Two cases of C-group balanced translocations.

The present study describes 2 cases of a balanced reciprocal translocation in the C-group of autosomes. Familial translocation 46,XX,t(6;7) was found both in a woman cytogenetically examined because of a developmental anomaly of the internal genitals (uterus bicornis subseptus) and in her healthy mother. Chromosomal complement 46,XYt(8;10) was proved in the healthy father of a child showing clinical features of Down's syndrome with a karyotype 47,XY,21+. Q- and G-banding techniques were used for precise identification of the chromosomes involved in translocations.     

Translocation (14;21)(q11;q22) in a woman with history of abortions and a child with Down's syndrome

A translocation (14;21)(q11;q22) was observed in a woman with history of abortions and in her child with Down's syndrome. This appears to be the first report of such a translocation with no centric fusion between the acrocentric chromosomes leading to a count of 45 chromosomes in the carrier and giving birth to a Down's syndrome child.     

Maternally transmitted extra ring(21) chromosome in a boy with Down's syndrome

Summary An 11-month-old boy with typical Down's syndrome is presented. His karyotype was 47,XY,+r(21); the erythrocyte superoxide dismutase-1 (SOD-1) activity was elevated. His phenotypically normal mother showed 46,XX,r(21) karyotype and normal SOD-1 activity. Analysis of chromosomal heteromorphism revealed that in addition to the ring, a normal chromosome 21 was transmitted from the mother.     

The occurrence of a ring 18, an accessory bisatellited fragment,and trisomy 21 within one sibship

Summary A family is presented in which there were three different chromosome abnormalities in the children although the parents were cytogenetically normal. The proband had the karyotype 46,XX,r(18)(p11q23), a phenotypically normal brother was 47,XY,+mar, and another brother was a typical case of Down's syndrome, karyotype 47,XY,+21. There is nothing in the parents' history that provides grounds for a hypothesis to explain the coincidence of the abnormalities.     

Translocation (13q21q). Four generation family study with analysis of satellite associations, fluorescent markers, and prenatal diagnosis.

A (13q21q) translocation was found in an infant with Down's syndrome. The 17-year-old mother and the grandmother carried the translocation 45,XX,t(13;21)(p12;q11). The great grandparents had normal karyotypes. Fluorescence marker studies suggested that the translocation originated in the great grandmother. The hypothesis was supported by satellite association studies which showed a significant excess of 13-21 and 13-15 associations in the great grandmother.     

Unstable telocentric chromosome produced after centric misdivision of a 21q/21q translocated element

Summary An unstable telocentric chromosome was found in an individual with Down's syndrome and an unusual chromosomal mosaic, 46,XX, t(21q21q)+,21-/46,XX,21p-/45,XX,21-. As the 21q/21q chromosome was of paternal origin, based on the characteristics of its centromeric heterochromatin and on the characteristics of both 21 chromosomes of the father, it was concluded that its formation involved centric breakage and loss of centromeric material. The cell line with the 21p- chromosome may have originated from the translocation by an asymmetric misdivision of the reduced centromeric material. Of the two telocentrics produced by this fracture, one, possessing the smaller amount of centromeric apparatus, would be immediately lost; the other would be retained, but complete activity of its centromere would not be restored. It would therefore be unstable and might be lost.     

Molecular evidence for true isochromosome 21q

Summary In one family a duplicated 21q was shown to be a true isochromosome, which segregates from mosaic mother to non-mosaic child with full Down syndrome phenotype. Densitometric analysis of Southern blots, using probe pPW228C for the distal long arm of chromosome 21, indicated that the 21q duplication contains two copies of the allele detected by the probe. Maternal mosaic karyotype of 45,XX,-21/46,XX/46, XX,-21,+21i(21q) also suggested transverse mitotic centromere division as the origin of the 21q isochromosomes. Morphologic analysis of chromosome heteromorphisms strengthened this interpretation because the free 21 missing in the cell line with 45 chromosomes was also missing in cells with the isochromosome. In a second family the cytogenetic data also suggested transmission of an i(21q) from mosaic mother to nonmosaic Down syndrome child but molecular evidence did not prove identity of alleles in the duplicated chromosome 21.     

Translocation (13q21q)

Summary A (13q21q) translocation was found in an infant with Down's syndrome. The 17-year-old mother and the grandmother carried the translocation 45,XX,t(13;21)(p12;q11). The great grandparents had normal karyotypes. Fluorescence marker studies suggested that the translocation originated in the great grandmother. The hypothesis was supported by satellite association studies which showed a significant excess of 13–21 and 13–15 associations in the great grandmother.     

Familial Down's syndrome.

A family is reported in which the same mother conceived two children with trisomy 21. The pregnancy with the second affected child was interrupted after diagnostic amniocentesis. Maternal chromosome analysis was normal. This family and those previously reported suggest that there is an increased recurrence risk of trisomy 21 after the birth of an affected individual, possibly caused by a genetic tendency for non-disjunction. After the birth of a child with Down's syndrome, amniocentesis and chromosome analysis of cultured amniotic fluid cells is indicated in each further pregnancy, irrespective of maternal age.     

Prenatal cytogenetic analysis of women with high risk for genetic disorders

165 prenatal cytogenetic analyses are reported. The culture and Giemsa or quinacrine mustard (QM) staining processes are described. Karyotypes from both Giemsa and QM metaphases were analyzed. The main indications for amniocentesis were: 1)previous child with Down's syndrome (65), 2)advanced maternal age (74), 3)D/G carrier (5), 4)Duchenne muscular dystrophy (5) or 6)previous indication of other chromosomal anomaly. In the advanced maternal age group, 4 G21 and 1 E18 trisomy fetuses were detected. No chromosomal abnormalities were seen in the group referred for a previous child with Down's syndrome, although one woman was found to have a 9/13 translocation herself. Another woman with 13/14 translocation gave birth to a healthy boy with a 13/14 translocation, as predicted. Of 5 women referred for D/G translocation carriers, 1 had a fetus with a 46, X,Y,-D + t(DqGq) karyotype. Sex determination for X-linked anomalies resulted in detection of 2 Duchenne's muscular dystrophy, 1 hemophilia, 1 Norrie's syndrome, and 1 Pelizaeus-Merzbacher's syndrome.     

Partial trisomy (11;22) syndrome with manifestations of Goldenhar sequence due to maternal balanced t(11;22)

Here we report a 15-year-old girl patient who had severe mental and growth retardation, cleft palate, hemifacial microsomia, skin tags, hypoplasia of the external auditory canal, scoliosis and renal agenesis. Our patient was the fourth child of nonconsanguineous marriage. Peripheral blood chromosomal analysis of the patient revealed 47,XX,+der(22)t(11;22)(q23;q11). The maternal karyotype was reported as 46,XX,t(11;22)(q23;q11). Maternal balanced translocation t(11;22)(q23;q11) causing Goldenhar syndrome with 47,XX,+der(22) has not been reported previously. The presented case clearly indicates that in every case with Goldenhar syndrome, chromosome analysis should be done for the possibility of unbalanced translocations.     

Cytogenetic studies of a family with trisomy 21 mosaicism in two successive generations as the cause of Down's syndrome

Summary A family with trisomy-21 mosaicism in two successive generations and a Down's syndrome child in the third generation is presented. Cytogenetic studies of eight individuals of this family showed a marker chromosome 15ph+ and a heteromorphic chromosome 18 in some members. The standard trisomy 21 in the proband was derived from a trisomy-21 oogonium by secondary nondisjunction in his mother.     

Tandem duplication chromosome 21 in the offspring of a ring chromosome 21 carrier

A direct tandem duplication chromosome 21 was found in a boy with Down's syndrome. The proband's mother and grandmother both carried a ring chromosome 21. The observed duplication chromosome in the child may be explained either by recombination between the maternal ring and the mother's normal chromosome 21 or by break of a double-sized ring chromosome 21.     

Birth weight corrected for gestational age is related to the incidence of Down's syndrome pregnancies.

Three recent studies reported that early depletion of the primordial follicle pool is likely to be an independent risk factor for Down's syndrome pregnancies. The size of the primordial follicle pool at birth is determined by oogenesis and by the rate of follicle atresia during the intra uterine period. Since intra uterine growth retardation was reported to be associated with a significantly reduced primordial follicle pool at birth, we investigated the possibility of a relation between low birth weight for gestational age and the risk of a Down's syndrome pregnancy. In a case control study, 95 women with a history of a Down's syndrome pregnancy and 85 controls provided information on their own birth weight and length of gestation. Birth weight standard deviation scores, indicating the difference in birth weight from a reference group, were significantly lower in Down's syndrome mothers than in controls. These findings illustrate that the risk of a Down's syndrome pregnancy is related to a low birth weight corrected for gestational age, possibly by a causal relation between intra uterine growth retardation and the size of the primordial follicle pool.     

Mitotic disturbances associated with inversion 9qh. A case report

A 25-year-old female with history of spontaneous abortion and subsequent birth of Down syndrome child was referred for chromosome analysis. Her karyotype revealed 46, XX with pericentric inversion of 9 qh, while her husband was normal with 46, XY chromosomes. Metaphase analysis of the female showed 20.5% cells with premature centromere division, 4% with endoreduplication, 2% with polyploidy and 9.33% aneuploidy. These frequencies were considerably higher as compared to a normal control. These observations suggest that inv (9qh) might have some interchromosomal effect leading to higher incidence of mitotic disturbances, finally resulting in aneuploidy. This predisposition is evident by spontaneous abortion and later birth of a Down syndrome child.     

A survey on maternal age and karyotype in Down's syndrome in Japan, 1947–1975

Summary Data on karyotype and maternal age of 1954 cases of Down's syndrome were analyzed to see if the rate of chromosome mutations leading to this abnormality has been enhanced during the last 20 years. Comparison of the data for patients born in 1947–1960 with those in 1961–1975 revealed little change with time in the proportions of cases due to different karyotypes, the overwhelming majority being of 21 trisomy type in both periods. However, there has been a remarkable decline in the mean maternal age from 33.1 years to 29.7 years as well as in the variance from 50.5 to 29.4. While the rate of decline in the variance was almost the same as that for all births occurring in the same periods, the decline in the mean maternal age was much greater for the patients than for all births, suggesting that the rate of nondisjunction might have increased in younger rather than in older mothers. However, when the risk of brearing a child with Down's syndrome for mothers aged 40–44 is taken as unity, no evidence was found for an increase with time in the relative risk for younger mothers. Moreover, results of surveys made in 1960 and thereafter in different parts of Japan indicate that the crude incidence rate of Down's syndrome at birth has been around 0.10%, giving no indication of an upward trend. These findings are discussed with reference to the serious environmental pollution, including possible genetic hazards, with which Japan has been faced since the 1960s.     

Complex study of human cell strains with karyotype anomalies. II. Mitotic cycle parameters]

The object of this investigation were the parameters of the mitotic cycle in 14 fibroblasts-like cell strains with chromosome aberrations obtained from skin biopsies of patients and from spontaneous human abortuses. In two strains of embryonal origin (trisomic for chromosome and monosomic for chromosome 21) increased duration of stage G2 of the cell cycle accompanied by a shorter period of DNA synthesis was observed. In the other 5 strains of embryonal origin (two strains trisomic for chromosome 7, strains trisomic for chromosome 9, trisomic for chromosome 14 and triploid strains) no deviations from the normal duration of the stages of the cell cycle were observed. Two types of changes of the mitotic cycle parameters were observed in the cell strains obtained from patients with chromosome aberrations. A considerably prolonged G2 stage was observed in two strains obtained from patients affected by Down's syndrome. Three strains with the karyotypes 47, XXX, 47 XY+18 and 46, XX, 5p-were characterized by a complex of features typical of the strains of embryonal origin. A considerable decrease of the stage G2 duration was observed in these strains. In the strains obtained from a proband with Kleinfelter's syndrome and from a patient with the karyotype 46XX no deviations in the parameters of the cell cycle were observed.     

An infant with Turner-Down aneuploidy and massive capillary hemangioma of the orbit: a case report with review

We report on a case of double aneuploidy involving Down and Turner cell lines in a female child with a massive capillary hemangioma of the left orbit and mild clinical features of Down syndrome. Cytogenetic findings with G-banding revealed mosaicism in her peripheral blood, i.e. mos45,X[48]/47,XX,+21[28]/46,XX[12/47,XXX[12]. Mosaicism of such nature is rare and to our knowledge the present case is the first reported of Turner-Down double aneuploidy mosaicism associated with an orbital capillary hemangioma. An annotated bibliography of earlier reported cases with documented karyotyping is also included.     

Trisomy 6p22→6pter due to familial t(6;13)(p22;q34 or 33) translocation

Summary 235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.     

Reexamination of paternal age effect in Down's syndrome

Summary The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47,+21 cases was studied. The mean paternal age was 0.16 year greater than in the entire population of live births after controlling for maternal age. There was no evidence for a significant paternal age effect at the 0.05 level. For 242 of these Down's syndrome cases, control subjects were selected by rigidly matching in a systematic manner. Paternal age was the variable studied, with maternal age and time and place of birth controlled. There was no statistically significant association between paternal age and Down's syndrome. After adjustment for maternal age, these two studies were not consistent with an increase of paternal age in Down's syndrome.