Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene.

AIMS: A couple were referred for prenatal genetic testing at 31 weeks' gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and a small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. MATERIALS AND METHODS: Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid. RESULTS: A pathogenic homozygous nonsense variant in KLHL7 (NM_001031710.2) associated with PERCHING syndrome (#617055) was identified. CONCLUSION: Whilst there are detailed descriptions of the many postnatal phenotypes seen in these patients, there are few reports of features identified during pregnancy. This report is the first published prenatal diagnosis of PERCHING syndrome and provides further information on the associated fetal phenotypes.

Molecular autopsy by trio exome sequencing (ES) and postmortem examination in fetuses and neonates with prenatally identified structural anomalies.

PURPOSE: To determine the diagnostic yield of combined exome sequencing (ES) and autopsy in fetuses/neonates with prenatally identified structural anomalies resulting in termination of pregnancy, intrauterine, neonatal, or early infant death. METHODS: ES was undertaken in 27 proband/parent trios following full autopsy. Candidate pathogenic variants were classified by a multidisciplinary clinical review panel using American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: A genetic diagnosis was established in ten cases (37%). Pathogenic/likely pathogenic variants were identified in nine different genes including four de novo autosomal dominant, three homozygous autosomal recessive, two compound heterozygous autosomal recessive, and one X-linked. KMT2D variants (associated with Kabuki syndrome postnatally) occurred in two cases. Pathogenic variants were identified in 5/13 (38%) cases with multisystem anomalies, in 2/4 (50%) cases with fetal akinesia deformation sequence, and in 1/4 (25%) cases each with cardiac and brain anomalies and hydrops fetalis. No pathogenic variants were detected in fetuses with genitourinary (1), skeletal (1), or abdominal (1) abnormalities. CONCLUSION: This cohort demonstrates the clinical utility of molecular autopsy with ES to identify an underlying genetic cause in structurally abnormal fetuses/neonates. These molecular findings provided parents with an explanation of the developmental abnormality, delineated the recurrence risks, and assisted the management of subsequent pregnancies.

Identifying Caregiver Needs for Children With a Tracheostomy Living at Home.

This study sought to understand caregiver needs of children with tracheostomies (CWT) living at home and inform development of standardized tracheostomy simulation training curricula. Long-term goals are decreasing hospital readmissions following tracheostomy placement and improving family experiences while implementing a medical home model. We recruited caregivers of CWT and conducted semistructured interviews, subsequently recorded, transcribed, and analyzed for emerging themes using NVivo. Demographic data were collected via quantitative surveys. Twenty-seven caregivers participated. Emerging themes included the following: (1) caregivers felt overwhelmed, sad, frightened when learning need for tracheostomy; (2) training described as adequate, but individualized training desired; (3) families felt prepared to go home, but transition was difficult; (4) home nursing care fraught with difficulty and yet essential for families of CWT. Families of CWT have specific needs related to discharge training, resources, support, and home nursing. Provider understanding of caregiver needs is essential for child well-being, patient-/family-centered care, and may improve health outcomes.

The first antenatal diagnosis of KBG syndrome: a microdeletion at chromosome 16q24.2q24.3 containing multiple genes including ANKRD11 associated with the disorder.

The loss of ANKRD11 gene confirms the diagnosis of KBG syndrome but does not elucidate the pediatric phenotype providing a counseling challenge. With the expansion of prenatal diagnosis, and the potential to perform whole-exome sequencing antenatally, we must describe the genetic abnormalities, antenatal ultrasound findings, and phenotype concurrently to facilitate counseling.

Food security in Nunavut, Canada: barriers and recommendations.

OBJECTIVES: The food supply of Inuit living in Nunavut, Canada, is characterized by market food of relatively low nutritional value and nutrient-dense traditional food. The objective of this study is to assess community perceptions about the availability and accessibility of traditional and market foods in Nunavut. STUDY DESIGN: A qualitative study using focus group methodology. METHODS: Focus groups were conducted in 6 communities in Nunavut in 2004 and collected information was analyzed. RESULTS: Barriers to increased traditional food consumption included high costs of hunting and changes in lifestyle and cultural practices. Participants suggested that food security could be gained through increased economic support for local community hunts, freezers and education programs, as well as better access to cheaper and higher quality market food. CONCLUSIONS: Interventions to improve the dietary quality of Nunavut residents are discussed.

Food Use and Nutrient Adequacy in Baffin Inuit Children and Adolescents.

In evaluating adequacy of nutrient intake and relative contribution of locally harvested food (i.e., "traditional" food) and imported market food for 164 Baffin Inuit children and adolescents, 604 24-hour recalls were obtained over a one-year period (1987 to 1988). Market food contributed an average of 84% of dietary energy and traditional food, 16%. Total and saturated fat intakes corresponded closely to current recommendations, while sucrose intakes were higher than recommended. Most age and gender categories had a low prevalence of inadequate intakes of iron, zinc, and protein; over 50% of dietary iron and zinc was provided by traditional food. Calcium and vitamin A were obtained largely through market food, and there was a high risk of inadequacy for both nutrients in all age groups. The diets of 16-18-year-old girls were the most often inadequate, due to high consumption of low nutrient-dense food and low consumption of traditional food. Food items rich in vitamin A and calcium should be promoted, and 16-18-year-old girls specifically targeted for education on food choices and health.

Healthy living in Nunavut: an on-line nutrition course for inuit communities in the Canadian arctic.

OBJECTIVES: It is recognized that empowerment of Indigenous Peoples through training and education is a priority. The objective was to design a course that would provide an innovative training approach to targeted workers in remote communities and enhance learning related to the Nunavut Food Guide, traditional food and nutrition, and diabetes prevention. STUDY DESIGN: A steering committee was established at the outset of the project with representation from McGill University and the Government of Nunavut (including nutritionists, community nurses and community health representatives (CHRs), as well as with members of the target audience. Course content and implementation, as well as recruitment of the target audience, were carried out with guidance from the steering committee. METHODS: An 8-week long course was developed for delivery in January - March, 2004. Learning activities included presentation of the course content through stories, online self-assessment quizzes, time-independent online discussions and telephone-based discussions. Invitations were extended to all prenatal nutrition program workers, CHRs, CHR students, home-care workers, Aboriginal Diabetes Initiative workers and public health nurses in Nunavut. RESULTS: Ninety-six health-care workers registered for Healthy Living in Nunavut, with 44 actively participating, 23 with less active participation and 29 who did not participate. CONCLUSIONS: Despite having to overcome numerous technological, linguistic and cultural barriers, approximately 40% of registrants actively participated in the online nutrition course. The internet may be a useful medium for delivery of information to target audiences in the North.