KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed.

Background Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity‐related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG). Methods Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene. Results Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four. Conclusion This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait‐based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation.

Background The underlying contributors to cardiovascular disease (CVD) in patients with head and neck squamous cell carcinoma (HNSCC) are poorly characterized. Methods Patients with HNSCC who underwent definitive or adjuvant (chemo)radiation between 2011-2013 were retrospectively reviewed. 10-year risk estimates for a CVD event were calculated according to the Framingham Risk Score (FRS). Results 115 patients with predominantly stage III/IV HNSCC had a median follow-up of two years. At diagnosis, 23% of patients had CVD. The FRS was higher among patients with laryngeal cancer versus other sites (20.5% versus 14.4%). 24% of all patients had uncontrolled blood pressure at diagnosis. Among patients with CVD, 41% were not taking anti-platelet therapy and 30% were not taking statin therapy. 34% of patients without CVD had indications for initiating statin therapy. Conclusions Patients with HNSCC have a high baseline CVD risk and many do not receive optimal preventive care.

Changes in stimulated and non-stimulated whole saliva flow rates were measured in 11 Hodgkin's disease patients who received therapeutic doses of radiation to a mantle field at the M. D. Anderson Hospital in Houston, Texas. Salivary flow rates were examined before, during, and after radiotherapy. Mean flow rate reductions of 54% for non-stimulated saliva and 55.7% for paraffin-stimulated saliva were observed post-radiotherapy. Flow rates had not returned to pre-irradiation levels in any of the patients who were observed for two to three months after completion of therapy. Results obtained from this preliminary study indicate that most patients who receive therapeutic doses of radiation to a mantle field experience a significant reduction in salivary output which is manifest during the period of treatment and persists for a period of at least two to three months post-radiotherapy.