Comparison of different methods of erythrocyte dysmorphism analysis to determine the origin of hematuria

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diagnosis of Smith-Lemli-Opitz syndrome by ultraviolet spectrophotometry

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder due to an inborn error of cholesterol metabolism, characterized by congenital malformations, dysmorphism of multiple organs, mental retardation and delayed neuropsychomotor development resulting from cholesterol biosynthesis deficiency. A defect in 3ß-hydroxysteroid-delta7-reductase (delta7-sterol-reductase), responsible for the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol, causes an increase in 7-DHC and frequently reduces plasma cholesterol levels. The clinical diagnosis of SLOS cannot always be conclusive because of the remarkable variability of clinical expression of the disorder. Thus, confirmation by the measurement of plasma 7-DHC levels is needed. In the present study, we used a simple, fast, and selective method based on ultraviolet spectrophotometry to measure 7-DHC in order to diagnose SLOS. 7-DHC was extracted serially from 200 µl plasma with ethanol and n-hexane and the absorbance at 234 and 282 nm was determined. The method was applied to negative control plasma samples from 23 normal individuals and from 6 cases of suspected SLOS. The method was adequate and reliable and 2 SLOS cases were diagnosed.

Hydrocephalus and moderate mental retardation in a boy with Van der Woude phenotype and IRF6 gene mutation

In this report, we present a boy with lower lip pits, distinct craniofacial dysmorphism with cleft lip and palate, central nervous system malformation, and severe mental retardation. Similar but less pronounced facial findings were present in his mentally normal mother and maternal grandfather, both presenting with lower lip pits. Cleft lip was present in patient's father. Analysis of the VWS1 and VWS2 regions were performed to elucidate the molecular basis of the phenotype of the propositus. Screening or mutations at the IRF6 gene detected a pathogenic mutation (c.960G > C) in the propositus and in his mother; and a single nucleotide polymorphism (c.175-5C > G) in the propositus and in his father. Clinical and genetic aspects of this case are discussed.

GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology

Background: The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.Methods: A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.Results: Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist- treated groups (P > 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P > 0.05).Conclusions: Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.

Gorlin-Goltz Syndrome and Neoplasms: A Case Study

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms', such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. Objective: To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Mild ribs as well as mandibular and maxillar OKC were also diagnosed. Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations and malignant neoplasias.

Correlação entre os dismorfismos oocitários e os resultados da fertilização in vitro

In assisted reproduction, the selection of gametes to achieve better clinical outcomes is a crucial task of embryologists. The quality of the oocyte is a key factor in female fertility, reflecting the intrinsic potential of gamete development, and has a vital role not only in conception but also in subsequent embryonic development. Oocyte dysmorphisms are classified into two types: cytoplasmic, including the presence of granules and/or cytoplasmic inclusions (vacuoles, refractive bodies, and aggregates of the endoplasmic reticulum), and extracytoplasmic (changes in the shape of the oocyte, the zona pellucida, the space perivitelline changes and the polar body). Variations in oocyte morphology may occur due to factors such as the age of women, genetic problems and changes in the hormonal environment to which the oocyte is exposed in ovarian hyperstimulation. The classification of oocyte morphology and its correlation with embryo development and pregnancy rates are controversial in the literature. Several studies show no association between oocyte dysmorphisms and the results of in vitro fertilization, while others report an association between oocyte morphology and embryo development. These differences in the results can be explained by the use of different morphological criteria due to a lack of standardization of oocyte evaluation. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Assessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a genetic disorder characterized by physical and intellectual developmental delay, associated with congenital heart disease and facial dysmorphism. WBS is caused by a microdeletion on chromosome 7 (7q11.23), which encompasses the elastin (ELN) gene and about 27 other genes. The gold standard for WBS laboratory diagnosis is FISH (fluorescence in situ hybridization), which is very costly. As a possible alternative, we investigated the accuracy of three clinical diagnostic scoring systems in 250 patients with WBS diagnosed by FISH. We concluded that all three systems could be used for the clinical diagnosis of WBS, but they all gave a low percentage of false-positive (6.0-9.2%) and false-negative (0.8-4.0%) results. Therefore, their use should be associated with FISH testing. © FUNPEC-RP.

Agonista versus antagonista do GnRH em ciclos de reprodução assistida: morfologia oocitária

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Correlação da maturação e da morfologia do oócito humano com as características do fuso meiótico e da zona pelúcida

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB