Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis.

Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the PIEZO1 gene diagnosed prenatally using exome sequencing (ES). Two variants in PIEZO1 (c.3206G>A and c.6208A>C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the PIEZO1 subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review PIEZO1 variants as a cause of GLD and discuss the uses of prenatal ES to date.

Pharmacy Implementation of a New Law Allowing Year-Long Hormonal Contraception Supplies.

BACKGROUND: Prescription hormonal contraceptive methods are vital to prevention of unplanned pregnancies. New legislation among 23 states has expanded access to contraception. In California, a 2017 law requires pharmacists to dispense year-long supplies of contraception and insurance plans to cover it upon patients' request. This study assesses pharmacist knowledge of this new law 6 months after enactment. METHODS: From July to November 2017, a random selection of 600 community pharmacies were called requesting a pharmacist (n = 532, 88.7% response). Pharmacists were asked if they had heard of the new law, if they would dispense a year-long supply to cash-pay, privately or publicly insured patients, and what they perceived as obstacles to dispensing year-long supplies. RESULTS: Awareness of this law was assessed through these surveys. Most pharmacists responded they would dispense year-long supplies to cash-pay patients, regardless of knowledge of the new law (81% of "knew", 70% of "did not know", p = 0.1046). The top two perceived obstacles were insurance reimbursement (55.8%) and store policy (13.4%). CONCLUSION: Despite a new law requiring insurance coverage of a year-long supply of prescription birth control, most pharmacists were unaware at six months after the policy went into effect. Of those who were aware, the majority did not clearly understand it. Compliance among insurance plans is unknown. There was no implementation plan or awareness campaign for the new law.