Antenatal diagnosis of placenta accreta spectrum (PAS) disorders.

Antenatal diagnosis of placenta accreta spectrum (PAS) disorders allows planned management by a multidisciplinary team in a tertiary center, and thus can reduce hemorrhagic morbidity, compared with intrapartum diagnosis. Previous Cesarean section and placenta previa are the two most common risk factors. Prenatal ultrasound is a promising diagnostic tool for PAS in the second or third trimester. Recent evidence shows sonographic markers of PAS can be present in the first trimester. Prenatal ultrasound may help predict the depth and topography of placental invasion which are the major determinants of maternal morbidity. The presence of increased vascularity in the inferior part of the lower uterine segment and the parametrial region is associated with a more severe disorder according to a newly proposed staging system. In this chapter, we will discuss how to improve the prediction of PAS, the depth, and topography of placental invasion.

The KLHL40 c.1516A>C is a Chinese-specific founder mutation causing nemaline myopathy 8: Report of six patients with pre- and postnatal phenotypes.

BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.