H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome.

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4-year-old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545.4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease-causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4-associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.

Healthy weight, health behaviours and quality of life among Aboriginal children living in regional Victoria.

OBJECTIVE: To report the prevalence of healthy weight and related behaviours among Victorian Aboriginal and non-Aboriginal children and explore associations between these factors and health-related quality of life (HRQoL). METHODS: Analysis of cross-sectional data from two cluster randomised controlled trials using logistic and linear mixed models. The sample included Aboriginal (n=303) and non-Aboriginal (n=3,026) children aged 8-13 years. RESULTS: More than two-thirds of Aboriginal children met guidelines for fruit (75.9%), sweetened drinks (66.7%), sleep (73.1%), screen time (67.7%) and objectively measured physical activity (83.6%); and 79.1% reported consuming take-away foods less than once per week. Aboriginal children were more likely to meet vegetable consumption guidelines (OR=1.42, 95%CI: 1.05, 1.93), but less likely to have a healthy weight (OR=0.66, 95%CI: 0.52, 0.85) than non-Aboriginal children. Mean HRQoL scores were significantly higher among non-Aboriginal children and both Aboriginal and non-Aboriginal children meeting health guidelines. CONCLUSIONS: Most Aboriginal children in this study met guidelines for fruit, physical activity, screen time and sleep, and those meeting these guidelines had significantly higher HRQoL. IMPLICATIONS FOR PUBLIC HEALTH: Promoting nutrition, physical activity and sleep is likely to benefit all children. Aboriginal community-controlled organisations can use these data to design culturally-specific programs that may improve disparities in healthy weight and HRQoL.

Marijuana use and perinatal outcomes in obstetric patients at a safety net hospital.

OBJECTIVE: To characterize the association between antepartum marijuana exposure and maternal and neonatal outcomes at our institution. STUDY DESIGN: Retrospective chart review identified an obstetric cohort of singleton gestations. Women with self-reported marijuana use were compared with non-users. Demographic characteristics, risk factors, and maternal-fetal outcomes were evaluated. Associations between outcomes and marijuana use were assessed with regression analysis. RESULTS: Of 2792 deliveries, 5.4% reported marijuana use. Compared to non-users, marijuana users entered prenatal care later, were younger, non-Hispanic, and used other illicit substances. Marijuana users had a higher rate of cesarean delivery (p = 0.01). After adjusting for confounders, marijuana use remained associated with 4.1-fold risk of delivering a small for gestational age (SGA) infant and 2.89-fold risk of neonatal oxygen use. CONCLUSION: At a safety net hospital, antepartum marijuana use is significantly associated with cesarean delivery, SGA and supplemental oxygen use at birth. Healthcare disparities associated with marijuana use make this a population of critical interest.

Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). PROCEDURES: Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. RESULTS: Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.

Measurement of Shoulder Abduction Angles in Dogs: An Ex Vivo Study of Accuracy and Repeatability.

OBJECTIVE: The aim of this study was to determine the accuracy and repeatability of the shoulder abduction test and to assess the effect of transection of the medial shoulder support structures in canine cadavers. MATERIALS AND METHODS: The shoulder abduction angle was measured by three separate observers, both with the shoulder extended and at a neutral angle. Shoulder abduction was then measured, using craniocaudal fluoroscopic images. Arthroscopy was performed in all shoulder joints, with the medial support structures transected in one shoulder of each dog. The three observers again measured shoulder abduction angles in all dogs. Shoulder abduction was measured again using fluoroscopy. Accuracy and repeatability of the abduction test were assessed using linear mixed models. RESULTS: All three observers had different measured abduction angles when compared with fluoroscopy (p < 0.01); however, the experienced surgeon had an error of only 2.9°. Inter-observer repeatability was poor, with all three observers having different abduction measurements (p < 0.001). Intra-observer repeatability, however, indicated no differences on repeated measurements (p = 0.26). Placing the shoulder at a neutral standing angle, and transection of support structures caused an average increase in abduction by 8.2° (p < 0.001) and 4.4° respectively. CONCLUSION: Significant variation exists between observers performing this test, increased accuracy seen in the more experienced observer. Shoulder flexion angle can significantly affect measured abduction angles.