Although colorectal cancer in children is rare, this case demonstrates that advanced disease can be diagnosed in the pediatric population. In these cases, the suspicion of genetic syndromes is important. In our patient, the presence of some typical features such as parental consanguinity and the presence of café-au-lait macules triggered further investigation into genetic diseases.
It is extremely important to recognize BMMRD given its association with additional cancers including small-bowel cancer, central nervous system tumors, hematologic malignancies and, rarely, urinary tract tumors. The European consortium “Care 4 CMMRD” published guidelines for diagnosis of BMMRD in 2014 , based on the knowledge of the disease from just 146 known patients. In 2017, US Multi-Society Task Force on Colorectal Cancer  expanded upon these guidelines with further diagnostic and surveillance recommendations for this vulnerable population.
Biallelic mutations have been reported in all four DNA MMR genes (MLH1, MSH2, MSH6, and PMS2). However, the majority of BMMRD patients with gastrointestinal (GI) cancers report biallelic mutations in PMS2. In classic LS, monoallelic carriers of PMS2 variants have a lower penetrance for GI cancers. The combination of the early-onset cancer in the proband, later-onset cancer in the parents, and incomplete penetrance for PMS2-LS leads to a family history that is often negative. This may also explain how two unrelated healthy individuals with heterozygote PMS2 variants would remain unaffected and produced offspring without being aware of his/her own risk of cancer development .
In our case, once the diagnosis of BMMRD was established, close surveillance of the young boy and his parents was instituted. This allowed the early diagnosis and management of a new tumor in our patient.
It is important to be familiar with and know how to identify the genetic cause in patients and their family members as it provides information pertinent to lifelong medical screening. It is paramount for clinicians to always recognize the potential for a rare disease diagnosis both to provide the best care for our patients and to expand the knowledge and recognition of disorders such as BMMRD.