Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort

Abstract

In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

“…This extremely high mortality rate also confirms that CMMRD has to be diagnosed in a timely fashion to allow tumor surveillance, and that adapted chemotherapies are necessary to treat the different highly resistant childhood cancers occurring in this group of patients. 9,47 In contrast, patients with XLP (n=11) and WAS (n=7), mainly suffering from mature B-cell NHL (5 of 11 and 2 of 5 with DLBCL), had a comparatively good outcome with 70%-90% of the patients in first CR. Among the other diagnoses of cancer predisposition syndromes, death from therapy-related complications accounted for most events.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Primary immunodeficiencies (PID) such as DNA repair defects (Nijmegen breakage syndrome, Ataxia telangiectasia, Bloom syndrome or constitutional mismatch repair deficiency), severe combined immunodeficiencies (SCID), common variable immunodeficiencies (CVID), and immune-osseous dysplasias (Di George syndrome or cartilage hair hypoplasia) have an extraordinary risk of developing leukemia and lymphoma. [5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes.…”

Seltene Tumordispositionssyndrome mit Manifestation im Kindesalter

“…Nahezu alle Patienten entwickeln in der zweiten bis dritten Lebensdekade auch einzelne bis zahlreiche adenomatöse Polypen in Dick-und Dünndarm, die gegebenenfalls differentialdiagnostisch von einer FAP abgegrenzt werden müssen [49]. Eine Fülle anderer Krebserkrankungen (zum Beispiel embryonale Tumoren, Sarkome und andere) wurde im CMMRDKontext beschrieben [47,50]. Multiple Pilomatrixome können auf eine CMMRD-Erkrankung hinweisen, treten aber auch im Kontext anderer TDS auf [47,51].…”

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

“…The most common are malignant brain tumors, followed by gastrointestinal and hematologic malignancies. The median ages at diagnosis of hematologic malignancies and brain tumors have been estimated to be 6.6 and 10.3 years, respectively (12). Most brain tumors are malignant gliomas, although low-grade lesions have been observed.…”

“…Furthermore, recent data reveal a large variety of other cancers and multi-organ involvement. These include childhood sarcomas such as osteosarcoma and rhabdomyosarcoma (12), other childhood cancers such as neuroblastoma and Wilms tumor, and genitourinary cancers usually seen in adults with LS. These tumors occur even in the first decade of life, although sarcomas and genitourinary cancers are also observed in the second decade.…”