Amniocentesis was developed as a therapeutically-oriented procedure, and still is when performed in the third trimester of pregnancy. But mid-trimester amniocentesis (14th to 18th week) is at present applied only for eugenic reasons: (1) to determine the sex of the baby, (2) to diagnose the presence and nature of a chromosomal disorder, (3) to diagnose an inborn error of metabolism by an appropriate enzyme assay on cells cultured from amniocentesis-obtained fluid.

Since most of the diseases that can be diagnosed in this way are not treatable as yet, antenatal diagnosis is used only to inform the parents and/or facilitate selective abortion of defective babies or carriers. It is obvious that ethical principles must be applied to human acts such as these. These principles applied depend on the philosophical and religious views one brings to bear on such problems.

It is suggested that standards derived from a secular humanist philosophy, such as the ‘good’ of society, familial or parental ‘good’, a ‘natural’ standard such as ‘quality of life’, are all inadequate and indeed dangerous.

The argument is presented that these grave issues can safely be resolved only in an ethical system that is based on optimal value judgements; they will be optimal if they are informed by a sound metaphysics of being, and suffused by the light of a vision of man derived from Divinely-revealed truth as transmitted chiefly by the teaching authority of the Church founded by God.

Among X-linked neuroophthalmological ailments, congenital nystagmus is particularly interesting because of the affected female heterozygote.

Linkage and crossingover with Xg blood group suggest that the locus of the nystagmic gene is on the long arm of the X chromosome.

A draft of genetic counseling is given according to the various possible family situations.

This study involves the presentation of a kindred from Southwestern Louisiana showing 66 individuals who were heterozygous for a rare dominant gene for a type of Charcot-Marie-Tooth disease with hypertrophy of peripheral nerves. Two marriages between heterozygotes resulted in the occurrence of five homozygous offsprings. Clinical features of these previously undescribed homozygotes are compared to the clinical features of the classic type of heterozygote. The value of using nerve-conduction time to detect the asymptomatic heterozygote for Charcot-Marie-Tooth disease is discussed.

Remarkable progress in adapting specific chromosomal and biochemical tests to amniotic fluid samples has allowed intrauterine diagnosis for an increasing number of inherited conditions. However, the lack of any specific tests for autosomal dominant diseases, especially those affecting the nervous system and muscle, has precluded such prenatal evaluation in genetic counseling.

Genetic linkage offers a potentially useful alternative approach to such diseases. The gene for a particular disorder must be closely linked to a genetic marker which can be analyzed in amniotic fluid or cells obtained in the second trimester of pregnancy.

We have recently applied linkage studies to the prediction of myotonic dystrophy (Dm) during pregnancy. Dm is known to be closely linked to the secretor locus (Se), which determines the secretion of ABH blood-group substances into saliva and other body fluids, including the amniotic fluid of the fetus.

Only certain families will be suitable for this analysis: the affected parent must have thesecretor-positive phenotype and be heterozygous (Se/se) at the secretor locus; the coupling of the Dm allele to the Se or se allele must be determined; and the spouse must be either secretor-negative or heterozygous secretor-positive. Secretor genotypes can be inferred from secretor phenotypes of close relatives, including the fetus at risk.

Unfortunately, these criteria will be satisfied in only 5-10 percent of couples at risk to transmit myotonic dystrophy. In suitable couples, however, linkage analysis can be quite helpful.

The identity of an autosomal recessive form of chronic spinal muscular atrophy with clinical features intermediate between acute Werdnig-Hojfmann disease and Kugelberg-Welander disease is confirmed. This form accounts for the majority of patients with spinal muscular atrophy surviving into adult life. Spinal muscular atrophy with onset after 2 years of age is a heterogeneous group and both autosomal recessive and autosomal dominant forms occur.

The cases of neurologic interest of the Mendel Institute's Eugenic Counseling Service and the various counseling possibilities, at a prezygotic, zygotic, and clinical level, are reviewed.

The importance of the data collected and their possibilities of application to the general population are stressed.

On the basis of a research on 100 patients a correlation is shown to exist between myasthenia gravis and HL-A 8.

The findings further support the supposition that myasthenia gravis should be divided into two types, respectively showing an increase of HL-A 8 and an increase of HL-A 2.

A large genetic survey of all infantile and childhood spinal muscular atrophies has been undertaken. Two large series have been studied, one consecutive series of 160 patients presenting to the Hospital for Sick Children, London, and approximately 60 patients from the Muscular-Dystrophy-Group Research Laboratories, Regional Neurological Centre.

Using the techniques of sibling-sibling correlation it has been shown for the first time that the acute fatal infantile form (classical acute Werdnig-Hoffmann disease) is a distinct genetic entity. It is then possible by such genetic techniques to define accurately the clinical syndrome.

Implications for genetic counselling are discussed. Gene frequency studies have been undertaken from this research project and it is now known that the carrier rate for the acute Werdnig-Hoffman disease gene is in the range 1:60 to 1:90 in the British population.

A new syndrome in three siblings, a man and two women, now aged 33-45 years, is described. The syndrome consists of the following symptoms:

1. Oligophrenia (IQ about 30, Terman-Merrill test) with harmonic infantilism.

2. Dense cataract with onset in childhood.

3. Myopathy, mainly affecting proximal muscles but also facial, masticatory, and external ocular muscles. The myopathy probably had its onset at puberty and progressed, in 2 of the 3 siblings until they were confined to a wheel chair.

4. Signs of pyramidal tract involvement and slight ataxia, probably congenital and nonprogressive.

5. Deficient speech development.

6. Skeletal changes including thoracic deformity, scoliosis, pes planovalgus, shortening of the fourth toe, and osseous dystrophy especially in the hands and feet.

7. Hypergonadotropic hypogonadism with primary amenorrhea in one of the sisters, very early menopause in the other and pronounced testicular atrophy in the brother. There were no signs of other endocrine insufficiency and the secondary sex characters, body hair distribution and libido were normal. The karyotype was normal in all three siblings. The heredity was considered to be probably autosomal recessive. Since, therefore, a number of independent organs were affected, the syndrome has been assumed to be caused by a penetrating metabolic defect the nature of which is unknown.

A family is described in which spastic paraplegia and retinal degeneration were observed in 5 out of 11 sibs in one generation. All affected members of this family had the onset of bilateral ocular symptoms during the fourth to fifth decade. Visual impairment was slowly progressive and ranged from 20/25 to 20/100.

There was a macular and perimacular speckling with small, irregular, discrete spots and central pigment proliferation, at the level of the pigment epithelium. Fluorescein angiography revealed patches of proliferating retinal pigment epithelium blocking transmission of fluorescein, surrounded by a larger area of disruption of the retinal pigment epithelium giving a “window-effect” choroidal pattern. The right macula showed a nonspecific, nonfluorescent, reticular pattern.

The most likely explanation of the ocular findings was a retinal degeneration involving the retinal pigment epithelium and/or the chorio-capillaries. Extensive laboratory work was negative.

A case of 8 trisomy syndrome, identified on the basis of the heat denaturation technique, has been detected in a patient with mental retardation, congenital malformations, and peculiar ocular anomalies. This observation confirms that, even without evidence of mosaicism, this chromosome does not seriously upset the viability of cells and could be less deleterious to the individual than trisomy 13, 18, or 21.

The mental development is not too much impaired and the skeletal abnormalities are mild, as compared to those found in previously reported cases. On the other hand, the cardiovascular system is involved and the ocular lesions are complex. They include prominent eyes, epicanthus, hypertelorism, antimongoloid slant of palpebral fissures, ectopia of lacrimal point, megalocornea, enlarged iridocorneal angle, subatrophic papilla, tortuosities of retinal vessels, absence of deep perception.

The case is described of a child who presented a slight psychomotor retardation and malformative signs, together with an XYY caryotype, and who died at the age of 7 years from a medulloblastoma, as could be later confirmed by autoptic examination.

The relations between chromosomal and neoplastic pathology are described.

A total of 105 sibships with one or more members affected by CNS malformations have been drawn from the Mendel Institute's Eugenic Counseling file and examined. The mode of inheritance and the variability of segregation have been verified according to the presence or absence of spina bifida occulta in one or both parents.

The results obtained lead the authors to suggest that the expression of major genes responsible for the pathology be conditioned by minor genes responsible for localization.

The results of a study on the chromosome association index carried out on a sample of singletons and on a sample of MZ and DZ twins, all of different age groups, lead to tentatively conclude that the reduced efficiency of mitotic genotypes, as reflected by the phenomenon of association, is genetically conditioned.

Blast index, mitotic index, and rearrangement index, have been assessed and compared in a sample of male MZ and DZ twin pairs belonging to two age groups: 10 and 60 years. For all three indexes, both the hereditary conditioning and age modifications could thus be confirmed.

A sample of sibships with two or more members affected by progressive muscular dystrophy has been drawn from the Mendel Institute's Eugenic Counseling file and examined with respect to the age of onset of the pathology (its clinical varieties being taken into account) in the members of the same sibship. Significant correlations have been found, thus suggesting the existence of characteristic ages of onset within each family.

A study of weight increase in the first year of life has been carried out on a sample of 50 MZ and 50 DZ twin pairs of both sexes, as compared to a similar sample of singletons. The results show that weight increase, as examined at different stages in the first year of life, undergoes significant hereditary conditioning (H ≃ 0.60).

Following previous application of mathematical models to the study of gene decay, as suggested by Gedda-Brenci's model of the ergon-chronon system, further results are reported, with special respect to a mathematical model of back mutations.

Personal examination of 39 cases of Fabry's disease, with special respect to a chronogenetical analysis, revealed interesting temporal features both in the age of onset and the age of death.

The results of a study based on(1) a sample of 9000 cases of psoriosis, (2) a more specific sample of 2000 patients of psoriasis with one family member also affected, and (3) a small sample of affected twins, lead to the tentative conclusion that disposition to psoriasis may well be the result of a differential time of decay of the genetic information.