The frequency of genetic eye diseases in a genetic counseling center.

The frequency of genetic eye diseases in a genetic counseling center: In this study the incidence of eye diseases of genetic origin in patients attending our genetic counseling center for a period of almost six years is documented. The frequency of retinitis pigmentosa, congenital cataracts, lens dislocation, microphthalmos, retinoblastoma, congenital glaucoma, congenital ptosis, degenerative myopia, strabismus, optic atrophy, various genetic metabolic diseases have been investigated, and the results are presented. Preventive approaches and prenatal diagnostic possibilities are discussed and the importance of genetic counseling is emphasized.

[What should the pediatrician know about prenatal AFP diagnosis?]. / Was sollte der Pädiater über die pränatale AFP-Diagnostik wissen?

Alphafetoprotein (AFP) represents an embryo-fetal glycoprotein. The fetus it enters amnion fluid and maternal serum. Increased concentrations are observed in these fluids in the presence of certain fetal malformations, e.g. neural tube defects and anterior abdominal wall defects or omphalocele, and in congenital nephrosis of the Finnish type. An increased concentration also signals general risks as an increased tendency to abortion or to low birth weight infants. Very low maternal serum AFP indicates an increased risk for trisomy 21. Postnatally increased AFP-concentration has been described in ataxia-teleangiectasia (Louis-Bar-Syndrome) and in severe combined immunodeficiency syndrome. Although the AFP-determination is mainly used for obstetric prenatal care and diagnosis it also has an importance for the pediatrician as an early indicator of special risks.

[Important progress for the ophthalmologist in basic genetic research]. / Für den Augenarzt wichtige Fortschritte der genetischen Grundlagenforschung.

Ophthalmologists and human geneticists share a long standing interest in hereditary diseases and anomalies of the eye. Many of the primary genetic eye diseases are known, as ophthalmic symptoms are frequently part of a pleiotropic gene effect or the eye is affected secondarily. Progress in human genetics has also improved the understanding of genetic eye diseases. This can be demonstrated in the analysis of the function of color-vision genes and their abnormalities as well as the retinoblastoma gene. A line can be drawn from early formal analysis of pedigrees to cytogenetic mapping and, finally DNA analysis and sequencing of the involved genes. These advances have not only led to theoretical insights but also have practical applications where the determination of risk is concerned or prenatal diagnosis, genetic counselling, preventive measures and guidance. The retinoblastoma gene has become an important model for a tumor suppressor gene and tumorigenesis in general. Its influence on other types of tumors, such as osteosarcoma and breast cancer must be clarified. Sequencing of the gene opens the possibility of reconstructing the primary gene product by "reverse genetics" and of analyzing its mode of action. DNA analysis has been extended to an increasing number of eye diseases. Precise clinical and genetic analysis and diagnosis are of primary importance, however, for progress in this field.

[Progress in prenatal diagnosis]. / Fortschritte der Pränataldiagnostik.

Prenatal diagnosis is primarily the task of the obstetrician and clinical geneticist, but it must concern the pediatrician as well. It may give advance warning of postnatal problems and yield information that is valuable in the care of the newborn. Moreover, the pediatrician may be called upon to judge the prognosis of a child with a prenatally detected anomaly and prenatal therapy might be considered. Recent progress in prenatal diagnosis concerns sonography, including fetal blood sampling and biopsy; early detection of neural tube defects by alpha-fetoprotein and acetylcholinesterase determination (ACHE test); first trimester diagnosis of chromosome anomalies and inborn errors of metabolism; and prenatal DNA analysis. Technical progress in prenatal diagnosis improves the reliability of prognosis and genetic counselling, but also adds to existing ethical problems and may create new ones.

[Human genetics. Clinical and preventive aspects from the viewpoint of obstetrics and gynecology]. / Humangenetik. Klinik und Vorsorge unter dem Aspekt der Geburtshilfe und Gynäkologie

Clinical genetics and genetic counselling can be applied effectively only, if close cooperation is secured between the clinical geneticist and the physician in the field. The limited capacity of all institutes of human genetics makes it mandatory that general practicioners and the various specialists preselect patients for special genetic work-up and counselling. Quite often it is their obligation also to secure and document findings, prerequisite for effective genetic counselling, which would be lost otherwise. Special points are discussed and illustrated with typical cases.

[Prenatal recognition of genetic diseases and neural tube defects]. / Pränatale Erfassung von Erbleiden und Neuralrohr-defekten.

A growing number of metabolic genetic defects can be diagnosed prenatally; however, the most common genetic diseases defy our efforts so far. Promising new avenues are mentioned. Efforts to diagnose neural tube defects in early pregnancy have gained wide acceptance. The most widely used method is alpha-fetoprotein (AFP)-determination in amnion fluid supplemented by ultrasound examination and particularly successfully by the ACHE-(acetyl-cholinesterase)gel test. In many countries, a general introduction of AFP-screening in maternal serum for neural tube defects is being considered. Two large field studies, each including some 24,000 patients, will soon be completed in Giessen and Hannover. They were designed to supplement the data from Great Britain in judging the advisability of mass screening of maternal serum AFP in the second trimenon in a low-incidence area such as Western Germany. The concluding discussion touches on future aspects of prenatal diagnosis and ethical considerations.

[Fetoscopy (author's transl)]. / Die Fetoskopie.

It is the aim of fetoscopy to recognise or exclude malformations which are visible in the fetal stage and which are not associated with chromosomal damage. The requisite endoscope can be inserted practically without any problems into the amniotic cavity under local anaesthesia and in the manner of an "extended amniocentesis". If pregnancy is continued, the risk involed in fetoscopy must be assessed as similarly low as that of simple aminocentesis, as the clinical experience collected so far has shown. The clinical use of fetoscopy requires close co-operation with the geneticist and the parents concerned. The decision that fetoscopy is indicated lies mainly with the geneticist on account of the required expert genetic knowledge. Fetoscopy appears justified if there is an increased risk of malformation of the fetus which is manifest in the foetal stage and which is sufficiently serious to initiate therapeutic abortion if necessary, and, furthermore, if the risk involved in fetoscopy is in reasonable proportion to the risk of teh malformation. Over and above this, fetoscopy can also be justified if it is necessary to obtain fetal blood for examination. Satisfactory technical and endoscopic experience is the most important prerequisite for success and for reduced risk. Up to now, indication of fetoscopy was exclusively coupled to existing pregnancy and enhanced genetic risk. On the other hand, the question whether pregnancy should be permitted despite a known risk, simply because subsequent fetoscopy is envisaged, should be treated with reserve.

Epidemiology of neural tube defects in Germany.

A survey is made of the epidemiologic studies of neural tube defects (NTD) in Germany. A temporary increase is noted in the prevalence of NTD at birth for the time during and shortly after the Second World War, followed by a downward trend thereafter. Thus an earlier observation of Lenz (1965) could be confirmed. Falling rates of NTD were also reported from various other countries in recent years. No convincing etiological explanation is available so far. The current prevalence of NTD at birth can be estimated for Germany to be about 1.0-1.5 per thousand newborns with about an even distribution to anencephalus and spina bifida.

Familial basal cell nevus syndrome.

The basal cell nevus syndrome is characterized by multiple basal cell nevi and basal cell carcinoma, cysts of the jaw, anomalies of ribs and spine, abnormal calcifications, and additional anomalies of the facial skull. A German family is described with manifestations of the syndrome in the mother and her three daughters. Expressivity was variable, in part due to age effects. The observation conforms to the assumed autosomal dominant mode of inheritance with high penetrance.

Sibs of probands with neural tube defects--a study in the Federal Republic of Germany.

Data for the risk of neural tube defects in sibs of affected children are needed for genetic counselling, for decision on prenatal studies, and for planning of preventive measures. Data have been reported from various populations but were lacking for Germany. This study presents data on the siblings of 240 index patients in the Western part of the Federal Republic of Germany. The prevalence among sibs of affected individuals was found to be 2.6%. This figure agrees well with reports from other countries in Continental Europe and the United States, and fits the expectation of lower recurrence risks in low incidence populations.

Fatal aplastic anaemia in a child with features of Dubowitz syndrome.

We describe a boy with features of Dubowitz syndrome who developed anaemia, thrombocytopenia and granulocytopenia at 3 years of age. The family refused blood component transfusion and he died 6 months later from severe anaemia and pulmonary bleeding. This is the second case of bone marrow aplasia in 38 reported cases of Dubowitz syndrome. It is proposed that patients with Dubowitz syndrome need long-term follow up, including complete blood counts.

Spermatogenetic arrest with inhibition of acrosome and sperm tail development.

Testicular biopsies from two brothers with pathologic spermatograms revealed a spermatogenetic arrest at early spermatid maturation. No sign of acrosome or sperm tail formation was found in spermatids. Using a polyclonal antibody against vimentin, Sertoli cells appeared in the normal shape and distribution pattern. At the ultrastructural level no significant pathologic alterations of Sertoli cells were visible. A monoclonal antibody against tubulin gave a diffuse perinuclear reaction in spermatogonia, spermatocytes and spermatids. Some tubulin-immunoreactive material was also present in the apical portions of the Sertoli cells. Ultrastructural studies of spermatids revealed a complete absence of the centrioles and axonemal structures in early spermatids. Acrosome formation was inhibited at the early Golgi stage. The numerous spermatids present within germinal epithelium contained an abundance of elongate mitochondria and membrane profiles surrounding the nucleus. The ultrastructural findings indicate a maturation stop of spermatids at a very early stage with complete inhibition of acrosome and sperm tail formation. The underlying mechanism could be a lack of specific structural proteins.

Maternal serum alpha-fetoprotein screening for neural tube defects. Report of a combined study in Germany and short overview on screening in populations with low birth prevalence of neural tube defects.

The basis of maternal serum alpha-fetoprotein (AFP)-screening for neural tube defects is discussed. A report is given of a large scale screening study in the Federal Republic of Germany combining the experiences in Giessen and Hannover on over 50,000 pregnant women, about evenly distributed among both centers. Published and known forthcoming data from other low incidence populations, particularly of European countries, are reviewed briefly. The conclusion is reached that general screening could effectively be instituted and in the final result should also be cost-beneficial.