Deformidad en coxa vara en la disóstosis cleidocraneal / Coxa vara deformity in cleidocranial dysostosis

La disostosis cleidocraneal es una rara displasia ósea generalizada. La coxa vara o disminución anormal del ángulo de inclinación del cuello femoral está frecuentemente presente en la disostosis cleidocraneal. Se presenta un nuevo caso y se discute la revisión de la bibliografía (AU)

47,XXY/48,XXY,+21 chromosomal mosaicism presenting as hypospadias with scrotal transposition.

The syndrome of 47,XXY/48,XXY,+21 chromosomal mosaicism, double aneuploidy, is extremely rare and characterized by combined manifestations of Klinefelter's and Down's syndromes. We report a case of XXY/XXY,+21 mosaicism presenting with hypospadias associated with scrotal transposition.

Chromosome 22 abnormalities in Ewing's sarcoma.

A child with disseminated Ewing's sarcoma underwent cytogenetic investigations which showed different structural rearrangements of chromosome 22 at diagnosis (?ring22), and at relapse [t(10;22)], but the classic translocation t(11;22) was not detectable. This case provides further evidence of the importance of chromosome 22 in this disease, while raising some questions about the central importance of the translocation between chromosomes 11 and 22.

Refractoriness to chemotherapy and poor survival related to abnormalities of chromosomes 17 and 7 in lymphoma.

PURPOSE: Lymphoma cells usually show cytogenetic abnormalities, but their relationship to prognosis has not been as extensively studied as in leukemia. A group of previously untreated cases of lymphoma with evaluable metaphases was examined for the association between cytogenetic abnormalities and clinical outcome. PATIENTS AND METHODS: The study consisted of 104 patients, from whom fresh tumor samples were obtained for cytogenetic tests. Because of the complexity of lymphoma karyotypes, the cases were divided into four patterns according to the type of abnormality of chromosome 17 or 7 present. Treatment of patients was given based on histologic grade and stage of disease. Response to treatment was evaluated according to previously described methods. RESULTS: Patients with true abnormalities of chromosome 17 or 7 (defined as those with either structural abnormalities of the short arm of these chromosomes or monosomy of these chromosomes with no associated unidentified markers) were observed to have an adverse prognosis. The overall response rate and tumor-related mortality were less favorable for patients with these cytogenetic abnormalities. By applying multivariate analysis, we found that this observation was independent of the effect of serum lactic dehydrogenase level, histologic grade, or tumor burden. CONCLUSION: True abnormalities of chromosome 17 or 7 in patients with lymphoma are associated with a poor response to chemotherapy, short time to treatment failure, and high tumor-related mortality rate. These findings raise the question of the potential involvement of some gene or oncogene, perhaps the p53 oncogene, which might impart a survival advantage to the malignant cells.

Proto-oncogene abnormalities and their relationship to tumorigenicity in some human glioblastomas.

Human glioblastomas are highly malignant intracranial tumors, some of which demonstrate amplification of the epidermal growth factor-receptor (EGF-R) gene. Overexpression of this gene is seen in the majority of primary tumors; however, the role of the EGF-R gene in glial tumorigenesis is unknown. The authors explored the relationship between EGF-R gene expression and glioblastoma cell growth in vitro and in vivo and found that this level of EGF-R gene expression did not correlate with tumor cell growth either in soft agar or in the nude mouse. This suggests that the EGF-R gene is not involved in effecting direct growth stimulation in glial oncogenesis. Tumorigenesis involves differentiation arrest; therefore, the expression of several proto-oncogenes in neuroectodermal tumors was investigated to evaluate the potential involvement of the EGF-R gene in glial differentiation. A nonoverlapping expression of the N-myc and EGF-R genes was found in neuronal-derived and glial-derived tumors, respectively. This suggests that the EGF-R gene may be involved in differentiation or its arrest in glia.

Antenatal detection of cystic hygroma.

Ultrasonographic evaluation, as a routine component of prenatal care, has significantly contributed to in utero assessment of pregnancy status. The detection of fetal abnormalities by ultrasound, however, has raised clinical questions and created parental dilemmas concerning the outcomes of such pregnancies. A relatively frequent anomaly observed on routine ultrasonographic examination is the posterior nuchal cystic hygroma. We report the prenatal detection of 16 cases of cystic hygromata and an analysis of a survey of the world's literature including an additional 155 cases. The information available from these 171 cases allows a clearer picture of the prognosis for fetuses in whom posterior cystic hygroma is detected in utero. Regarding outcome, 73.2 per cent of cases were terminated at the parents' request; 37 cases (22.6 per cent) resulted in fetal death in utero prior to any intervention. Only 7 per cent of continuing pregnancies resulted in live-born infants. Of the 142 cases with available cytogenetic findings, 22 per cent had normal karyotypes; 58 per cent had a karyotype associated with Turner syndrome phenotype; while autosomal trisomies and various structural abnormalities made up the remaining 20 per cent. Even among those fetuses with normal chromosomes, various physical anomalies were detected. Fetal hydrops was present in 66 per cent of the 102 cases with pertinent information. For those fetuses demonstrating cystic hygroma and normal karyotypes, Mendelian syndromes must be considered in the differential diagnosis. Alpha-fetoprotein evaluation of both maternal serum and amniotic fluid was not helpful in determining prognosis of these fetuses. The ultrasonographic finding of a posterior nuchal cystic hygroma, with or without accompanying fetal hydrops, is a valid indicator for a poor outcome of such pregnancies.

Chromosomal abnormalities in fetuses with omphalocele. Significance of omphalocele contents.

Twenty-six consecutive fetuses with a sonographically detectable omphalocele and known karyotype were reviewed to identify risk factors that might be associated with chromosomal abnormalities. Risk factors that were analyzed included contents of the omphalocele sac, maternal age, fetal sex, sonographically detectable concurrent anomalies, and any major concurrent anomaly. Chromosomal abnormalities were found in 10 cases (38%) from trisomy 18 (n = 4), trisomy 13 (n = 4), trisomy 21 (n = 1), or 45, X (n = 1). The absence of liver from the omphalocele sac (intracorporeal liver) was strongly associated with an abnormal karyotype; chromosomal abnormalities were present in all 8 fetuses with an intracorporeal liver compared to 2 of 18 fetuses with an extracorporeal liver (p less than .0001, two-tailed Fisher exact test). Other risk factors that were statistically associated with chromosomal abnormalities included advanced maternal age (greater than or equal to 33 years, p = .03) and sonographically detectable concurrent malformations (p = .05). We conclude that sonographic findings can help determine the relative risk of chromosomal abnormalities in fetuses with omphalocele; abnormal karyotypes were significantly associated with the absence of liver from the omphalocele sac and sonographically detectable concurrent malformations in this series. Sonographers should also be aware that omphaloceles that contain bowel alone tend to be small and can be missed or mistaken for other abdominal wall defects (gastroschisis or umbilical hernia).

Extramedullary blast crisis and hemolytic anemia in a patient with t(3p+;4q-) and rapidly evolving myelogenous leukemia.

We have reported the case of a patient with a rapidly evolving myelogenous leukemia associated with hemolytic anemia, extramedullary evolution, and an isolated translocation of the long arm of chromosome 4 to the short arm of chromosome 3. The hemolytic process was primarily extravascular and was not associated with pyruvate kinase or glucose-6-phosphate dehydrogenase deficiency. Although blasts were absent from the peripheral smear and represented less than 10% of the bone marrow myeloid precursors, multiple organs including the heart, liver, lungs, and spleen were infiltrated with blasts at autopsy.

[Childhood obesity as a symptom of genetic syndromes]. / Detská obezita jako príznak genetických syndromu.

The authors describe on examples from the practice of a genetic clinic seven different genetic syndromes associated with obesity: Laurence-Moon-Biedl, Alström, Weiss, Cohen, Carpenter, Prader-Willi and syndrome of insulin resistance. The autosomal recessive determination of the majority of these syndromes emphasizes their genetic impact with a high risk of repeated occurrence in the family. Visual and hearing defects increase clinical and social importance of these syndromes. When evaluating the genetic prognosis of risk families, the authors consider the possibility of prenatal diagnosis and its forms and the risk of implementation of a preventive method. In some instances obesity is a manifestation of a disorder of insulin receptors.

DNA index and karyotype analysis in myelodysplasia.

DNA index (DI) determined by flow cytometry and karyotype determined by conventional methods were obtained on bone marrow samples from 43 haematologically normal subjects and 54 patients with myelodysplastic syndrome (MDS). Twenty one patients had a clonal karyotype abnormality but an additional five had a DI outside the normal range, showing evidence of aneuploidy that was not available from chromsome preparations. When patients were grouped into those with excess chromosomal material, those with diploid karyotypes, and those with a loss of chromosomal material, there was a significant difference among the mean DIs of each group, normal subjects being different from all patient groups. In these patients DI measurements were of value when carried out together with conventional chromsomal analysis in gaining the maximum amount of genetic information when a satisfactory karyotype might not be available or where failure of an abnormal cell population to proliferate might give an incomplete cytogenetic picture. The contribution of non-clonal chromsome loss to the DI is probably significant but has not been quantitated.

Hybrid acute leukemia in an HIV-antibody-positive patient.

Although the great majority of acute leukemias have been designated as being of lymphocytic or myelocytic origin, recent reports have described elements of both in some patients. We describe here the first case of hybrid acute leukemia in an HIV-antibody-positive patient as well as the first hybrid involving B-cell (Burkitt) acute lymphocytic leukemia and acute myelomonocytic leukemia proven by cytochemical, immunologic, and cytogenetic methods. This case illustrates the increasingly complex difficulties in the diagnosis and treatment of AIDS-related malignancies.

Clinicopathologic and cytogenic features of CD34 (My 10)-positive acute nonlymphocytic leukemia.

The authors performed membrane antigen phenotyping on 75 patients with acute nonlymphocytic leukemia with a panel of myeloid-associated monoclonal antibodies. The 34 patients (45%) with CD34-positive leukemia were not significantly different from the 41 with CD34-negative leukemia with respect to age, hemoglobin, white blood cell count, or platelet count at presentation, but their blasts were more likely to lack the CD15 or CD33 antigens and to have FAB M1 or M2 morphologic characteristics. CD34-positive leukemia was more likely to arise after chemotherapy. Patients with CD34-positive leukemia were less likely to enter a complete remission even when analysis was limited to those patients receiving a high-dose induction-type chemotherapy regimen. Giemsa-banding karyotyping studies were obtained in 55 of the cases. In 30 of these cases (56%) clonal karyotypic abnormalities were demonstrated. Although the karyotypic abnormalities and phenotypes were varied, there was a high degree of association between the karyotypic abnormalities monosomy 7/del (7q) and the CD34-positive phenotype; this antigen was expressed on blasts from eight of the nine patients displaying this abnormality. Monoclonal antibody phenotyping of myeloid leukemia with reagents such as anti-CD34 may help to define biologically interesting subsets of ANLL with distinct clinicopathologic expression.

High-dose cytosine arabinoside and daunorubicin as primary therapy in elderly patients with acute myelogenous leukemia. A phase I-II study of the Southeastern Cancer Study Group.

We undertook a phase I-II trial in elderly (age greater than or equal to 60 years) untreated acute myelogenous leukemia (AML) patients using brief, intensive therapy to improve induction rates and overall survival in older AML patients. Twenty-one patients ranging in age from 60 to 81 years (median, 66 years) were treated using either a 4- or 5-day course of high-dose cytosine arabinoside, 3 g/m2 intravenously (IV) every 12 hours; followed by daunorubicin, 45 mg/m2/d IV bolus for 3 consecutive days. Thirteen patients were entered at the first dose level (a 4-day course or eight doses of cytosine arabinoside), whereas eight patients underwent therapy at the second dose level (a 5-day course or ten doses). Patients who achieved a complete remission received a repeat course of high-dose cytosine arabinoside and daunorubicin within 4 weeks of attaining remission. Seven patients had an antecedant history of a myelodysplastic syndrome. Infection was the major complication experienced by this elderly patient group, and included ten episodes of bacteremia or fungemia (four of which were fatal) and five cases of pneumonia (one fatality). Nine of the 21 patients (three of 13 at the first dose level and six of eight at the second dose level) achieved a complete remission. Median remission duration was 9 months (range, 4-19+ months). Although high-dose cytosine arabinoside plus daunorubicin was an effective antileukemic therapy, it is too toxic to recommend for most elderly leukemic patients.

Prenatal diagnosis and management of congenital heart disease.

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.

[Chromosome aberrations in a group of mentally retarded persons]. / Chromozómové aberácie v súbore mentálne retardovaných jedincov.

Mental retardation (MR) is a frequent manifestation in patients referred to departments of medical genetics (OLG). At the OLG in Martin their number in the years 1981-1985 was 324, i.e. 21.22% of the total number of examined subjects. MR was found as one of the pathological symptoms (symptomatic MR) in 86.73% and as the only pathological manifestation (isolated MR) in 13.27%. Genetic factors were revealed in 59%, exogenous ones in 19%, and in 22% the aetiology was not unequivocally resolved. As to genetic factors, the most frequent cause were chromosomal aberrations (in 104 patients-53%), a monogenic character was found in 68 subjects (35%) and a multifactorial one in 24 (12%). As to chromosomal aberrations, in 102 cases autosomes were affected (91 times numerical and 11 times structural affection), in four subjects a numerical anomaly of genosomes was involved and once a combined aberration of an autosomal and gonosomal character. The authors give the character and number of different types of aberrations and the incidence of so-called chromosomal markers (12 cases) and they evaluate their causal relationship with MR. Further advances in the aetiological evaluation of genetic factors will be made possible by the introduction of strip methods with a high resolution technique (use of prophasic chromosomes), combined with hybridization in situ, cytogenetic methods for the detection of individuals with the fragile X-chromosome syndrome, and in particular the application of the technology of recombinant DNA for the diagnosis of clinical and genetic units at the gene level.

Evaluation of severe growth retardation using cordocentesis--hematologic and metabolic alterations by etiology.

Hematologic and respiratory blood gas parameters were studied in 21 fetuses with severe or early-onset (at or before 34 weeks) growth retardation and in 44 age-matched control fetuses. Diagnostic categories included uteroplacental insufficiency (N = 7) and uteroplacental insufficiency with associated fetal structural abnormality (N = 7), aneuploidy (N = 5), and congenital infection (N = 2). The mean (+/- 1 SEM) gestational age was 29.3 +/- 1 week. Compared with the control group matched for gestational age, the growth-retarded fetuses had higher hematocrits regardless of etiology. The platelet count was reduced in growth-retarded fetuses with aneuploidy (P less than .05). Leukopenia was observed in a fetus with congenital infection and in the group of fetuses with uteroplacental insufficiency unassociated with a structural abnormality (P less than .05). Leukocytosis was seen in growth-retarded aneuploid fetuses (P less than .01). The pH, pO2, and percent oxygen saturation were each lower in growth-retarded fetuses with either uteroplacental insufficiency or aneuploidy, and the pCO2 and bicarbonate were higher compared with controls (each P less than or equal to .05). Appropriately grown aneuploid fetuses had normal hematologic and respiratory blood gas measurements but were significantly more likely not to be trisomic (P = .04). Fetuses with uteroplacental insufficiency unassociated with a structural anomaly had significantly higher umbilical artery systolic/diastolic ratios than both the control group (P = .0002) and the group with uteroplacental insufficiency and a structural anomaly (P less than .008). This investigation confirms previous studies of fetuses suffering uteroplacental insufficiency and extends the observations to other etiologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome pattern in juvenile chronic myelogenous leukemia, myelodysplastic syndrome, and acute leukemia associated with neurofibromatosis.

We studied chromosomes of BM cells from four neurofibromatosis (NF) patients with leukemia. One patient had a normal diploid karyotype in the chronic phase of juvenile chronic myelogenous leukemia (JCML). When the the leukemia evolved into the accelerated phase, she had cells with 46,XX,-7,+der(7)t(3;7)(q21;p22); the abnormalities resulted in a partial 7p deletion. In another patient with JCML, BM cells in the accelerated phase had 45,XY,-7. The abnormal cells with monosomy 7 disappeared from the BM after chemotherapy but reappeared later in the course. Another patient developed refractory anemia with excess of blasts in transformation (RAEB-T) and had cells with 46,XX,-6,+r(6)(p23?q21?); the abnormalities resulted in partial 6p and 6q deletions. The other patient with ANLL had cells with 45,XX,-7. Our findings and review of data on nine other patients suggest that BM cells of NF patients with JCML in chronic phase have no microscopically detectable chromosome changes and that cells with chromosomal deletion emerge when JCML evolve into the accelerated or blast phase. Thus, deletion of the whole or part of certain chromosomes, such as chromosomes 6, 7, etc., may be an important step towards the evolution of JCML cells or the development of de novo acute leukemias in NF patients.

Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study.

The Baltimore-Washington Infant Study is a population-based case-control study that seeks to identify risk factors for cardiovascular malformations. Between 1981 and 1986, a total of 2102 infants with cardiovascular malformations were ascertained, among whom 271 (12.9%) also had a chromosome abnormality. Among 2328 random control subjects, only two had a chromosome abnormality. Down syndrome with cardiovascular malformations had a maternal age-adjusted regional prevalence of 4.33/10,000 for the white population and 3.70/10,000 for the nonwhite population. Endocardial cushion defect, the predominant cardiac abnormality in Down syndrome (60.1%), rarely occurred as an isolated cardiac lesion (2.8%). The absence of transpositions and the rarity of heterotaxias and of right- and left-sided obstructive lesions in trisomies indicate that there may be a genetic influence on specific embryologic mechanisms. Alimentary tract lesions were more common in Down syndrome than among euploid patients with heart disease and more severe than in control subjects. Urinary tract lesions also occurred in excess of the rate in control subjects. The coexistence of these major malformations with heart disease raises the possibility of incomplete expression of the VA(C)TER (vertebral, anal, cardiac, tracheal, esophageal renal) association. The selective association of chromosome abnormalities with certain cardiovascular defects is now beginning to be explained by reported embryologic studies on cellular characteristics. An explanation of the negative association with transposition and obstructive lesions requires further multidisciplinary studies on genetic and epigenetic factors.

Cytogenetic studies in couples with recurrent pregnancy loss.

We reviewed the results of lymphocyte karyotypes from 232 couples who had had two or more pregnancy losses (spontaneous abortions or stillbirths). Despite the use of strict criteria to correct for possible bias of ascertainment, 8% of these couples (19 of 232) had a chromosome abnormality. Six of these abnormalities were low-percentage mosaicism for aneuploidy or a translocation. If these couples were excluded, 13 (6%) of the study couples had a chromosome abnormality. There was no significant difference in the incidence of chromosome abnormalities in those couples having two losses as compared with those having three or more losses. The study couples were referred from a wide range of sources, and most women had not had extensive gynecologic evaluation. These results confirm the importance of cytogenetic analysis of couples with recurrent pregnancy loss, and suggest that such studies be considered after two losses.