Paediatric systemic lupus erythematosus as a manifestation of constitutional mismatch repair deficiency

Toledano, Helen; Orenstein, Naama; Sofrin, Efrat; Ruhrman‐Shahar, Noa; Amarilyo, Gil; Basel‐Salmon, Lina; Shuldiner, Alan R.; Smirin‐Yosef, Pola; Aronson, Melyssa; Al-tarrah, Hibs; Bazak, Lili; Gonzaga‐Jauregui, Claudia; Tabori, Uri; Wimmer, Katharina; Goldberg, Yael

doi:10.1136/jmedgenet-2019-106303

Cited by 10 publications

(9 citation statements)

References 22 publications

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“…At the meeting, Yael Goldberg introduced a new non-neoplastic feature by presenting two cases of young children with CMMRD and pediatric systemic lupus erythematosus (SLE). Age of onset was 5 years in both children, and one child did not have any cancer at the time of diagnosis [12]. Together with three previously described children with CMMRD and SLE [13][14][15], these cases indicate that pediatric onset SLE should be considered a diagnostic criterion of CMMRD, and CMMRD testing should be offered if additional features are present [1].…”

Section: Cmmrd and Early-onset Systemic Lupus Erythematosussupporting

confidence: 53%

Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019

et al. 2020

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Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessive condition associated with a high risk of cancer in children, adolescents and young adults. CMMRD is caused by homozygous or compound heterozygous pathogenic germline variants in one of four mismatch repair (MMR) genes (i.e., MLH1, MSH2, MSH6 and PMS2) [1], whereas mono-allelic (heterozygous) MMR gene variants result in autosomal dominant Lynch syndrome [2]. Lynch syndrome is one of the most common cancer predisposition syndromes and in adults leads to an increased risk of colorectal cancer, endometrial cancer and other malignancies [2]. By contrast, CMMRD is rare and leads to an increased risk of brain tumors, hematological malignancies, colorectal cancer and a wide range of other cancers in children, adolescents and young adults [1]. In addition, most patients with CMMRD have non-neoplastic features, with multiple café-au-lait maculae (CALM) being the most prevalent [1, 3]. This report summarizes the 5th meeting held by the 'Care for CMMRD' (C4CMMRD) consortium in Leiden, the Netherlands, on July 6th 2019. The consortium was established in 2013 with a number of explicit goals, including

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Section: Cmmrd and Early-onset Systemic Lupus Erythematosussupporting

confidence: 53%

Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019

et al. 2020

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“…However, 5 previously reported patients with both pediatric systemic lupus erythematosus and CMMRD out of about 200 total cases of CMMRD in the literature have been found 5 . Unlike these previously reported patients who were all female, our patient is a male patient with SLE preceding hematologic malignancy leading to the diagnosis of CMMRD 5 …”

Section: Discussionmentioning

confidence: 56%

“…Despite the role of MMR proteins in immunoglobulin class‐switch recombination and somatic hypermutations, neither immunodeficiencies nor autoimmunity are common findings in CMMRD 5,6 . However, 5 previously reported patients with both pediatric systemic lupus erythematosus and CMMRD out of about 200 total cases of CMMRD in the literature have been found 5 .…”

Section: Discussionmentioning

confidence: 99%

Eruptive nevi in a patient with constitutional mismatch repair deficiency (CMMRD)

Vassantachart

Zacher

Teng

2021

Pediatric Dermatology

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Biallelic mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6, or PMS2 result in one of the most aggressive genetic cancer conditions, constitutional mismatch repair syndrome (CMMRD). We present a case of a 10‐year‐old boy with biallelic MSH6 mutation and systemic lupus erythematosus with eruptive melanocytic nevi after receiving chemotherapy for mediastinal T‐cell lymphoblastic lymphoma.

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“…Other clinical features reported in CMMRD patients include agenesis of the corpus callosum, grey matter heterotopia 47 , venous anomalies 48 , multiple pilomatrixoma 49 , paediatric systemic lupus erythematosus 50 , intracranial tuber-like lesions and renal angiomyolipoma. 51 Decreased IgA and/or IgG2/4 levels 1 have also been reported, however, this was not substantiated in a recent study that could not consistently identify clinical or routine immunological laboratory parameters suggestive of primary immunodeficiency in 15 unrelated CMMRD patients.…”

Section: Cii) Benign Manifestationsmentioning

confidence: 99%

Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group

et al. 2021

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BackgroundConstitutional mismatch repair deficiency syndrome (CMMRD) is the most aggressive cancer predisposition syndrome associated with multiorgan cancers, often presenting in childhood. There is variability in age and presentation of cancers and benign manifestations mimicking neurofibromatosis type 1. Genetic testing may not be informative and is complicated by pseudogenes associated with the most commonly associated gene, PMS2. To date, no diagnostic criteria exist. Since surveillance and immune-based therapies are available, establishing a CMMRD diagnosis is key to improve survival.MethodsIn order to establish a robust diagnostic path, a multidisciplinary international working group, with representation from the two largest consortia (International Replication Repair Deficiency (IRRD) consortium and European Consortium Care for CMMRD (C4CMMRD)), was formed to establish diagnostic criteria based on expertise, literature review and consensus.ResultsThe working group established seven diagnostic criteria for the diagnosis of CMMRD, including four definitive criteria (strong evidence) and three likely diagnostic criteria (moderate evidence). All criteria warrant CMMRD surveillance. The criteria incorporate germline mismatch repair results, ancillary tests and clinical manifestation to determine a diagnosis. Hallmark cancers for CMMRD were defined by the working group after extensive literature review and consultation with the IRRD and C4CMMRD consortia.ConclusionsThis position paper summarises the evidence and rationale to provide specific guidelines for CMMRD diagnosis, which necessitates appropriate surveillance and treatment.

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Paediatric systemic lupus erythematosus as a manifestation of constitutional mismatch repair deficiency

Cited by 10 publications

References 22 publications

Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019

Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019

Eruptive nevi in a patient with constitutional mismatch repair deficiency (CMMRD)

Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group

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