Dermatological Manifestations of Inherited Cancer Syndromes in Children

A. Karalis; M. Tischkowitz; G.W.M. Millington


The British Journal of Dermatology. 2011;164(2):245-256. 

In This Article

Mismatch Repair Defects

Constitutional Mismatch Repair Deficiency Syndrome

A mutation in one allele of the four described MMR genes MLH1, MSH2, MSH6 or PMS2 causes Lynch syndrome (autosomal dominant), also known as hereditary nonpolyposis colon cancer.[11,12] This is associated with carcinoma of the colon, stomach, endometrium, pancreaticobiliary system and urinary tract, respectively,[11,12] with few cutaneous associations[11,12] except for Muir–Torre syndrome, a form of Lynch syndrome associated with sebaceous skin tumours.[2]

Homozygous or compound heterozygous inheritance of mutations in both alleles of an MMR gene is associated with a distinct phenotype, characterized by haematological malignancy, rhabdomyosarcoma, brain tumours, and very early onset gastrointestinal tumours.[11–13] This is known as constitutional mismatch repair deficiency syndrome (CMMR-D).[11,12] CMMR-D often presents with multiple CALMs.[11,12] The CALMs in CMMR-D usually differ from those in neurofibromatosis type 1 (NF1) in that they have ragged-edged, irregular borders,[11,14] but in some families they are indistinguishable from those of NF1.[12] Screening for gastrointestinal malignancies in CMMR-D is essential and the clinician needs to be aware of the association with haematological and brain malignancies.[11,12] Relatives found to be heterozygous carriers should be monitored as per Lynch syndrome surveillance protocols.[11]


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