estabilizar la visión.
Incontinentia pigmenti is a rare neurocutaneous disorder with a frequency of 1 in 40,000 newborn; it is associated with mutations in IKBKG gene in Xq28, inherited as an X-linked dominant trait. Clinical manifestations detected since the newborn period are highly variable, with skin, teeth, eyes, and nervous system manifestations, and each with a characteristic differential diagnosis. We present a pediatric patient diagnosed with incontinentia pigmenti at the first week of life. In the initial ophthalmologic evaluation, retinal vascular lesions were observed. The outcomes of laser treatment of the ischemic peripheral retina were good and resulted in stability of vision.
Subject(s)
Humans , Female , Infant, Newborn , Pediatrics , Incontinentia Pigmenti , Eye Manifestations , Laser Therapy , Vascular System InjuriesABSTRACT
Incontinentia pigmenti is a rare neurocutaneous disorder with a frequency of 1 in 40,000 newborn; it is associated with mutations in IKBKG gene in Xq28, inherited as an X-linked dominant trait. Clinical manifestations detected since the newborn period are highly variable, with skin, teeth, eyes, and nervous system manifestations, and each with a characteristic differential diagnosis. We present a pediatric patient diagnosed with incontinentia pigmenti at the first week of life. In the initial ophthalmologic evaluation, retinal vascular lesions were observed. The outcomes of laser treatment of the ischemic peripheral retina were good and resulted in stability of vision.
La incontinencia pigmenti es un trastorno neurocutàneo raro, con una frecuencia de 1 en 40 000 recién nacidos, de etiología genética asociada a mutaciones en el gen IKBKG, localizado en Xq28, con herencia dominante ligada al X. Tiene una presentación clínica de manifestaciones muy variables detectadas desde la etapa neonatal y puede asociar afectación cutànea, dental, ocular y neurológica, y cada una de estas con un diagnóstico diferencial distinto. Se presenta a una paciente pediàtrica con diagnóstico de incontinencia pigmenti a la semana de vida. En la evaluación oftalmológica inicial, se observaron lesiones vasculares retinianas. Se decidió el tratamiento con làser, con buenos resultados, y se consiguió estabilizar la visión.
Subject(s)
Incontinentia Pigmenti/complications , Laser Therapy/methods , Retinal Diseases/therapy , Diagnosis, Differential , Female , Humans , Incontinentia Pigmenti/diagnosis , Infant, Newborn , Retinal Diseases/diagnosis , Retinal Diseases/etiology , Treatment OutcomeABSTRACT
No disponible
Subject(s)
Humans , Female , Child , Anemia, Aplastic/drug therapy , Treatment Outcome , Benzoates/therapeutic use , Hydrazines/therapeutic use , Pyrazoles/therapeutic use , Receptors, Thrombopoietin/agonists , Anemia, Aplastic/pathology , Benzoates/adverse effects , Hydrazines/adverse effects , Pyrazoles/adverse effects , Severity of Illness IndexSubject(s)
Anemia, Aplastic/drug therapy , Benzoates/therapeutic use , Hydrazines/therapeutic use , Pyrazoles/therapeutic use , Receptors, Thrombopoietin/agonists , Anemia, Aplastic/pathology , Benzoates/adverse effects , Child , Female , Humans , Hydrazines/adverse effects , Pyrazoles/adverse effects , Severity of Illness IndexABSTRACT
No disponible
