Constitutional Microsatellite Instability, Genotype, and Phenotype Correlations in Constitutional Mismatch Repair Deficiency.

Background & Aims: Constitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair variants. Constitutional microsatellite instability (cMSI) is a CMMRD diagnostic hallmark and may associate with cancer risk. We quantified cMSI in a large CMMRD patient cohort to explore genotype-phenotype correlations using novel MSI markers selected for instability in blood.

Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.

[What follow-up after pediatric cancer ? The SALTO consultation experience].

During the past 50 years, the mortality due to childhood cancers decreased dramatically thanks to improvements in supportive care and the use of multimodal approaches. In this context, the long-term follow up after childhood cancer has become a main concern for pediatric oncologists. The SALTO programme was developed in 2012 at the CHR Citadelle in Liège in order to organize a multidisciplinary long-term follow-up for the patients previously treated in our department for a childhood cancer.

[The rise of targeted therapies in pediatric oncology].

Cancers are rare pathologies in children. Improvement in survival rates has been obtained thanks to new therapeutic strategies based on the identification of risk factors. Targeted therapies in paediatric oncology are new treatments providing hope that cure is achievable without long-term sequelae.

[Coexistence of sickle cell disease and systemic lupus erythematosus].

Sickle cell disease and systemic lupus erythematosus (SLE) are two distinct chronic conditions sharing many clinical manifestations. Coexisting of these two diseases is rare, but it is important to make the diagnosis of SLE in sickle cell patients to initiate appropriate treatment and limit the risk of complications. High titers of autoantibodies have been reported in sickle cell patients as well as a higher risk of immune deficiency.

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score.

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.

Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.

Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.

High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers.

Introduction: Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary cancer syndromes associated with mismatch repair (MMR) deficiency. Tumours show microsatellite instability (MSI), also reported at low levels in non-neoplastic tissues. Our aim was to evaluate the performance of high-sensitivity MSI (hs-MSI) assessment for the identification of LS and CMMRD in non-neoplastic tissues.

[Epidemiology of childhood cancer, a single-center study (1985-2016)].

Cancer is the second leading cause of death among children aged 5 to 14, after accidents. We conducted a study on the epidemiology of childhood cancer in the university pediatric oncology department of the CHU-CHR in Liège, Belgium. We studied a cohort of 662 patients between the ages of 0 and 17 whose malignancy diagnosis was made between 1985 and 2016.

A sensitive and scalable microsatellite instability assay to diagnose constitutional mismatch repair deficiency by sequencing of peripheral blood leukocytes.

Constitutional mismatch repair deficiency (CMMRD) is caused by germline pathogenic variants in both alleles of a mismatch repair gene. Patients have an exceptionally high risk of numerous pediatric malignancies and benefit from surveillance and adjusted treatment. The diversity of its manifestation, and ambiguous genotyping results, particularly from PMS2, can complicate diagnosis and preclude timely patient management.

Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group.

Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%).

Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.

Background: Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV).

Methods: We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years.

Osteopetrosis mimicking juvenile myelomonocytic leukemia.

A 5-month-old boy developed splenomegaly, anemia, thrombocytopenia with elevated white cells, monocytosis and immature granulocytes in the peripheral blood. Bone marrow showed dysplasia without blastosis. Increased colony-forming unit-granulocyte-macrophage was found in the peripheral blood, mimicking granulocyte-macrophage colony-stimulating factor hypersensitivity.

Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients.

Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum immunoglobulin (Ig) M, low IgM antibody production in response to S pneumoniae following nonconjugated immunization, and low blood memory B-cells counts (including marginal zone [MZ] B-cell counts).

Pneumococcal antibody levels in children with PID receiving immunoglobulin.

Objectives: Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization.

Methods: Patients received 7 consecutive IVIG infusions.

Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes.

Background: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes.

Methods: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions.

Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation.

Paravertebral malignant tumors constitute 4.8% of cancer cases in pediatric oncology and are mostly composed of neuroblastoma (46.4%) and soft tissue sarcomas (35.

Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.

Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected.

A case of osteosarcoma in a patient with pycnodysostosis.

Pycnodysostosis is a rare sclerosing bone dystrophy. The main clinical features are short stature and oral and maxillofacial abnormalities such as a large head, a small and underdeveloped face with prominent nose and eyes, irregular dentition, small hands and feet with dystrophic nails, and trunk deformities such as scoliosis. The differential diagnosis is established with other skeletal dysplasias such as osteopetrosis, cleidocranial dysplasia, and idiopathic acro-osteolysis.

A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation.

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce.

Mevalonate kinase deficiency: a survey of 50 patients.

Objective: The goal of this study was to describe the spectrum of clinical signs of mevalonate kinase deficiency (MKD).

Methods: This was a retrospective French and Belgian study of patients identified on the basis of MKD gene mutations.

Results: Fifty patients from 38 different families were identified, including 1 asymptomatic patient.

[Borrelia-associated lymphocytoma cutis].

We describe a 6-year-old boy who developed Borrelia burgdorferi-associated lymphocytoma cutis on the ear. Lymphocytoma is a benign polyclonal B-cell lymphoproliferative process; it is defined as a subacute manifestation of early disseminated borrelial infection. Clinical history, physical examination, and serodiagnosis tests are often sufficient to establish diagnosis, but sometimes, histopathologic analysis is needed to exclude malignant cutaneous lymphomas.

[Renal tumors in children. A single center study of 31 cases].

In order to illustrate epidemiologic features and survival rate, 31 Wilm's tumours treated in our institution have been retrospectively studied. The mean age at diagnosis in our series was surprisingly higher than usually described: 25% of the patients were older than 8 years. Moreover, a mesoblastic nephroma congenital kidney tumour--appeared in a 10 month old girl.