Ken-ichi Ohba

Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion 5(p15.1q35.1)

SummaryA male infant with karyotype 46,XY,rec(5),dup q,inv(5)(p15.1 q35.1)pat is presented. The proband showed growth and developmental retardation, complex cardiovascular abnormalities, inguinal hernia and microcephaly in addition to facial appearance and cat-like cry characteristic of the cri-du-chat syndrome. Growth and developmental retardation, and microcephly noted in this patient were markedly more serious than those observed in patients either with partial monosomy 5p or with partial trisomy 5q alone.

Teratogenic Effects of Sodium Valproate in the Jcl: ICR Mouse Fetus

Sodium valproate was administered to Jc1:ICR mice in order to evaluate its teratogenicity. A single dose of 600 mg/kg of sodium valproate was injected intrapentoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized, and live fetuses were inspected for the presence of external and internal abnormalities. Exencephaly and urogenital abnormalities showed the highest frequency in the group treated on day 8, being recognized in about 60% and 10% of live fetuses, respectively. Cardiovascular abnormalities were found in the highest frequency in the group treated on day 7 (in about 30% of live fetuses). Incidence of tail abnormality was found to increase with delay in day of drug administration. Other abnormalities observed were cleft palate and digital malformation. Our study showed that a constellation of major abnormalities similar to the congenital valproate syndrome suspected in humans could be produced in the Jc1:ICR mouse fetus.

Etiologic and Pathogenetic Study of Mental Retardation with Multiple Congenital Anomalies

Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 236 (41.5%) who were involved with MCA.

Association of congenital heart disease, blepharoptosis, and short stature

SummaryWe found 12 patients with congenital heart disease of unknown etiology complicated with blepharoptosis during a period from Sept. 1, 1981 to April 30, 1989. All the patients with congenital heart disease were acyanotic, including 10 with short stature. Among these 10, abnormalities of high frequency were intrauterine growth retardation (5 cases), mental retardation (5), microcephaly (3), epicanthus (4), high arched palate (4), sacral dimple (4), and distal axial triradius (3). It is postulated that the association of congenital heart disease, blepharoptosis and short stature might indicate pathogenetic relationships.

Clinical and Postmortem Findings of Two Cases With Karyotype: 48, XXX, +18

Clinical and postmortem findings of two cases with karyotype: 48, XXX, +18 are presented. In both patients the usual characteristics of trisomy 18 were found. Case 1 was complicated with congenital esophageal atresia, hypoplastic left auricle with external auditory canal atresia, left congenital dislocation of hip, and left club foot. The patient died on the 9th day after birth. Autopsy revealed mitral atresia, aortic stenosis, ventricular septal defect, patent ductus arteriosus, coarctation of aorta, bicuspid aortic and pulmonary valves, patent foramen ovale, and congenital esophageal atresia (type C). Case 2 died on the 8th day after birth. Postmortem examination revealed ventricular septal defect, but there was no other noteworthy malformation. Dermatoglyphic findings were more prominent on the right hand than the left. The severity of malformations may be biased to either the right or the left side.

9p Deletion and distal 9q duplication due to a paternal pericentric inversion 9(p22q32)

SummaryA female infant with 46,XX,rec(9), dup q,inv(9)(p22q32)pat is presented. She had a duplication from 9q32 to qter and a deletion from 9q22 to 9pter. Phenotypical abnormalities observed corresponded with features noted in cases with distal dup (9q), while pathognomonic features of del(9p) syndrome were not observed.

Partial trisomy for 19q due to paternal 17/19 reciprocal translocation

SummaryA malformed female infant having karyotype 46,XX,der(17), t(17;19) (q25.3;q13.3)pat is reported. She had following abnormalities: low birth weight, congenital heart disease, microcephaly, high frontal hairline, short nose with flat nasal root, cleft lip and palate, broad mouth with downturned commissures, short neck with excess skin, clinodactyly of 5th fingers, sacral dimple, wide set nipples, and unilateral palmar transverse crease. Autopsy revealed congenital heart disease and polysplenia, but no abnormality was found in other organs. Her sister was stillborn, with cleft lip and palate. Our case suggests that fatality due to severely malformed internal organs may occur in duplication at the distal third of 19q.

Carbamazepine-Induced Cardiovascular Abnormalities in Chick Embryos

ABSTRACT  Carbamazepine dissolved in propylene glycol was administered to chick embryos in order to determine its teratogenicity in the cardiovascular system. A single dose of 3, 5, 7, or 10 mg was administered at 72 hours of incubation (Hamburger‐Hamilton stage 18). On day 10 of incubation, embryos were removed and examined for cardiovascular abnormalities. Cardiovascular abnormalities were noted in 37.8%, 54.8%, 76.9%, and 88.0% of live embryos in groups treated with 3, 5, 7, and 10 mg, respectively. Our experiment represented a statistically significant increase of cardiovascular abnormalities and showed a significant dose‐dependent increase. Infundibular ventricular septa1 defect was the primary cardiac anomaly observed in this study. A high percentage of this anomaly was accompanied by hypoplastic right 6th aortic arch artery and/or persistent left 4th aortic arch artery. A small number of double outlet right ventricle was found.

Sodium Valproate‐lnduced Cardiovascular Abnormalities in the JchlCR Mouse Fetus

Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.

Familial X;Y translocation in a malformed male infant and his mother

SummaryA male infant, the proband, with 46,Y,der(X),t(X;Y)(p22.3; q11.1), and his mother with 46,X,der(X),t(X;Y)(q22.3;q11.1) are presented. The proband was involved with a peculiar face, congenital heart disease, dry and scaly skin, and growth and psychomotor retardation. He died on the 111th day after birth. At necropsy a congenital heart disease was found, but there was no other major visceral malformation. The mother of the proband was healthy except for her short stature associated with disproportionately short limbs. Steroid sulfatase activity in her skin fibroblasts and lymphocytes was only half that of normal females.