中枢神経系奇形の成立機序と遺伝

Malformations of the Central Nervous System, on Processes of their Manifestations and Inheritance

I．はじめに

　中枢神経系奇形とよばれる異常は，通常先天奇形で，胎生期中にすでにその形成が発足した奇形を指し，分娩時脳の循環障害の結果組織欠損をおこして成立する脳性麻痺や，その原因がすでに遺伝性に決定されている血液不適合による核黄疸の結果などは除外されている。ここに扱う中枢神経系の先天奇形はその異常形態形成が器官形成期である胎生早期の胚とよばれる発生段階に発し，あるいは起源をもつ直接中枢神経系の発生障害または頭蓋骨や椎骨などに関係ある部分の発生障害によつてもたらされた異常にかぎり，胎生期の発生障害ではあつてもトキソプラズマ罹患症，水頭症の一部，灰白質の分化障害などは扱わないことにした。著者に与えられた標題は「奇形性神経疾患の発生，奇形を中心とした遺伝」であるが，内容としては同一であるから表記のように標題を変えた。

　中枢神経系は個体発生において最初に分化する器官で，その分化の速度は発生初期においてはきわめて急速で，かつ哺乳動物とくにヒトにおける中枢神経系の分化は高度，複雑であるため，いろいろの要因によりその正常な分化が妨げられ，発生障害におちいり，結果として先天奇形となることがある。一般に分化の速度が大きい器官ほど発生障害のおこる可能性も大きいことが知られている。したがつて中枢神経系の先天奇形の頻度はいろいろの先天奇形のうちでも高い。

The central nervous system is founded in a very early stage of development compared with other organ systems. The process of development of this system is rapid and complicated. Therefore, it tends to lead to various kinds of developmental dis-turbances. Usually, the malformations are included in the category of disorders of the central nervous system in a wide sense. Malformations of the cen-tral nervous system are caused by two different factors: the one by intrinsic and the other by ext-rinsic factors.

Genetic factors resulted from mutations which occu re in germ cells. Such gene mutations are trans-mitted from the preceding generations. Recently, however, the significance of the effect of extrinsic factors has been noticed. The result of such harm-ful influences upon embryos are usually much severer when the agent affect the embryos during the early stage of development. The stage of deve-lopment at which some extrinsic factors affects the embryos have a greater influence on the type and frequency of malformations than the kind of agent, though the effect of external agents differ from agent to agent. These facts are called stage agent specificity. There is also a third characteristic. It isthe strain or species specificity. Such strain or species specificity is originated from the genetic consititution of the animal. Each organ anlage, for instance, every part of the nervous system, has its own characteristicsensible stage for harmful extrin-sic factors.

Further, the author discussed on mechanisms of manifestions and the inheritance of each individual malformation of the central nervous system.

There are two groups of malformations of the central nervous system. The one iincludes thoseresulted from the failure of the closure of the nerual tube. Anencephalia, spina bifida including spinal dysraphism, congenital syringlmyelia, hydro-myelia, malformations of the cerebellum are exa-mples. The other group consists of those are start-ing after the closure of the nerual tube such as, malformations belonging to univentricular telence-phalon—cyclopia, arrhinencephalia, and otoce-phalia— , malformations in telencephalons with bilateral ventricles, i.e., microcephalia, hydrocepha-lus etc.