Dermatoglyphic findings in 21 probands with cerebral gigantism (Sotos' syndrome) and in their parents and siblings (13 fathers, 18 mothers, 5 brothers, and 12 sisters) were compared with those in normal children (60 boys and 50 girls) to make a contribution to the elucidation of the etiology of cerebral gigantism. The followings were found to be characteristic for probands with cerebral gigantism. 1) The A line terminated at the base of the thumb. 2) Palmar alignment tended to be vertical. 3) The incidence of the third interdigital pattern was high. 4) Increased a-b ridge count was observed. 5) The high frequency of digital whorl pattern was noticed. 6) The total finger ridge count was increased. 7) The incidence of vestiges in thenar areas was high. 8) The incidences of ulnar arch, ulnar loop, and open field loop in hypothenar areas were high. The analysis on family members revealed the fact that they shared a part of the characteristics listed above; that is, the items 1), 2), 7), and 8) were significantly frequent in fathers, items 1), 2), 4), 5), 6), and a part of 8) in mothers, items 3), 6), 7), and 8) in brothers, and items 1), 2), 5), 6) and a part of 8) in sisters. A review of literature revealed 13 pedigrees in which a familial aggregation of cerebral gigantism patients was demonstrated. On the basis of the data here presented, the author concluded that a genetic factor might be involved in the eiology of this syndrome.

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Suckling mice were injected with 30 mg/Kg body weight of cytosine arabinoside subcutaneously 2, 3 and 4 days after birth. In the developing cerebellum, the germinal cells in the external granular layer were selectively destroyed by this procedure. About seven days later, a new external granular layer began to regenerate. Cell proliferation kinetics in the regenerating external granular layer was studied using 3H-thymidine autoradiography. Generation time of germinal cells in the external granular layer was about 1 7.8 hours in the treated mice and 1 9.5 hours in the control at 7 days of age. Thus the generation time was shortened about 1.7 hours in the treated mice. At 13 days of age, the generation time was 17.8 hours in the treated mice and 20.5 hours in the control, thus showing 2.7 hours shortening in the treated. These results indicate that a few germinal cells, which were freed from necrosis caused by cytosine arabinoside, proliferate more rapidly for regeneration.

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Serial sections of microphthalmic chick embryos were examined histologically. Specimens used were from the malformed chick embryos described in the previous report (Kitoh et al. 1978). The examination revealed that the microphthalmias observed in the chick embryos could be classified into two groups, based upon the extent of their abnormalities. The group I microphhtalmia possessed ocular structures which had remained from the early developmental stage. The neural retinae and optic nerves were not formed. In the unilateral microphthalmia of group I, the lens was observed as an encapsulated small spherical body consisting of round cells, without lens fibers. This type of lens seemed to derive from the pigment epithelium. Pigment epithelial cells may thus have migrated first toward the cornea, then were encapsulated and finally lost their pigment granules while being transformed into the lens. On the other hand, the bilateral microphthalmia of group I possessed a rudimentary lens which appeared to be derived from subsiding corneal epithelium. Group II microphthalmia consisted of cases in which the optic cups were formed and the neural retina was differentiated. However, many abnormal ocular structures were noted. The neural retina had irregularly shaped foldings and gave rise to a rosette-formation. In many cases, retinal cysts were formed from the everted retina, caused by incomplete closure of the choroid fissure. The optic nerve was not always formed. In many cases, the lens fused with the cornea, which had a thickened fibrous layer and no endothelium. The lens fibers shownd degeneration in the form of swelling or vacuolation.

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This report describes unexpected induction of paraparesis by IDPN in rats, which paraparesis occured secondary to lordosis of the vertebral column instead of proximal axonopathy. Eighteen pregnant rats were given IDPN in drinking water (approximately 40-70mg/kg/day) from day I through 21 of gestation. Of 15 litters (137 pups) about 50% of newborns died after birth. The survivors did not show any sign of waltzing syndrome characteristic of IDPN poisoning in adult rats. Hindlimb paraparesis developed in 7 of the survivors which became noticeable 3 to 6 weeks after birth. X-ray study revealed subluxation and A-P angulation of the thoracic vertebral column at the T1 to T3 level; most striking was lack of fibrosis around the transected cord. Serial sections of resin-embedded spinal cord revealed no corticospinal tract degeneration and anterior motor neurons of the lumbosacral cord appear normal. Histochemistry on biopsied muscle failed to reveale any signs of neurogenic atrophy in hindlimb muscles. The result suggest that lower motor neurons and motor units develop normally without supra-spinal control if the spinal cord is transected before or around weanling in rats as previously reported by Stelznner et al. No proximal axonopathy ensued and the effects were considered to be those of BAPN (β-aminopropionitrile), the monomer of IDPN, which might have passed through placental barrier.

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The primordial germ cells (PGCs) in amniota originate in the yolk sac endoderm and eventually migrate to the gonadal anlage through the tissue or the blood vessel (in birds). In humans, the PGCs separated from the endoderm migrate through the dorsal mesentery, and the peak of their migration is at the 5th week of embryonic development. The PGC in the migrating phase was irregularly shaped in an amoeboid fashion, suggesting active migration of the cell. Scanning electron microscopy revealed such an amoeboid appearance of the PGC in a three dimensional feature. Evidence for the active movement of the human PGCs in vitro: The PGCs isolated from 5-6 week human embryos were cultured in a plastic dish filled with the L-15 medium and human umbilical cord serum at 35℃. Collagenous fiber nets reconstructed in the culture dish were used as a three dimensional substrate. The PGC was observed moving actively in the substrate. The direction of PGC-locomotion seemed to be at random. The velocity of the locomotion was approximately 30 μm/hr. The PGC in the resting phase was rounded and measured 20 pm in diarneter. When moving, the cell extrernely elongated and measured 90 μm in the longer axis of the cell. In birds, the PGCS being freed from the endoderm temporally circulate through the blood vascular system, leave the circulation and reach the gonadal anlage. Demonstrating of the PGCs escaping from the blood vessel in the chick: In the chick embryo at 2.5 days of incubation, many PGCs were ultrastructurally found escaping from the capillaries in the area between the splanchnopleure and the open gut endoderm, protruding pseudopods through the interendothelial gap of the capillary wall.

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The advantages and disadvantages of studying congenital anomalies in thc Japanese are discussed. The advantages include: 1) the genetically homogenous, large population of Japan; 2) the high consanguinity rate in the Japanese (although it is rapidly decreasing); 3) the uniform, hair, eye and skin color that makes it easy to detect diseases with pigmentation anomalies ; and 4) the gene pool of the Japanese considerably different from that of whites.

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A large number of observations have led us to hypothesize a sequence of causal events in the pathogenesis of preaxial polydactyly in rodents. The two main features are delay in physiological cell death in the preaxial AER which leads to absence of physiological necrosis in the deep preaxial mesoderm ('fpp'). There can be little doubt that these changes in physiological cell death occur and they provide a rational explanation for the paradoxical situation of antiproliferative, cytotoxic drugs producing tissue excess deformities. However the effects of delayed physiological cell death on limb development are totally inferential and it is imperative that direct experimental support be acquired for these postulated effects.

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Primordial germ cells (PGCs) in amphibians were defined and characterized by light and electron microscopy. The process of PGC formation in the South African clawed toad, Xenopus laevis, was explained relative to developmental behavior of the germinal plasm. Experiments demonstrating roles of the germinal plasm in PGC formation in anurans were reviewed, and the contribution of our studies was considered in this context. It has been reported that the animal pole cytoplasm inhibits PGC formation in Xenopus when injected into the vegetal pole region of UV-irradiated or unirradiated intact eggs, thus throwing some doubt on the exclusive role of the germinal plasm in PGC determination. In addition. PGC formation from the presumptive somatic cells was discussed based on data in urodeles. Two different theories underlying the studies of PGC formation were revealed. One is designated as 'determinant' theory, the other induction theory. The former, favorable in anurans, proposes that the presumptive PGCs contain the germinal determinant factors, while cells lacking these factors are differentiated into the somatic cells. The latter, favorable in urodeles, indicates that the 'determinant' specific to PGC formation does not exist, instead PGCs differentiate under some inductive influence from the neighboring embryonic tissues. A possible model applicable to PGC formation both in anurans and urodeles was presented. Studies to obtain conclusive evidence for each of the two working hypotheses, the 'determinant' and induction theories, were described.

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The basic embryonic plan of mammals is inherently feminine. The diversion of this plan is carried out by the Y chromosome which directs the embryonic indifferent gonad to organize a testis instead of an ovary. It has been assumed that the Y chromosome contains a determinant that is essential for the development of a testis (testis-determining gene). On the basis of ubiquitous expression and of widespread phylogenetic conservatism, it has been proposed that serologically-defined H-Y antigen is the product of the testis-determining gene. The proposal has been tested on a considerable variety of exceptional individuals whose gonadal sex does not agree with their chromosomal sex. Any individual who posseses testes in spite of the apparent absence of the Y chromosome should express H-Y antigen on his cells. A series of extensive tests performed on such extraordinary individuals yielded no exception from the above expectation. Gonadal cells dissociated from the neonate of mouse and rat reorganize histotypic aggregates in the Moscona-type aggregation experiment. Testicular cells, lysostripped of H-Y antigen, reorganized ovarian follicular aggregates whereas ovarian cells in the presence of H-Y antigen partially reorganized semiferous tubules-like aggregates. Organ culture for 5 days of bovine XX embryonic indifferent gonads in the presence of the H-Y antigen, excreted from Daudi human male Burkitt lymphoma cells, induced very precocious testicular organogenesis. The above clearly support the proposed testis-organizing function of H-Y antigen.

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In the first half of this study attempts have been made to establish a new score which was designated Mullerian-Inhibition Score (M. I. Score) in order to represent quantitatively the grades of regression of the Mullerian duct. The Mullerian-Inhibiting activities expressed as M. I. Score were determined in the testes of fetal rats and in those of fetal and adult pigs by means of organ culture, in which they were cultured for 3 days in close proximity to the primitive Mullerian duct from female rat fetuses. It was revealed that the fetal testes had significantly high M. I. Score. In the latter half of the study, isolation of Mullerian Inhibitor of fetal pig testes was attempted. They were incubated in Eagle's minimum essential medium. The medium was collected, concentrated using a collodion bag and fractionated on a Sephadex G-200 column. The fractions with molecular weight in the range between 190,000 and 280,000 had specifically high M. I. Score.

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Among the 8,000 fetuses subjected to autopsy by the Department of Pathology, Nagasaki University from 1947 to 1972 and the Department of Geneticopathology, Research Institute for Nuclear Medicine and Biology, Hiroshima University from 1962 to the present, 5,973 cases were picked out as their familial histories, clinical records and autopsy specimens were known. Then the cases with anomalies were selected from those 5,973 cases and analized. The anomalies totaled 1,573 cases (26.3%) in all and the anomalies of urogenital and sexual organs mounted to 425 cases or 27% of the total number of anomalies. These cases have been collected at random from the various medical institutions in the community. They also include those who died right after birth and the stillborn babies sent to us to find out the causes for death. Therefore the frequency of anomalies is more or less higher, yet, they are considered to include various kinds of anomalies impartially. The associated anomalies of urogenital system mounted to 94 cases (22%) out of 425, and if seen in terms of sexuality, 264 male cases (62.1%) predominated 139 female cases (32.7%). In some cases of urogenital anomalies caused by the autosomal recessive type, the autosomal dominant type anomalies and/or the multifactorial inheritance anomalies were found in some other organs. This means that some cases of these anomalies are caused by these "multicausal" factors.

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Sex differentiation is induced by differentiation of undifferentiated form found both in male and female fetuses, Undifferentiated gonad develops into testis or ovary by the action of sex chromosome and hormones secreted from the testis induce differentiation of undifferentiated internal-and external genitalia into male form. The differentiation of external genitalia into male and female types has been shown to be produced only by the presence and absence of androgen in the fetus, respectively. Therefore, absence of androgen action on undifferentiated external genitalia in male fetus and the presence of androgen action in female fetus result in congenital abnormality of external genitalia. Feminization of external genitalia in male fetus is found in those lacking enzymes for the synthesis of testosterone in the testis and in those lacking androgen responsiveness (androgen receptor defect-testicular feminization) in androgen-target cells. Masculinization of external genitalia in female fetus is observed in those secreting large amount of androgens from the fetal adrenal cortex (deficiency of enzymes requiring for the synthesis of cortisol-congenital adrenal hyperplasia).

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Generally, congenital anomalies are defined as developmental abnormalities originating during the embryonic and fetal periods. Therefore, the term congenital anomalies may include the following patterns of abnormalities (genotype or phenocopy) which are caused by genes, or chromosomal, environmental or other unknown factors ; death of embryos and fetuses, congenital malformations, developmental retardations, impairment of functions and intelligence, reproductive disorders, liability, shortening of life span, tumor development and inborn errors of metabolism. There is a close interactive relationship among some of these abnormalities. "A11 congenital malformations are congenital anomalies, but not all anomalies are malformations" (Warkany). The term congenital malformations implies a primary morphologlcal defect that results from developmental errors of morphogenesis, regardless of etiology. These may be macroscopic or microscopic; external or internal ; single or multiple. The types of defects depend on morphogenic characteristic of organ systems, i. e. symmetrical or asymmetrical and parenchymatous or tubular organs. In 1975, comments concerning classification and nomenclature of morphologic defects were proposed by an International Committee held at the National Institute of Health in Bethesda, U. S. A. At present there is no universally accepted nomenclature and classification for congenital malformations. The present report constitutes an effort to standardize those of congenital anomalies from a general teratological point of view.

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Diagnosis of congenital anomalies of the central nervous system has been made easily since the introduction of computed tomography. Clinical diagnosis of congenital anomalies must include determination of their treatablity and prognosis. For the management of congenital anomalies of the central nervous system, investigators should have standardized classification and criteria for their diagnosis. Classification of congenital anomalies of the central nervous system has usually been made by formative pathogenesis. From the clinical standpoint, classification based on developmental stage and causual pathogenesis is more useful. For this purpose, the classification advocated by Dr. DeMyer may fulfil the criterion. This classification is a dendrogram consisting of disorders in three stages; cytogenesis, histogenesis and organogenesis. Disorder of genes presents as metabolic abnormalities and does not show cerebral malformations. Disorder of chromosomes usually shows mental defects and microcephaly without obvious cerebral malformations. Disorder of histogenesis represented by neurocutaneous syndrome does not reveal malformations either. Since stages of development of the central nervous system are long in duration, from early stage of formation of the neural tube to the perinatal period, disorder of organogenesis develops various types of cerebral malformation. In general, the earlier the disorder occurs, the more severe is the malformation. In the present communication, discussion is made to lead to standardization of nomenclature of malformations of the central nervous system.

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External malformations includes diverse anomalies. Here, congenital limb malformations are considered as examples of external malformations. There are various classification systems for limb malformations. For hand malformations, Swanson's classification is widely used in Japan. This classification bases on pathogenesis of hand malformations. However, pathogenetic processes are still unknown for many of hand malformations. It may be worth trying to classify limb malfonnations according to hypothetical pathogenetic processes for research purposes. For clinical description, however, a classification system by anatomical features is preferable. The important point is to preserve the details of the actual event for data storage and retrieval. A descriptive system devised for this purpose by Martinez Frias et al. (Teratology, 15: 163, 1977) is worth mentioning here. In this system, all anomalies are classified into three basic types: excess, deficiency, and fusion. The anatomical structure of the affected limb is defined within a two dimensional order: seven segments in the proximo-distal dimension, and eight rays in the preaxial-postaxial dimension. Classification by this system may seem complicated for nonspecialists, but it has advantages; it can be stored and processed in a computer, and be translated into conventional terminology. At present, storage of precise anatomical data is most important to establish a logical and practical classification system for congenital malformations.

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The term "bone dysplasias", or "constitutional diseases of bone" is used as a general term for congenital and generalized morphological and/or structural bone diseases that are caused by some failures of morphogenesis, growth or maturation of bone and/or cartilage. Most of bone dysplasias are genetic diseases. Pathogenesis of bone dysplasias is considered to be some congenital metabolic failures of bone and cartilage, but is still unknown except in few dysplasias. In 1964, Rubin advocated a dynamic classification of bone dysplasias. He considered that bone dysplasias were caused by hypoplasia or hyperplasia of anatomico-physiological function of tubular bones which he divided in 4- sections: epiphysis, physis, metaphysis and diaphysis. His classification was really unique and was easily accepted by many researchers. Since that time, however, many new dysplasias have been clarified as definite entities. In order to classify these new diseases, a draft of international nomenclature of bone dysplasias was published in 1970. Final draft of international nomenclature was published in 1978. Main purpose of this nomenclature is to standardize the criteria for diagnosis and to report under the same name all over the world. Japanese researchers must also be well acquainted with this nomenclature and have to report cases of bone dysplasias to international medical journals in English so as to join international research net-work.

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While various classification systems have been proposed, only a few have found wide epidemiological and clinical acceptance. The classification of face anomalies proposed in this symposium was basically based on the SNOP and further subclassification according to severity and external or internal malformations was added. Severity of anomalies was devided into two groups, i. e. major and minor anomalies. Each anomaly was introduced into coding system according to classification of developmental mechanisms cited in SNOP coding manual. However, the anomalies which are developed by unknown mechanism were classified into additional item, as special organ anomaly, and the item, hyperplasia or excessive growth was added. Proposed classification was not completely satisfactory, but it was considered to be a relatively suitable for the epidemiological, or pathological or clinical statistics.

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A nomenclature must be clear, unambiguous, accurate and computer-processable. A new nomenclature system is growing by Anderson, Macartney, Shinebourne, Tynan et al. in London. They rejects an embryo-logical standpoint and use only a morphological description. They separate "connection", "relation" and "morphologry" each other. The system is based on a segmental approach A "connection" means concordant, discordant, double inlet, double outlet, etc. A "relation" means left, right, superior, inferior, anterior, posterior, etc. A ventricle is devided into 3 portions, i. e. inlet, trabecular and outlet. When a muscular structure separating a semilunar valve from outlet portion exists, it is called the infundibular septum. When a muscular structure separating a semilunar valve from an atrioventricular valve exists, it is called the ventriculo-infundibular fold. They do not use "conus" or "crista" because those bring a confusion. A ventricle (having inlet and trabecular portions), a rudimentary chamber (outlet chamber and trabecular pouch), and an univentricular heart (a heart having a rudimentary chamber) are defined. A transposition of great arteries is described as "ventriculo-arterial discordance", and a tricuspid arterial is described as "univentricular heart of left ventricular type with absent right atrioventricular connection". An insight into the continuity between various cardiac anomalies seems to be prompted by this nomenclature system.

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The committee of medical terminology in Japanese Association of Pediatric Surgeons has made tremendous works concerning about the medical terms of the pediatric surgical disease. I would like to pick up a few terms about congenital malformations of the abdominal organs. 1. Hirschsprung's disease. This disorder is known as ultrashort segment-, short segment-, intermediate segment-, long segment- and extensive aganglionosis, according to the length of aganglionosis, where, however, designation was different in each reporter. The new proporsal by the committee shows the most accurate term such as aganglionosis of lower rectum (or rectosigmoid, beyond rectosigmoid etc.) according to the extent of aganglionosis. 2. Gastroschisis and intrauterine rupture of omphalocele In 1953, Moore reported that gastroschisis was the malformation of the abdominal wall and it was entirely different from omphalocele which was defined an anomaly of the umbilical cord. There, however, are several discussions about this opinion and I would like to mention my own opinion that astroschisis is intrauterine rupture of the base of the umbilical cord.

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Urogenital organs are classified into the following two groups and fifteen subgroups: Group A, kidney and urinary tract: 1. kidney, 2. calyx and pelvis, 3. UPJ, 4. ureter, 5. UVJ, 6. bladder, 7. trigone and bladder neck, 8. urethra and meatus. Group B, gonad and genital tract: 1. testis, 2. epididymis, 3. seminal duct, 4. seminal vesicle, 5. prostate, 6. penis, 7. scrotum. Their congenital abnormalties may be classified into the following four groups: I. Number; agenesis or aplasia (congenital defect), dupli- or multiplication. II. Position; ectopia, ectopic opening of meatus, malrotation, torsion, transposition. III. Form and structure; fusion, obstructive uropathy, submucous fibrosis, cystic disease. IV. Function; neurogenic dysfunction of urinary tract, hormonal dysfunction of testis. Some abnormalities may belong to several groups in overlap. For example, a fused kidney may be accompanied by the abnormality of number and position of the ureter; renal hypoplasia or dysplasia is often found in case of the ectopic opening of the ureter; bladder exstrophy and epispadias always coexist; testicular agenesis or dysgenesis gives rise to the transformation of internal sexual organs to female type. It is also well known that many congenital abnormalities of urogenital organs, e. g., cryptorchidism, small penis, fused kidney, duplicated renal pelvis and ureter, are often found in various malformation syndromes, e. g., 4p^-, 13-, 18- and 24-trisomies, prune-belly, PradderWilli and crocodile tear syndromes. Congenital abnormalities of urogenital organs are also found frequently in association with simple malformations such as polydactyly and dysplasia of auricle.

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