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Objective: In an attempt to refine the role of ultrasonography in screening and identifying fetuses at risk for chromosomal abnormalities, a retrospective review of patients undergoing genetic amniocentesis was undertaken.Study Design: Computer databases from the perinatal biology laboratory and cytogenetics laboratory of our institution were correlated to compare the results of the fetus' ultrasonographic examination with the cytogenetic results from amniocentesis. Univariate and multivariate analysis were used to determine the best correlations between ultrasonographic findings and chromosomal abnormalities (study 1). The results were used to construct regression analysis formulas and a Neural Network program to predict the presence or absence of chromosomal abnormalities in a second set of patients (study 2) undergoing genetic amniocentesis.Results: One hundred twenty-five chromosomal abnormalities were found in 3775 fetuses in study 1 (3.3%). Multivariate analysis showed significant correlations between anomalies of the central nervous system, heart, face and neck, and extremities and increased nuchal fold, increased bowel echogenicity, abnormal biparietal diameter-to-femur ratio, and the presence of chromosomal abnormalities. Regression equations and a Neural Network program successfully predicted the presence or absence of fetal chromosomal abnormalities in a second set of 901 at-risk fetuses.Conclusion: A normal ultrasonographic examination result in patients who are at increased risk for fetal chromosomal abnormalities reduces the risk 2- to 3-fold, whereas the presence of any major ultrasonographic abnormality or certain minor abnormalities significantly increases the risk. The application of these results to low-risk patients is still premature. [ABSTRACT FROM AUTHOR]

A 3 1/2-year-old female with clinical features of Down's syndrome was found to have extra chromosome material on the long arm of one of the X chromosomes, 46,XXq+. The parental karyotypes were normal. In the light of the clinical features of the proband an the banding characteristics of the extra chromosome material, the patient was thought to have a de novo (X;21) translocation. The results of late replication studies with BUdR and enzyme superoxide dismutase (SOD) assays in the proband suggest that: (1) the presumed (X;21) translocation chromosome was the late replicating chromosome; (2) the spread of inactivation extended from the Xq segment of the translocation chromosome to the proximal part of the segment derived from chromosome 21, leading to the inactivation of the autosomal gene for enzyme SOD; (3) the remaining distal portion of the (X;21) translocation chromosome, a part of a segment presumably derived from chromosome 21, was spared from the spread of inactivation so that this part was still genetically active and responsible for the Down's phenotype; (4) therefore, the main determinants for a Down's phenotype may be located more distally (q22.2 or q22.3 or both) than the SOD gene (q22.1) on the long arm of chromosome 21. [ABSTRACT FROM PUBLISHER]

Extra chromosomal material on the long arm of chromosome 15 was found in an infant with growth retardation, dysmorphic features, skeletal abnormalities, and congenital heart defect. The phenotypically normal mother had a balanced translocation between the short arm of chromosome 8 and the long arm of chromosome 15: 46,XX,t(8:15)(p12:q25). Thus, the patient was partially trisomic for the short arm of chromosome 8 (p12 leads to pter). Comparison of the clinical data obtained from patients with partial trisomy of the short arm of chromosome 8 with those of full trisomy 8 (Warkany's syndrome) suggests that most of the clinical features of Warkany's syndrome require excess material from both the short and long arm of chromosome 8. [ABSTRACT FROM PUBLISHER]

Several members in two families were found to have a pericentric inversion of chromosome 19. A review of four previous cases, together with those reported here, suggests that inversion of chromosome 19 is not related to the phenotypic features of the probands. Furthermore, there has been no report of an affected subject resulting from a duplication deficiency product of inverted chromosome 19 among the offspring of inversion heterozygotes. The suggested association of aneuploidy in the inversion carriers is also discussed. [ABSTRACT FROM PUBLISHER]

An extreme variation of the short arm of no. 21 chromosome in the mother of a 21/21 translocation mongol is described. The possible relation between the very long short arm of chromosome no. 21 in the mother and a centric fusion type of translocation mongolism in the offspring is discussed. [ABSTRACT FROM PUBLISHER]

We present four children with a ring chromosome 6. Clinically, these cases are quite variable. A review of ten previously reported cases also suggests difficulty of phenotype-karyotype correlation in patients with a ring 6.

This communication describes the fourth known patient with a terminal long arm deletion of chromosome 10. The karyotype is : 46,XX,del(10)(q26). The clinical findings in the patient included intrauterine growth retardation, microcephaly, truncus arteriosus type 1, respiratory distress and craniofacial dysmorphism. Although review of the limited number of patients with a similar deletion reveals several common features, there is yet insufficient evidence to define a distinct 10q--syndrome.

This communication describes three unrelated patients with growth and psychomotor retardation, multiple congenital anomalies, and dysmorphic features who were found to have trisomies for the different long arm segments of chromosome 10. After reviewing the clinical and cytogenetic data from the literature and our three patients we concluded that: a) There are at least two different clinical syndromes associated with long arm trisomy of chromosome 10 only one of which, the well known 10q trisomy syndrome, is characterized with specific clinical features. The only trisomic segment common in this latter group of patients with similar phenotype, yet with different trisomic segments, is the distal two bands, q25 and q26. Therefore the determinants for the well-delineated 10q trisomy syndrome seems to be located on the distal bands q25 and q26 and this syndrome would preferably be named "distal 10q trisomy syndrome". b) The patients with proximal and/or middle long arm segment trisomies of chromosome 10 are rare and they have yet undefined clinical features.

In early infancy, two unrelated children with Smith-Lemli-Opitz syndrome were found to have elevated levels of androgen sulfates. When the steroid conjugates in the serum of normal infants were hydrolyzed and chromatographed on Sephadex LH-20, 4 androgen containing peaks (I, II, III, IV) were found. In the serum from these two infants with Smith-Lemli-Opitz syndrome, Peaks I and III were increased, but Peaks II and IV were absent. The parents of the two children, and of three additional unrelated children with Smith-Lemli-Opitz syndrome, had exaggerated 17-hydroxyprogesterone responses to an intravenous bolus of ACTH. These findings suggest that a defect in steroid metabolism may be linked to the Smith-Lemli-Opitz syndrome.

Partial trisomy for the long arm of chromosome 6, involving 6q22 leads to 6qter, was observed in a 2-month-old male infant. The mother was 6q;21p translocation carrier. A review of the previously published cases with trisomies of different 6q segments suggests that the critical segment responsible for the clinically recognizable phenotype of 6q trisomy seems to be limited to bands 6q26 and/or 6q27.

Several members of a family with a translocation between the short arm of chromosome 9 and the long arm of chromosome 13(9p--;13q+) are presented. Although the translocation found in various members of the family looked alike and appeared to be balanced, the clinical features were different. The like-sex twins displayed some features of 9p monosomy syndrome, whereas their mother and maternal grandmother, who apparently had the same translocation, showed only a few features of 9p-- syndrome in addition to mild mental retardation. We suggest that a minute deletion of the short arm of chromosome 9 may cause features of 9p-- syndrome and that the clinical features of this syndrome in older individuals may be too mild for the clinical diagnosis to be possible.

A partial trisomy for the short arm of chromosome 2 (p21 leads to pter) was observed in a severely retarded infant with facial, skeletal, genital, renal, and CNS anomalies. The phenotypically normal mother and older brother had a balanced translocation between the short arm of chromosome 2 and the long arm of chromosome 14: 46, XX-XY,t(2;14)(p21;q32).

A partial duplication of the distal segment of the long arm of chromosome 5 (q31 leads to qter) was observed in an infant with congenital malformations and dysmorphic features. The phenotypically normal father had a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 9: 46,XY,t(5;9)(q31;p24). The clinical and cytogenetic data obtained from six patients with partial duplications of two different long arm segments of chromosome 5 suggest that partial duplication of the distal long arm of chromosome 5 is associated with microcephaly, hypertelorism, epicanthus, strabismus, large upper lip, low-set, dysplastic ears, in addition to growth and psychomotor retardation. Partial duplication of the proximal part of the long arm of chromosome 5, on the other hand, is associated mainly with musculoskeletal abnormalities including muscle hypotrophy and hypotonia, scoliosis, lordosis, pectus carinatum, cubitus valgus, and genu valgum, in addition to psychomotor retardation. The dysmorphic features in this latter group include a bulging forehead, short nose, thick upper lip, low-set protruding ears and tapering, thin fingers.

Women who have a greater chance of having a high-risk pregnancy can benefit most from counseling before pregnancy occurs. These women include older individuals, those with recurrent pregnancy loss, members of specific ethnic groups, those exposed to potential teratogenic agents, patients with metabolic or genetic diseases, and those with an obstetric history of isoimmunization, previous cesarean section, or preterm delivery. Preconceptional counseling is an extension of prenatal care intended to minimize the maternal and fetal risk, to prevent birth defects, and to provide high-risk women with information about the risk and available options. Most of these options are viable only if the patient is aware of their availability before attempting conception. It is the physician's responsibility to provide preconceptional counseling to such women or to refer them to centers where such counseling services are available.

We present a phenotypically normal woman with del(X)(q26) with no evidence of mosaicism, who had two pregnancies resulting in two live-born infants. Her first child had trisomy 21 Down syndrome and the del(X)(q26). To our knowledge, this woman is the first known case of presumably nonmosaic del(Xq) producing live-born infants. This finding can be explained on the basis of persistence into adulthood of germ cells in ovaries of the rare del(Xq) individuals. The normal phenotype in this woman supports the hypothesis that the absence of genes of middle Xq segment (q13 leads to q26) is responsible for the somatic manifestations of the Ullrich-Turner syndrome. Our finding suggests that prenatal diagnosis should be offered not only to pregnant women with numerical X chromosome abnormalities, as suggested previously, but also to those with structural X chromosome abnormalities, because of the possibility of chromosome aberrations in the offspring of such women.

Extra chromosome material on the short arm of chromosome no. 6 (46,XY,6p+) was found in two mentally retarded adult half-brothers with mildly dysmorphic features. The phenotypically normal mother had a balanced translocation between the long arm of chromosome no. 1 and the short arm of chromosome no. 6:46,XX,t(1;6)(q32;p25). Thus the two affected brothers were trisomic for the long arm segment of chromosome no. 1, distal to q 32. These patients, with mildly dysmorphic features and mental retardation, represent the first cases of partial trisomy 1q surviving to adult-hood. The clinical and cytogenetic data obtained from eight individuals with partial trisomies for different long arm segments of chromosome no. 1 suggest that partial trisomy of the distal two-thirds of the long arm in characterized by severe malformations, growth retardation, and early death. Conversely, partial trisomy for the distal one-third of the long arm is associated with milder malformations and longer survival time as well as growth and mental retardation.

A newborn female infant presented with hypotonia, joint hyperextensibility, cardiac murmur, macroglossia, and hepatosplenomegaly. Karyotype of the child revealed partial trisomy of chromosome 11p derived from a paternal balanced translocation. Echocardiogram obtained in the newborn period suggested interatrial aneurysm, which was confirmed on post-mortem examination. Interatrial septal aneurysm is a rare abnormality not previously described in partial trisomy 11p.

Characteristic radiographic findings of absence of the left pericardium were observed in two relatives who were related to two other individuals with different types of congenital heart defects. Familial occurrence of congenital absence of pericardium has not been reported previously. The strong male sex predilection in the previously reported patients, the segregation pattern of affected individuals in the pedigree presented here, and the presence of two other individuals with multifactorially determined congenital heart defects in the same pedigree suggest multifactorial determination of congenital absence of the left pericardium.

Association patterns of acrocentric chromosomes in 3032 cells from chromosomally normal parents of regular mongols (nondisjunctional trisomy 21) and normal controls were studied by the Giemsa banding technique. In each group, chromosome No. 21 was found to be involved in satellite association more frequently than other acrocentric chromosomes. The most frequently seen association was between No. 21 and 22. However, no difference was shown between the parental test group and the normal controls in regard to these frequencies. These results render less tenable the proposed linkage between satellite association and the etiology of mongolism.

Hemifacial microsomia, a relatively distinct clinical form in the Facio-Auriculo-Vertebral Spectrum is generally thought to be a sporadic event, although infrequent familial occurrences have been reported. In this communication, we describe a family with three males and two females in two successive generations affected with hemifacial microsomia. The pedigree is most compatible with autosomal dominant inheritance, although X-linked dominant or multifactorial inheritance cannot be excluded.

This communication describes a 7-year-old male with growth and psychomotor retardation and dysmorphic features who has a small terminal deletion of the long arm of chromosome 7. The proband, in addition, had bilateral coloboma of the retina and choroidea which was not reported previously in patients with this rare chromosomal deletion syndrome. Our finding and available data in the literature on the association of the coloboma of the eyes with various chromosomal abnormalities points out the importance of karyotype studies in such patients, especially in the presence of concomitant extraocular findings.

The del (18q) syndrome is characterised by poor growth, variable mental retardation, facial dysmorphism, and abnormalities of the genitalia. In genetic males, genital abnormalities vary from testicular ectopia, and microphallus to severe hypospadias. Genetic females frequently have hypoplasia of the labia minora. We describe a child with del (18q) syndrome and severe ambiguous genitalia. Serum testosterone after 4 doses of hCG (5000 IU/m2/dose) was only 50 ng/dL (expected greater than 300 ng/dL). When testicular tissue was incubated with [1,2-3H]progesterone and 17-hydroxy-[4-14C]progesterone, there was synthesis of 17-hydroxy-[1,2-3H]progesterone but no further metabolism of 17-hydroxyprogesterone to androgens. These data suggested the presence of steroid-17,20-lyase deficiency. In order to determine if steroid-17,20-lyase deficiency was a common feature in del (18q) syndrome we examined 6 other patients (3 girls; 3 boys) with a deletion of the long arm of chromosome 18 distal to band q21. All 6 had dehydroepiandrosterone sulfate (DHEA-S) levels which were lower than those of age-matched controls. Four had delayed puberty. Serum testosterone levels were also low in 2 of the 3 affected boys. These results together with the findings in the index case suggest that a structural or regulatory gene for steroid-17,20-lyase may be located on the long arm of chromosome 18, distal to band q21.