Maria Mercedes de Elejalde

Neuroectodermal Melanolysosomal Disease

Publisher Summary This chapter describes neuroectodermal melanolysosomal disease (NEMLD). NEMLD is characterized by abnormal hair color, severe dysfunction of the central nervous system—profound mental, developmental, and behavioral retardation—abnormal intracytoplasmic inclusions in all tissues studied, and abnormally formed melanosomes. The condition appears to be caused by the pleiotropic effects of an autosomal recessive gene in its homozygous state, producing various phenotypic effects in different tissues. The unusual hair color probably results from the melanocytes in the hair bulb producing melanin in the presence of the different substrates. The color of the hair is probably produced by two factors: (1) the distribution of the melanosomes in the hair shaft, and (2) the diffraction, refraction, and absorption of light by both the pigment granules and the hair matrix. Abnormalities of the dopaminergic pathway are known to be associated with an abnormally functioning central nervous system. In NEMLD, the hypomelanized melanosomes in the skin, the lysosomal inclusions in the fibroblasts, and the lymphocytes and bone marrow cells can be considered authophenes. No specific treatment is available for NEMLD. The infants and children require the specialized care appropriate for children with profound mental retardation and cerebral palsy.

Analysis of the human fetal skeleton and organs with xeroradiography

We have used xeroradiography to study normal and abnormal fetuses including some with anencephaly, hydrocephalus, spina bifida, osteogenesis imperfecta (type IV), Jeune syndrome, radial aplasia, thanatophoric dysplasia, and Pena-Shokeir syndrome. Xeroradiography images the lines of ossification and epiphyses in great detail, shows ossification, and reveals abnormalities that alter bone modeling as seen in Jeune syndrome, osteogenesis imperfecta (type IV), and thanatophoric dysplasia. This technique can be used successfully to examine soft tissues and organs. It can also be used in combination with contrast materials to identify the lateral ventricles, the cardiovascular, gastrointestinal, urinary, and respiratory systems, and the cavities (pleural and peritoneal) of the fetal body.

Fetal phenotypic analysis

Phenotypic analysis has been practised in many different ways, the most common being the recognition of normal and abnormal physical and biochemical characteristics and their patterns of inheritance. As different tools became available to analyze the characteristics of individuals the study of the phenotype and consequently of the genotype became more sophisticated. By the mid 1970’s ultrasonography became a major tool in the analysis of human disease, and more recently it has contributed to the analysis of the human fetal phenotype in utero. This method, when used in conjunction with cytogenetic and biochemical analysis of the amniotic fluid, constitutes the main thrust of genetic prenatal diagnosis today. This paper describes and proposes the systematic use of ultrasonography, in conjunction with biochemical and cytogenetic tests to examine pregnancies at risk of congenital and inherited diseases and those that show signs of abnormality. We have examined 1500 fetuses and have detected conditions that affect only one system, like the skeletal dysplasias (osteogenesis imperfecta, thanatophoric dysplasia, diastrophic dwarfism, achondrogenesis I, Jeune syndrome and many others), neural tube defects, gastroschisis, multiple congenital malformations syndromes (Vater, Vacterl, Weyers olygodactyly, Meckel syndrome, and others). The analysis of the functionality of the fetus is one of the major achievements of genetic prenatal diagnosis by ultrasonography.

Determination of the H-Y antigen in amniotic cells. Its use in prenatal diagnosis.

SummaryThis paper describes the determination of the H-Y antigen in cells obtained from amniotic fluids of two male and two female fetuses found to be normal at birth, and from another fetus that was suspected to have a karyotype 46,XY,t(15;Y) by Q banding. Since the area of the Y chromosome where the H-Y antigen gene appears to be located on the chromosomal material was suspected to be involved in the translocation, it was thought that this fetus could have a double dose of H-Y antigen as seen in 47,XYY individuals. The fetus was found to have a normal dose of the antigen and a normal 46,XY karyotype. The extra material on chromosome 15 was found to be NOR (nuclear organizer region) and to be present in his fathers karyotype. The possibility of this determination in other inherited conditions is discussed.The normal H-Y antigen was an important element in the counseling of this family and helped to rule out the suspected chromosome abnormality. The determination of H-Y antigen is shown to be reliable and simple in amniotic cells, both cultured and directly obtained from the fluid. Its determination appears to be useful in the prenatal determination of other conditions like campomelic dysplasia and Swyers syndrome.