1. The incidence of chromosomal aberration with CHD is 10.5% in the autopsy cases. 2. The characteristic major cardiac malformations associated with chromosomal aberration are conal abnormality, abnormal septation and cardiac valve abnormalities. 3. The characteristic association of chromosomal aberration and CHD is CAVO in Down syndrome, triple shunts and multivalvular disease in 18 trisomy, shunts in delition syndrome and coarctation of the aorta in Turner syndrome. 4. Minor cardiac anomalies associated with chromosomal aberration are valve dysplasia such as bicuspid semilunar cusps, parachute A-V valve, thickning, deformity and insufficient differentiation of valve and of chordae tendinae and hypoplastic or immature papillary muscles. 5. Primary target in cardiovascular involvement by chromosomal aberration might be a cement property of the connective tissue which is expected to conseal the foramens and shunts and to develop valve structures in embryonic heart.

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The hereditary QT prolongation syndrome in Japan was reviewed and some genetic analysis was performed with cooperation of doctors who had reported the cases with the syndrome. Pathological findings of the conducting system of my own two cases were demonstrated. Seven cases with Jervell and Lange-Nielsen syndrome were reported in Japan. Although no consanguineous marriage was evident in any cases, the autosomal recessive inheritance was suggested. An incidence of 5 among 1336 deaf-mute pupils was obtained by two epidemiological surveys. Twenty-eight families with Romano-Ward syndrome in Japan were collected according to the criteria used in this study. One hundred eighty-nine individuals (69 males and 120 females) of 28 families who belong to the affected kindreds were examined with electrocardiograms and history taking. These were 120 affected (63.5%) among 189 cases, 6 with QT prolongation, syncopal attack, and sudden death, 40 with QT prolongation an syncopal attack, and 74 with QT prolongation only. Penetrance of the character form affected parents to his (her) offspring was calculated to be about 100%, supporting the concept that the inheritance of Romano-Ward syndrome is a simple autosomal dominance. On the other hand, penetrance of the character from affected individuals or sibships to their parents was calculated to be a little less than 90%, suggesting that some of affected cases might lose the character of Romano-Ward syndrome as they grow older. Segregation analysis also supported an autosomal dominant inheritance. Definite sex difference was found in Romano-Ward syndrome in two aspects. One was observed in the incidence of the affected individuals. Twenty-nine (42.0%) of 69 males were affected, while 91 (75.8%) of 120 females. Furthermore, among 28 probands, 26 were female and only 2 were male. Another sex difference was found in the expressivity or in the severity of the clinical features. Extent of QT prolongation was much more marked in the females than in the males. Most male cases developed their first syncopal attack before the age of 15, while more than half of the females at of after the age of 15 years, again demonstrating sex difference in Romano-Ward syndrome. In the two autopsied cases marked enlargement and degeneration of the ventricular Purkinje cells were observed which could be responsible for QT prolongation, the abnormality of the repolarization process somewhere in the ventricle.

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The further selection of stroke-prone spontaneously hypertensive rats (SHR) by the grade of hypertension resulted in the separation of substrains with more and less severe hypertension, respectively. Their average tail blood pressures at the age of 100 days were 240 and 200 mmHg. The ratios of cerebral hemorrhage to infarction were markedly decreased from 1/2 in the former into less than 1/30 in the latter. Also a similar attempt separated stroke-resistant SHR into substrains with moderate and mild hypertension; blood pressures at the age of 100 days were 200 and 180 mmHg, respectively. On the other hand, development of severe hypertension was attenuated and the incidence of stroke was significantly reduced in stroke-prone SHR when they were fed on a high-fet-cholesterol diet or a high fish protein diet. The selection of substrains with different grades of hypertension in stroke-prone and stroke-resistant SHR indicates the additional involvement of some hypertension genes, and the alteration of the course and the level of hypertension by nutritional factors substantiates the importance of gene-environment interaction in spontaneous hypertension.

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The authors carried out blood pressure investigations in different parts and over long periods to make an analysis of the inheritance of essential hypertension from various aspects. The results obtained, including many already reported by the authors as wel as those reported by other investigators and analyzed by the authors, may be systematically summarized as follows: 1) Essential hypertension is a polygenic disease governed by polygenic systems. 2) The heritability of the disease is estimated at about 50%, indicating that inheritance and environment are of equal importance as factors for its appearance. 3) The number of gene loci (N), the effect of a gene (α), and the frequency of a positive gene (q) were estimated at N=13 to 15, α=4 to 8, and q=0.50, respectively. 4) The correlation between the variation of blood pressure distribution with an increase in age and the action of polygenes was analysed genetically by setting up models, with the result suggesting the variation in the variance of gene effect to be strongly influenced by an increase in age. 5) Juvenile and non-juvenile hypertension were analyzed for their genetic correlation to suggest that they may be governed not by different gene groups, but by pleiotropism at least. 6) A method has been devised by which the reciprocal action between the genotype and environment responsible for essential hypertension can be estimated from data for monozygotic twins, and by this method the reciprocal action between genotype and environment was estimated to give a piece of information of importance. We are afraid that some of the foregoing estimates may not necessarily be representative of the general population tested because of the limited number of cases examined. Further investigations under a longterm program for estimates of higher accuracy are believed to contribute much to clinical genetics.

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Genetic analyses of 565 first-degree relatives of 99 patients with ICM suggests that ICM has both simple dominant and recessive modes of inheritance. There was no clinical form of ICM specific to the mode of inheritance, both hypertrophic and congestive types almost equally observed both modes of inheritance. Two pairs of identical twins who suggested the simple recessive mode were reported.

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