Rising incidence of colorectal cancer in individuals younger than 50 years and increasing mortality from rectosigmoid cancer in England.

AIM: The aim was to describe changes in incidence and mortality from colorectal cancer (CRC) in England by analysing data available from the National Cancer Registration and Analysis Service (NCRAS, 2001-2017). METHODS: Data analysis was undertaken to interpret trends and patterns in age-standardized incidence and death rates from CRC, including sub-analyses by six age groups (0-24, 25-49, 50-59, 60-69, 70-79, 80+) and three sites of cancer-colonic, rectosigmoid and rectal. RESULTS: Overall CRC incidence remained relatively stable-70.1 cases per 100 000 individuals (95% CI 69.3-71.0) in 2001 and 68.8 cases (95% CI 68.0-69.5) in 2017. Sub-analysis demonstrates a quarter fewer incidence of rectosigmoid cancer (-27%). This is counterbalanced by a 3% rise in colon cancers. The age-standardized incidence rate of CRC increased by 59% in the 25-49 age group. In the over 50s, CRC incidence remained stable, with reductions seen in rectosigmoid cancer (50-59 years, -19%; 60-69, -26%; 70-79, -39%; 80+, -27%). Overall, mortality improved (-18.7%), primarily as a result of the reduction in deaths from colon (-31.6%) and rectal cancers (-25.1%). Deaths from the small incident number of rectosigmoid cancers, however, demonstrated a significant increase overall (+166.7%). Grouped age-standardized death rate analyses showed increasing death rates in the under 50s (+28.3%) compared to declining rates in the over 50s (-15.8%). CONCLUSIONS: There is a clear trend in increased incidence and mortality in individuals under 50 years old. There is also a trend to increased mortality from rectosigmoid cancer. These findings should have implications for national screening programme extension to under 50s and a call to arms for appropriate identification, staging and treatment of rectosigmoid cancers.

Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.