Homozygous/compound heterozygote RYR1 gene variants: Expanding the clinical spectrum.

The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation-contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next-generation gene sequencing and growing number of causative variants, the spectrum of ryanodinopathies has been evolving with dominant and recessive variants presenting with RYR1-related congenital myopathies such as central core disease, minicore myopathy with external ophthalmoplegia, core-rod myopathy, and congenital neuromuscular disease. Lately, the spectrum was broadened to include fetal manifestations, causing a rare recessive and lethal form of fetal akinesia deformation sequence syndrome (FADS)/arthrogryposis multiplex congenita (AMC) and lethal multiple pterygium syndrome. Here we broaden the spectrum of clinical manifestations associated with homozygous/compound heterozygous RYR1 gene variants to include a wide range of manifestations from FADS through neonatal hypotonia to a 35-year-old male with AMC and PhD degree. We report five unrelated families in which three presented with FADS. One of these families was consanguineous and had three affected fetuses with FADS, one patient with neonatal hypotonia who is alive, and one individual with AMC who is 35 years old with normal intellectual development and uses a wheelchair. Muscle biopsies on these cases demonstrated a variety of histopathological abnormalities, which did not assist with the diagnostic process. Neither the affected living individuals nor the parents who are obligate heterozygotes had history of malignant hyperthermia.

Sexual health knowledge in a vulnerable population: a survey of adolescents in the bateyes of La Romana, Dominican Republic.

OBJECTIVE: Undocumented Haitian migrants to the Dominican Republic often live in impoverished communities called bateyes. These contexts present challenges for adolescent sexual health education. To inform development of appropriate adolescent education programs, this study assessed their general sexual health knowledge. METHODS: A locally developed sexual health knowledge survey was administered to 930 grade 7-12 adolescents attending six batey schools. Analysis of aggregated responses reviewed general demographics (e.g. age and sex), and identified top community sexual health concerns and most trusted information sources. RESULTS: Top concerns included menstruation (25.5%), HIV (21.8%), and family planning (13.3%); stratification by sex identified discordance around menstruation (89.2% female, 10.8% male) and HIV (67.1% male, 32.9% female), but not family planning (47.2% male, 52.8% female). Parents were identified as the most trusted information source, irrespective of concern. CONCLUSION: Community concerns around menstruation matches extant developing-world literature that links menarche with female stigma and school absence. Interest in HIV and family planning suggests targeted promoted efforts would be of benefit. Trust in parents is reflective of cultural traditions and suggests potential knowledge impacts arising from effective parental education.