Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Developmental brain abnormalities are complex and can be difficult to diagnose by prenatal imaging because of the ongoing growth and development of the brain throughout pregnancy and the limitations of ultrasound, often requiring fetal magnetic resonance imaging as an additional tool. As for all major structural congenital anomalies, amniocentesis with chromosomal microarray and a karyotype is the first-line recommended test for the genetic work-up of prenatally diagnosed central nervous system (CNS) abnormalities. Many CNS defects, especially neuronal migration defects affecting the cerebral and cerebellar cortex, are caused by single-gene mutations in a large number of different genes. Early data suggest that prenatal diagnostic exome sequencing for fetal CNS defects will have a high diagnostic yield, but interpretation of sequencing results can be complex. Yet a genetic diagnosis is important for prognosis prediction and recurrence risk counseling. The evaluation and management of such patients is best done in a multidisciplinary team approach. Here, we review general principles of the genetic work-up for fetuses with CNS defects and review categories of genetic causes of prenatally diagnosed CNS phenotypes.     

The formation of dithionate during the iron(III)-catalysed autoxidation of sulfur(IV)-oxides

The iron(III)-catalyzed autoxidation of sulfur(IV)-oxides results in the formation of two different oxidation products of sulfur(IV): dithionate, S₂O₆²⁻, and sulfate, SO₄²⁻. The yield of these reaction products depends on the experimental conditions. Under the studied conditions ([Fe(III)] : [SIV)] = 1:10, pH = 2–4) dithionate is the minor reaction product. The formation of dithionate is influenced by the initial pH but not by the initial O₂ concentration. The presence of CO²⁺, Mn²⁺, and Ni²⁺ have no influence on the yield of dithionate, whereas in the presence of Cr³⁺ less and, in the presence of Cu²⁺, no dithionate is formed.     

Aspects of biopsy procedures prior to preimplantation genetic diagnosis

Today, preimplantation genetic diagnosis (PGD) is offered in over 40 centres worldwide for an expanded range of genetic defects causing disease. This very early form of prenatal diagnosis involves the detection of affected embryos by fluorescent in situ hybridization (FISH) (sex determination or chromosomal defects) or by polymerase chain reaction (PCR) (monogenic diseases) prior to implantation. Genetic analysis of the embryos involves the removal of some cellular mass from the embryos (one or two blastomeres at cleavage-stage or some extra-embryonic trophectoderm cells at the blastocyst stage) by means of an embryo biopsy procedure. Genetic analysis can also be performed preconceptionally by removal of the first polar body. However, additional information is then often gained by removal of the second polar body and/or a blastomere from the embryo. Removal of polar bodies or cellular material from embryos requires an opening in the zona pellucida, which can be created in a mechanical way (partial zona dissection) or chemical way (acidic Tyrode's solution). However, the more recent introduction of laser technology has facilitated this step enormously. Different biopsy procedures at different preimplantation stages are reviewed here, including their pros and cons and their clinical applications. The following aspects will also be discussed: safety of zona drilling by laser, use of Ca²⁺/Mg²⁺-free medium for decompaction, and removal of one or two cells from cleavage-stage embryos. Copyright © 2001 John Wiley & Sons, Ltd.     

Mitigating GHG Emissions in the Humid Tropics: Case Studies from the Alternatives to Slash-and-Burn Program (ASB)

Tropical forest conversion contributes as much as 25% of the net annual CO₂ emissions and up to 10% of the N_2O emissions to the atmosphere. The net effect on global warming potential (GWP) also depends on the net fluxes of greenhouse gases from land-use systems following deforestation. Efforts to mitigate these effects must take into account not only the greenhouse gas fluxes of alternative land-use systems but also the social and economic consequences that influence their widespread adoption. The global alternatives to slash-and-burn program (ASB) investigated the net greenhouse gas emissions and profitability of a range of land-use alternatives in the humid tropics. The analysis showed that many tree-based systems reduced net GWP compared to annual cropping and pasture systems. Some of these systems are also profitable in terms of returns to land and labor. The widespread adoption of these systems, however, can be limited by start-up costs, credit limitations, and number of years to positive cash flow, in addition to the higher labor requirements. Projects that offset carbon emissions through carbon sinks in land use in the tropics might be a means of overcoming these limitations. A synthesis of the findings from this program can provide guidelines for the selection and promotion of land-use practices that minimize net global warming effects of slash-and-burn.     

Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management

Cases where initial prenatal diagnosis was made of isolated unilateral multicystic kidney (UMCK) were reviewed to determine appropriate counselling and management strategies. For the 73 cases, chromosome abnormalities, pregnancy complications and family histories were reviewed. In addition, subsequently diagnosed birth defects, and pediatric medical and surgical outcomes were available for 54 cases. Of those with outcome information available renal/genital–urinary tract abnormalities were diagnosed subsequently in 33% and non-renal abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was present among 32 cases where karyotypes were known (3%). Amniotic fluid volume abnormalities were present in 11 cases but not predictive of associated anomalies, with the exception of one case where polyhydramnios accompanied multiple malformations consistent with VATER association. A family history of structural renal anomalies was reported in 11 cases (20%). There were 14 cases of partial or complete involution (25%), including two cases of complete prenatal involution of the cystic kidneys. No long-term associated morbidity such as hypertension or malignancy was present in our cohort. Based on our study and corroborating literature, amniocentesis should be offered to women when a seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore, a detailed ultrasound with careful assessment of the fetal heart and contralateral kidney is indicated at diagnosis and during the third trimester to assess for further evidence of structural abnormalities, as well as amniotic fluid volume abnormalities. Careful assessment of the newborn is indicated with appropriate speciality referral as required. Copyright © 2002 John Wiley & Sons, Ltd.     

Population Persistence in Florida Torreya: Comparing Modeled Projections of a Declining Coniferous Tree

Abstract: The Florida torreya (   Torreya taxifolia ) is a coniferous tree endemic to a 35-km stretch of bluffs and ravines along the east side of the Apalachicola River in northern Florida and southern Georgia. This formerly locally abundant tree has declined as a result of disease during the 1950s and is on the U.S. endangered species list. With no seed production in the wild, this species is headed toward extinction. We conducted a survey on roughly 200 trees from 1988 to 1996 and used these data to estimate the likelihood of population persistence during the next several decades. We compared a stage-class transition matrix model ( RAMAS) and an individual-based stochastic model ( TORSIM) of growth and mortality to project future populations. Given the current lack of seed production in the wild, all models predict extinction. The question of concern is the imminence of this predicted extinction. Differing predicted times to extinction would suggest different immediate management recommendations. Both models predicted an over 90% likelihood of persistence during the next 50 years. Predictions differed in that the transition matrix model was less optimistic than the individual-based model regarding persistence. Model sensitivity analysis showed that the results were robust to significant decreases in growth and sprouting probabilities. Submodels identified different persistence likelihoods in different populations. Nonetheless, unless management of the population can facilitate maturation and seed production, extinction of this species in the wild is inevitable.