Rome is certainly one of the places in the world which speaks to us of twins more than any other, and, in Rome itself, the Capitoline Hall of the Horatii and Guriatii triplets. From the myth of Romulus and Remus, history gradually passes through the tale of the triplets from Rome and Albalonga, who prevented a bigger war, up to the memory of the Emperor-philosopher Marcus Aurelius, who had twin sons.

Today, however, not only legend and history deal with twins, but also science and particularly demography and genetics do so as well.

Demography discovers constants in the frequency of the phenomenon of twins, and this presents characteristic variabilities which aid in reconstructing the ethnological events of the human species. The example of Italy is characteristic (see sketch on the cover of the book).

Genetics has found in twins a special motif of interest, in that about one-third of the twins are identical, that is, they have the same hereditary patrimony. On the basis of this phenomenon, twins hereditarily different are also utilized, and special study methods have been set up. The study of twins today opens up in a special way a new field of Genetics, of which they represent the most important and demonstrative test: the heredity of biological time, or Chronogenetics.

The association of hereditary spino-ponto-cerebellar degenerations with tapetoretinal degenerations of varying types, and particularly with Stargardt's macular degeneration, is not rare, as at the present time more than 200 cases are known. Therefore the one-gene hypothesis seems to be the most plausible. The fact that there exist complex neuroophthalmological forms near purely neurological or purely retinal forms, is also in favour of one gene with polyphenic manifestation.

The clinical findings in a group of syndromes in which tapetoretinal degenerations are associated with systemic lipid disorders are described. This group includes abetalipoproteinemia (the syndrome of Bassen and Kornzweig), Refsum's syndrome, Neuronal Ceroid Lipofuscinosis, and Cockayne's syndrome. AII four are transmitted by single autosomal recessive genes. The pathological findings are discussed. If diagnosed early enough, abetalipoproteinemia should be treated by administration of vitamin A, and Refsum's syndrome by restriction of intake of phytanic acid and phytol.

Inherited tapetoretinal degenerations associated with, or caused by, abnormalities in lipid metabolism are discussed in terms of recent findings regarding their etiology. The biochemical basis of these tapetoretinal degenerations may be summarized as follows.

(a) In abetalipoproteinemia (the Bassen-Kornzweig syndrome) there is a complete absence of all plasma lipoproteins except HDL (alfalipoprotein; high density lipoprotein). In addition the levels of plasma lipids, including vitamin A, are grossly dimished. The genetically-caused basic defect in this disorder is the absence of a specific protein component, apoLP-ser, in the plasma lipoproteins.

(b) In a milder form of hypobetalipoproteinemia, transmitted as an autosomal dominant trait, there is little, if any, retinal degeneration.

(c) Refsum's syndrome is characterized by greatly increased plasma levels of phytanic acid, a 20-carbon branched-chain fatty acid. This substance is not synthesized in the body, but originates from dietary sources only. Patients with Refsum's syndrome lack the enzyme (phytanic acid oxidase) necessary to oxidize this fatty acid, and its accumulation in the tissues has severe consequences. Therapeutic measures, consisting of restriction of dietary phytanic acid, have given encouraging results.

(d) Three forms of Batten's disease (neuronal ceroid lipofuscinosis) are now recognized. These are (1) the rapidly progressive (Jansky-Bielschowsky) form, (2) the chronic (Batten-Mayou-Vogt-Spielmeyer-Sjögren) form, which is the most common, and (3) the late onset (Kufs') form. All are associated — to varying degrees — with an accumulation of autofluorescent ceroidlipofuscin pigments. The enzymatic defect is believed to consist of abnormalities in peroxidase enzymes.

(e) Other tapetoretinal degenerations thought to be associated with defects in lipid metabolism are discussed briefly. These include Hooffs disease, Cockayne's syndrome, and Alstrom's syndrome.

A study has been made of 35 patients belonging to 20 families, all diagnosed as Usher's syndrome (retinitis pigmentosa and deafness). The results indicate that there are four clinical types, which have been called Types I to IV. Genetically, they represent at least two, and possibly three or four, separate entities.

This review deals with CNS troubles and anomalies (excluding mental defects and oligophrenia, as well as primary muscular degenerations), that account for approximately 25 percent of all cases of genetic counseling in our material.

From a genetic-counseling perspective, CNS affections may be easily classed as follows: (1) congenital malformations; (2) monofactorial Mendelian affections; (3) diseases with a possibly hereditary disposition (e.g., arthrogryposis); (4) infant cerebral palsies; and (5) epilepsies.

In our own material, CNS congenital malformations account for approximately 60 percent of all cases of neurologic genetic counseling, whereas Mendelian affections account for only 20 percent and epilepsies for 15 percent. They mainly include cases of hydrocephaly, anencephaly, spina bifida, and microcephaly, for which the recurrence risk is mostly empirical. Emphasis is laid on the present possibilities of prenatal detection of some of these malformations.

On the basis of their genetic-counseling experience with 4000 propositi, the authors start by recalling in a first part the fundamental mechanisms of the appearance and heritability of chromosomal aberrations.

In a second part, they summarize the correlations between clinical cases and chromosomal abnormalities presently described in the literature. Only the syndromes in which a neurologic and/or an ophthalmologic history exists are reported.

In a third part, modalities of genetic counseling, with a summing-up of general risks for chromosomal rearrangements and of their principal circumstances of diagnosis, are related.

Genealogic and cytogenetic studies necessary for counseling are briefly recorded.

Prenatal diagnosis, although it has been introduced only a few years ago, has already become an important branch of genetics and cytogenetics.

Metabolites of certain monogenic diseases can be discovered in the supernatant of the amniotic fluid, although reliable results are obtained in later months of pregnancy only.

Determination of fetal sex is important if the mother is a proven carrier of a severe X-linked disease such as X-linked muscular dystrophies, Hunter's, Lowe's, Lesch-Nyhan disease. It can be done by the analysis of nuclear sex or sex chromosomal complement.

Biochemical studies of amniotic fluid cells, notably cultured amniotic fluid cells, permit prenatal diagnosis of some inborn errors of metabolism such as Tay-Sachs disease, Hurler's and Hunter's disease, and some rare monogenic diseases.

Numerically of greater importance is the prenatal chromosomal analysis of high-risk women. Provided it could be done in all so-called high-risk women, a considerable number of aneuploidies could be prenatally detected and ultimately prevented.

Religious and legal implications of eugenic abortions are discussed.

The geneticist faced with severe neuroophthalmological conditions should not only establish the prognosis on the basis of probability laws, but also take into consideration the prevailing affective and social situation of these patients and their families.

Huntington's chorea, e.g., manifests itself between 30 and 40 years of age, that is to say, when the patients often have already one or more children, who shall be exposed to the threat of becoming affected until rather an advanced age.

Among other dominant affections, myotonic dystrophy (Steinert) is discussed, which can nowadays be diagnosed in about 1/3 of cases before the first clinical manifestations, owing to slit-lamp examination and electromyography. Contrary to Huntington's disease, the affection can be detected at an early stage of life, so that the patients may still be dissuaded from having children.

In the field of ophthalmological conditions, the genetics of uni- and bilateral retinoblastoma, the three types of retinitis pigmentosa (recessive, dominant, sex-linked), the Lowe's and Waardenburg-Klein syndromes, as well as Tay-Sachs disease, are reviewed. As regards the latter condition, the importance of the discovery of a deficiency of hexosaminidase A is pointed out, since the detection of heterozygous carriers, and even prenatal diagnosis, have now become possible for this disease.

In the central nervous system, besides the neurotransmitters, the occurrence of substances which modify neuronal excitability has been proposed. Since their effect is a matter of modulating neuronal responsiveness, these substances may be called neuromodulators.

Examples of neurotransmitters or putative neurotransmitters in the central nervous system are acetylcholine, noradrenaline, dopamine, and aminoacids such as GABA, glycine, and L-glutamic acid. Under certain conditions, some of these (acetylcholine, L-glutamic acid, and GABA), as well as hormones and polypeptides (e.g., releasing factors) are considered to act as neuromodulators.