Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation

Abstract

We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues. His parents were found to be carriers of a nonsense mutation of the PMS2 gene.

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome

“…ACC was previously reported in only one CMMR-D patient with anaplastic astrocytoma and a very early colorectal cancer with an inferred homozygous PMS2 mutation (patient 4 in Table 1). 29 With the present report, there are now at least 4 out of the 115 published CMMR-D cases who show these cerebral malformations. Sixty of those had a brain tumor and therefore presumably had comprehensive imaging of the central nervous system.…”

Colorectal Cancer in People with Intellectual Disabilities

“…Other case studies have revealed at least 3 patients (2 male, 1 female) with a small deletion of a chromosome harbouring genes implicated in hereditary nonpolyposis colorectal cancer (2p, 3p, 7p) who also had IDs and developed colon cancer, 2 of them early in life [41][42][43]. For example, a male patient with a mutation in the PMS2 gene was diagnosed with a rectal carcinoma aged 14 years [44], whilst a man with mild to moderate ID due to Williams syndrome and Lynch syndrome (which increases the risk for colon neoplasia) developed a colorectal cancer aged 37 years [45]. In a Danish cohort of 597 women with Turner syndrome, those who presented with mild IDs were found to be at a higher risk of colon cancer compared to women in the general population [46].…”

“…Reports indicate that symptoms in PWIDs are similar to those observed in individuals without IDs: rectal bleeding [36,43,44,48,60,62], diarrhoea [36,48] and abdominal pain [30,39,48,63], with other tumours being discovered early, resulting from investigations for anaemia [41]. One educational paper used 2 case studies to exemplify the difficulties that PWIDs can experience, such as the delay in reported rectal bleeding before medical investigations are undertaken [60].…”

Diagnosis and Management of Multifocal Gliomas

“…However, it increased to 43% if two factors were present, and to 67% in the presence of all three factors [10]. In a case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, mental retardation, colorectal cancer and multifocal anaplastic astrocytoma, a germline mutation of the PMS2 gene was found [13]. In another case of a 46-year-old woman with a history of ductal adenocarcinoma of the breast and a germline BRCA-1 mutation, the patient developed multicentric glioblastoma multiforme [14].…”