Table 2 Revised C4CMMRD indication criteria for CMMRD testing in cancer patientsa.

From: ERN GENTURIS guidelines on constitutional mismatch repair deficiency diagnosis, genetic counselling, surveillance, quality of life, and clinical management

CMMRD testing is indicated in a cancer patient reaching ≥ 3 points.

C4CMMRD scoring points assigned to (pre-)malignancies in the patient (at least one point is mandatory):

 Carcinoma of the Lynch syndrome (LS) spectrumb and/or a high-grade dysplastic adenoma of the digestive tract at age < 25 years

3 points

 Multiple colorectal adenomas at age < 25 years and no genetic diagnosis/explanation upon testing for polyposis syndromes

3 points

 T-cell lymphoblastic lymphoma (T-LBL) at age < 18 years

2 points

 WHO grade III or IV glioma at age < 25 years

2 points

 Any other malignancy at age < 18 years

1 point

C4CMMRD scoring points assigned to additional features in the patient (optional):

 Clinical sign of Neurofibromatosis type 1 (NF1)c and/or ≥4 hyperpigmented and/or hypopigmented skin alterations with Ød >1 cm

2 points

 2 or 3 hyperpigmented and/or hypopigmented skin alterations with Ø >1 cm (Do not count if two points are already given for “Clinical sign of NF1 and/or ≥ 4 hyperpigmented and/or hypopigmented skin alterations with Ø >1 cm”)

1 point

 Multiple pilomatrixomas

2 points

 One pilomatrixoma

1 point

 Agenesis of the corpus callosum

1 point

 Non-therapy-induced cavernoma

1 point

 Multiple developmental venous anomalies (DVAs, also known as cerebral venous angiomas) in separate regions of the brain

2 points

 Paediatric systemic lupus erythematosus

1 point

 Deficiency/reduced levels of IgG2/4 and/or IgA

1 point

C4CMMRD scoring points assigned to additional features in the family (optional):

 Consanguineous parents

1 point

 Diagnosis of LS in a first-degree or second-degree relative

2 points

 Carcinoma from LS spectrumb before the age of 60 years in a first-degree, second-degree, and/or third-degree relative

1 point

 A sibling with a (pre-)malignancy assigned two or three C4CMMRD scoring points

2 points

 A sibling with any type of childhood malignancy

1 point

  1. C4CMMRD Care for CMMRD, (L)PV(s) (likely) pathogenic variant(s), WHO World Health Organization, NF1 Neurofibromatosis type 1.
  2. aOriginal C4CMMRD criteria: Wimmer et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘care for CMMRD’ (C4CMMRD). J Med Genet 2014; 51(6):355-65.
  3. bColorectal, endometrial, small bowel, urothelial, gastric, ovarian, and biliary tract cancer.
  4. cClinical sign in the patient used for the diagnosis of NF1 according to: Legius et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med 2021; 23(8):1506–1513.
  5. dDiameter.
Back to article page