Arthur Robinson

The 11q;22q translocation: A collaborative study of 20 new cases and analysis of 110 families

SummaryFollowing a previous collaborative study (Fraccaro et al. 1980), 20 new cases of 11q;22q translocation are described. Twelve families were ascertained through an unbalanced carrier of the translocation and eight cases were ascertained as balanced carriers. A segregation analysis was performed on the 110 families so far published. It was concluded that the 11q;22q translocation is a relatively frequent event, and that all the cases thus far reported might have the same breakpoints at 11q23.3 and 22q11.2. The translocation seems to be independent of environmental factors and it seems to have a low rate of mutation as indicated by the scarcity of de novo cases. The new data confirmed that only one type of unbalanced karyotype (47,XX or XY+der(22)t(11;22)(q23.3;q11.2)) is found among the offspring of the translocation carriers. The minimal overall recurrence risk for an unbalanced translocation was estimated to 2%. There was no difference between the recurrence risks for male and female balanced carriers, while the trend was confirmed of an excess of female balanced carriers among the phenotypically normal offspring of the t(11;22) female carriers.

4;11 translocation in acute lymphoblastic leukemia: a specific syndrome.

Abstract Three patients with acute lymphoblastic leukemia (ALL) having t(4;11) (q21;q23) are described. Their clinical characteristics are compared with ten other published cases all involving similar histories and poor prognoses.

Cognitive Development of Children with Sex Chromosome Abnormalities

Sex chromosome abnormalities (SCA) are genetic disorders associated with a variety of developmental problems, including learning disorders (LD). The study of SCA provides a unique opportunity to increase understanding of genetic and developmental features of LD. Most research on the genetics of LD involves cross-sectional or retrospective study of children in order to trace familial patterns of transmission of problems of unknown cause. In contrast to such heterogeneous samples, children with LD and the same SCA share a single genetic factor. The possibility of identifying an LD subtype of specific genetic causation is thus greatly increased, especially when the study is prospective (Pennington et al., 1982). Longitudinal evaluations of children with SCA may elucidate the relationship between physical and cognitive development and help to establish the processes by which SCA is associated with LD. This knowledge in turn may increase understanding of the role of the sex chromosomes in normal cognitive development.

Transition from adolescence to early adulthood: adaptation and psychiatric status of women with 47,XXX.

OBJECTIVEnTo investigate the adolescent and early adult adaptation of a group of 47,XXX women as compared with their siblings, addressing developmental differences in adaptation and psychiatric status.nnnMETHODnSubjects included eleven 47,XXX women and nine female sibling controls. Interviews during adolescence and during early adulthood were semistructured and included a psychiatric evaluation. Four areas of inquiry were (1) relationships with other family members, (2) sense of self-esteem, (3) sexual identity and preference, and (4) responses to life stressors. A DSM-IV psychiatric diagnosis was assigned where appropriate. The Schedule for Affective Disorders and Schizophrenia-Lifetime version was also administered, and assessments of overall functioning and adaptation were completed.nnnRESULTSnThe 47,XXX women during adolescence and young adulthood were less well adapted; had more stress; had more work, leisure, and relationship problems; had a lower IQ; and showed more psychopathology when contrasted with the comparison group. However, most of the 47,XXX women were self-sufficient and functioning reasonably well, albeit less well than their siblings.nnnCONCLUSIONSnThis longitudinal study has clarified that previously reported outcomes of severe psychopathology and antisocial behavior in individuals with sex chromosome anomalies are rare and variability in the behavioral phenotype is much larger than originally appreciated.

Thymic alymphoplasia with XX/XY lymphoid chimerism secondary to probable maternal-fetal transfusion†††

Karyotypes in a 5-month-old patient with thymic alymphoplasia revealed evidence for XX/XY chimerism in peripheral blood lymphocytes. These cells showed no immunologic competence, and there was no indication of a graft-versus-host reaction (GVHR). These findings suggest that placentally transfused maternal lymphocytes may persist in an immunologically incompetent fetus without having a demonstrable effect. Additional findings included adrenal hyperplasia, possible absence of parathyroids, and lack of evidence of immunologic function after attempts at grafting fetal thymic and hematopoietic tissue.

Environment and Developmental Risk in Children With Sex Chromosome Abnormalities

Abstract Forty-six children with sex chromosome abnormalities (SCA), identified in the chromosome screening of 40,000 consecutive newborns between 1964 and 1974, have been studied longitudinally. Language, motor, psychosocial, and school impairment occurred more frequently in the 38 nonmosaic propositi but not in the 8 mosaic propositi, relative to the group of 32 control siblings. Incidences of motor, school, and psychosocial impairment increased dramatically when the SCA children came from dysfunctional families, as rated by the Family Dysfunction Index, but not in control subjects. Biological factors that influence environmental risk are discussed, and the importance of understanding “protective factors” in unaffected SCA children noted.

Tuberculin Hypersensitivity in Tuberculous Infants Treated with Isoniazid

THE purpose of this paper is to record marked decrease of skin tuberculin hypersensitivity in 4 tuberculous infants during isoniazid therapy, and to discuss the possible implications of this phenomenon. Nine other cases are presented in which the hypersensitivity did not occur. Observations The group of cases in which tuberculin hypersensitivity was greatly diminished is described in Table 1. All 4 of these patients were under two years of age, were found to have positive skin reactions to old tuberculin (definitely positive Mantoux reactions to 1:1000 dilution) on contact examination and had normal roentgenograms of the chest. They were all treated .xa0.xa0.

The development of four unselected 47,XYY boys

Four infants identified through neonatal screening programs are an unselected sample of 47,XYY boys. No consistent physical stigmata or medical disorders were identified. Three have increased height. All four demonstrated problems in motor and language development. Although their intelligence is within the average range, all four have language‐related learning disorders requiring special education. Mild depression was apparent in all four, perhaps as a secondary result of their learning disorders. Some of the problems seen in the propositi are found in milder forms in other family members, leading to the hypothesis that their karyotype may heighten vulnerability to pre‐existing familial conditions. Similarities between these findings and results from seven other study centers with a total of 42 47,XYY boys are noted. Parents of a prenatally diagnosed 47,XYY fetus seen in our center are informed that the extra Y chromosome represents a risk factor for these problems, but that environment remains a primary force in shaping their childs development.

Multiple keukemic clones in acute leukemia of childhood

SummaryTwo abnormal karyotypes representing clonal populations have been demonstrated in three patients in the early stage of acute leukemia. The karyotypes were apparently unrelated in one patient, while in the other two, a relationship was conjectured. Both clones were present before therapy in two patients. Although a clone resistant to therapy was associated with relapse in one case, in two cases a clone has persisted in the lymphocyte culture during drug treatment with the patients in remission.

9;22;15 complex translocation in Ph1 chromosome positive CML revealed by Giemsa-11 procedure in apparent lymphoid cells of blastic crisis

A Ph1 chromosome positive chronic myeloid leukemia patient whose chronic phase lasted 7.5 years experienced a blastic transformation originating in the spleen. The spleen was infiltrated with undifferentiated blast cells that on cytogenetic analysis had a hyperdiploid karyotype and were Ph1 chromosome positive. The blast cells were negative for PAS, peroxidase. Sudan black and esterase stains. They were non-T, non-B with TdT activity. Remission was achieved in response to prednisone, vincristine, and adriamycin. Ph1 positive cells were present with cells responding to PHA stimulation throughout the course of the disease. A Giemsa-11 staining procedure male possible the ascertainment of a No. 9 translocation chromosome in blastic crisis cells that had also been present in Ph1 chromosome positive cells early in the disease. The presence of this translocation initially in myeloid cells and subsequently in apparent lymphoid cell types suggests the origin of this patients leukemia as a pluripotential stem cell.