CARDIAC MAWORMATIONS IN A/J MICE INWCED BY PHENY?OIN Ali R Fazel, Kathleen K. Sulik, Gerald C. Goerin er, 1201 and ~&mur 1. Hepner, (Spm.by Val Abbssi) . Zrge- town Universitv School of Medicirie, De-ts of Anatow and - - Pediatrics, washington, D. C. fie fetal hydantoin syrkkmr? is characterized by unusual facies, increased incidence of cleft lip (CL) and/or palate, hypplasia of the distal phalanges and an increased incidence of cardiac defects. fie purpose of this s t d y was to identify phenytoin as a cardiac teratogen in A/J mice and to identify the prbrdial cardiac structures affected. At 11 a.m. of gestational day 10, mothers of A/J mice were injected intraperitoneally with 75 mg/kg of phenytoin. Dnbryos, 24, 48, and 72 hours after such treatmmt, and newbm mice were sacrificed as were controls. The spech~ns were fixed i n glutaraldehyde and dissected the following day. They were dehydrated in alcohol and dried by the critical pint technique. fie hearts were sputter coated with gold and examined with a scanning electron microscope a t 20kv. 89/107 offspring of treated mothers had CL as conpared with 8/135 controls.49/89 we cyanotic a t birth. 47 newbms had a patent ductus arterio- sus. 44 had an ostium p r h atrial septa1 defect, 11 with an associated cleft in the anterior mitral leaflet and 7 with clefts in the mitral and triscupid valves. Cbarctation of the aorta was noted i n 11/49 newborn mice. In conclusion, phenytoin can be embryopathic when the embryo is expsed during critical stages of developwnt of the heart and facial processes. ABNORMAL GENITALIA IN MALES WITH SILVER-RUSSELL (SR) 1202 DWARFISM: A NOT INFREQUENT COMPLICATION. Gardner, David 0. Hakanson, Hans Hartenste%%niJo- se h T. L a n m m mf;stateMedicamnter, Dept. of Pea= JL- - 3 - iatrics, Syracuse. The patient to be described weighed 1210 gm at birth, with estimated (Dubowitz) gestation of 38 weeks. The mother had con- genital hydrocol pos, hydronephrosis and bicornuate uterus. Length was 37 cm; head circumference 30 cm. There were hypogly- cemia and thrombocytopenia in the neonatal period. The face was triangular, with the appearance of a large head and small chin, typical for SR dwarfism. The phallus was 2 cm long and was part- ially concealed by a rostra1 investment of scrota1 folds. Testes were palpable bilaterally in the canals. Karyotype was 46,XY. Voiding cystourethrogram revealed a urethra with male configurat- ion, as well as a 9 mn hypoplastic vagina posterior to the ureth- ra. This is consistent with failure of Mullerian inhibiting fac- tor to function in fetal 1ife. Several patients with the SR syn- drome have been found to have obstructive abnormalities of the GU system (Pediatrics 51:216, 1973). At 8 month follow-up the scrotum was almost flat, with only one testis barely palpable in the right canal. Literature review on both sexes with the SR syndrome revealed that 28% of documented cases were males with abnormal genitalia. Several reports described adequate mascul in- ization a t puberty. The latter finding is important to bear in mind when consideration is given to the possibility of assign- ing a female gender role if the penis i s small. =sity of Bashington School of Medic In order to study the effects of varying levels of alcohol consumption during pregnancy, a group of 1,529 unselected mothers were interviewed during their 5th month of pregnancy as to their use of alcohol. At birth, 82 of the infants born to drinking mothers were examined by a dymrphologist, along with 81 con- trols (J Pediatr 92:457, 1978). In the current study, 75 of these infants were re-examined at 4 years, along with 130 child- ren from the same study population. All exams were conducted without knowledge of the mothers' drinking history. Reported alcohol consumption during the month prior to recognition of pregnancy among mothers fromthe experimental group averaged 2.0 oz. absolute alcohol per day, while controls drank infrequently o r never. 2% of the experimental group showed alterations of growth and mrphogenesis ccmpatible with some fetal alcohol effect, compared with of controls (p = .027). There was an increasing incidence of recognizable alcohol effects with in- creasing alcohol consumption (p = .013). Of 11 children judged to show alcohol effects at birth, 10 of these were re-examined at age 4 years, and 8 were independently judged t o show fetal al- cohol effects; their mean IQ was 92. These data suggest that moderate alcohol consumption during pregnancy may result in spec- ific lasting phenotypic alterations which can pennit valid, reli- able judgnents as to the presence of fetal alcohol effects. 1ZU4 INSEETIONS. John M. Graham ' Jr. ' Trent D. Stephens Joseph R. Siebert, David W.'~knitL, ~ymrpholo-it, Division of H~rman Embrvolow. Dents. of Pediatrics and Patholoav. -- . univ, of Yiaskington, skattik: Recent studies suggest that muscle originates frm smites and tendons from lateral plate mesoderm. This study explored the factors which normally determine the location and insertion of a muscle, a previously unanswered question. Human experiments of nature with early problens in morphogenesis were used to deter- mine how muscle developnent proceeds when known critical develop- mental factors are varied. In a variety of monozygotic con- joined twins for whom there could be no genetic determinants for muscle attachnents at the sites of juncture, these attackments must follow general principles of mrphogenesis. A second type involves absence of bone that antedated muscle and tendon devel- opnent (e.g. radial aplasia). A third category includes mechan- ical alteration of early limb position prior to developnent of muscle attachments (e.g. early amnion rupture sequence). The dissection findings f r m all Y types strongly imply a general hi- erarchy of muscle tendon attachments. Tendons appear t o attach preferentially to bone. If the bone they wuld normally attach to is absent, they will attach to the next closest bone. If no such bone is available, they will attach to tendons,' and if no tendon is available, occasionally they will attach to the ap- neurosis of another muscle. If there is no connective tissue attachment site, there will be no muscle, implying a need for function in the developnent and preservation of muscle. THE STILLBORN INFANT: NEED FOR PEDIATRIC CONSULTA- 1205 TION. Jurgen Herrmann, Sean Phipps, and Robert F. Koebert. The Medical College of Wisconsin and Milwaukee Children's Hospital, Department of Pediatrics, Milwaukee, WI. About 1 percent of pregnancies result in a stillborn infant. Thorough obstetric - pathologic - pediatric/genetic evaluation of 37 stillbirths showed a multitude of causes: maternal pre- existing disorders (5%), maternal disorders of pregnancy (5%), disorders of placenta and fetal membranes (lo%), umbilical cord abnormality (3%), fetal abnormalities (49%), and instances of sudden fetal death syndrome without specifically determined cause (27%). Frequently (76%) the cause was not obstetric and often (43%) it was not apparent from postmortem examination. Since the pathologic findings, where noted, generally related to fetal rather than to maternal ab~ormalities,the obstetrician may not be adept at delineating all the possible implications important for parental understanding and acceptance of the event, future obstetric management, recurrence risk determination, and se- lection of prenatal diagnostic procedures during future preg- nancies. We recommend that obstetricians involve pediatricians (who may have to be better trained in this areal) as consultants to help determine the cause and implications of the event. ACROMESOMELIC DYSPLASIA, A HISTOCHEMICAL STUDY OF THE 1206 ENDOCHONRAL GROWTH PLAm, William A. Horton, Arthur S Aylsworth, (sponsored by R. Neil Schimke), University of Kansas School of Medicine, Departments of Pediatrics and Medi- cine, Kansas City; University of North Carolina, Department of Pe . diatrics, &ape1 Hill. Endochondral growth plate cartilage from a patient with the typical clinical and radiographic features of acromesomelic dys- plasia was studied histochemically and innnunohistochemically. The investigation revealed many previously undescribed abnormalities. The cartilage was hypercellular in general. fiere were numerous small areas of matrix degeneration scattered through the resting zone avd a few large islands of hypertrophic cartilage in the growth plate region. Staining indicated excessive amounts of chondroitin sulfate and an absence of collagen fibers in both of these areas. In the remaining cartilage, collagen fibers tended to aggregate around the cells. The resting chondrocytes were ir- regular in size and distribution, and many exhibited protein con- taining cytoplasmic inclusions. The growth plate per se was poorly organized; hypertrophic chondrocytes were randomly orient- ed. The provisional calcification of cartilage matrix was ab- sent, but the mineralization of subchondral bone appeared normal except along the outer margin where bone formation extended into the perichondrial space. These abnormalities appear to be dis- tinct for acromesomelic dysplasia. Moreover, they provide sev- eral clues regarding the pathogenesis of the disorder.