XYY syndrome and other Y chromosome polysomies. Mental status and psychosocial functioning.

In this report we review the data on 75 male patients with extra Y chromosome diagnosed in Leuven in the period 1968-1993 among 98,725 patients (males and females) referred for constitutional chromosomal analysis. Special attention was given to their mental performance and psychosocial functioning. 1. Fifty male with 47,XYY karyotype were diagnosed. This is very close to the incidence of XYY in newborn studies and indicates that the frequency of MR/MCA is not increased in XYY male in general. 2. In the 60 patients with "pure" Y chromosome polysomy, the most frequent indication for karyotyping was the presence of MR and/or characterological problems in the index patients. Mental retardation was mostly borderline to mild, and severe mental retardation was rare. Characterological problems, difficulties in psychosocial integration and psychiatric problems were found in 86% of the mentally retarded versus 24% of the mentally normal men. 3. The 48,XXYY syndrome is characterized by markedly frequent and severe behavioural and psychiatric problems.

On the excess of mental retardation and/or congenital malformations in apparently balanced reciprocal translocations. A critical review of the Leuven data 1966-1991.

In this report we review 286 reciprocal translocations (rcpt) diagnosed in Leuven in the period 1966, mid 1991. They were selected from a total number of 82,000 patients karyotyped for constitutional reasons. Special attention is paid to: (1) the phenotypic effect of de novo reciprocal chromosomal rearrangements and (2) the incidence of mental retardation/congenital malformations (MR/CM) in familial rcpt. Important conclusions of this study were: 1) The high incidence of MR/CM in de novo rcpt, not only in patients with complex chromosomal rearrangements (greater than 80%) but also in patients with classical two breaks rcpt (greater than 60%). In contrast, the phenotypic effect of normal/mosaic rcpt seems to be minimal. 2) The overall incidence of MR/CM in carriers of familial balanced rcpt was 6.4%. Interestingly, the incidence of MR/CM problems in rcpt carriers from families detected because of reproductive failure was not increased (2.3%). However, the risk to find MR/CM in a rcpt carrier was much higher (12.8%) if he/she belonged to a family in which the rcpt was detected in an index patient with MR/CM.

Cytogenetic findings in a consecutive series of 478 patients with Turner syndrome. The Leuven experience 1965-1989.

In this report, we present the cytogenetic findings in 478 patients with Turner syndrome diagnosed in Leuven in the period 1965-1989. The karyotypic anomalies are classified into seven groups: 1) classic, 45,X karyotype (52.1%); 2) mosaic 45,X/46,XX (10.9%); 3) mosaic 45,X/47,XXX and other "super-female" cell lines (4.6%); 4) isochromosomes i(Xq) and i(Xp) (16.1%); 5) ring chromosomes r(X) (4.4%); 6) other structural aberrations of the X chromosome (7.7%); and finally 7) mosaic 45,X/46,XY patients (4%). The most pertinent chromosomal findings are briefly discussed and compared with previous reported surveys on subject.

Turner syndrome: the Leuven experience (1965-1989) in 478 patients. I. Patient's age at the time of diagnosis in relation to chromosomal findings.

Within the past 25 years 478 patients with Turner syndrome have been diagnosed in the Leuven Centre for Human Genetics. After exclusion of 36 lost pregnancies, mostly first trimester spontaneous abortions, almost 20 per cent of the remaining 442 Turner syndrome patients have been early detected, i.e. before the age of two years. Moreover, a high prevalence of classic 45,X karyotype over other karyotypes was observed in this age group. The high mortality of prenatally diagnosed Turner syndrome fetuses is discussed here in view of the most common associated congenital malformations.

Turner syndrome: II. Associated anomalies, mental performance and psychological problems in 218 patients diagnosed in Leuven in the period 1965-1989.

Selected medical and psychosocial problems in 218 Turner syndrome patients diagnosed at the Leuven Centre for Human Genetics are reported here. Special attention is paid to the associated congenital malformations, the mental performance and the occurrence of psychosocial and/or characterological difficulties. Mental underdevelopment was documented in 50 patients (22.9 per cent) and psychosocial and/or characterological problems in a total of 44 patients (20.2 per cent). This study confirms that in patients with Turner syndrome diagnosis special attention should be drawn to the mental development and psychosocial problems.

[Structural chromosomal rearrangements in couples with repeated miscarriages. Experience in Louvain]. / Réarrangements chromosomiques structurels chez des couples avec fausses-couches à répétition. L'expérience à Leuven.

In this paper we report our experience in the cytogenetic study of 1555 couples with recurrent first trimester fetal wastage. The frequency of chromosomal anomalies was found to be 6.36%, the majority of then (greater than 50%) being autosomal reciprocal translocations.

Excess of mental retardation and/or congenital malformation in reciprocal translocations in man.

In this report the Leuven experience (1970-1984) on reciprocal translocations is summarized. A total of 153 unrelated index patients, carriers of different types of reciprocal translocations, and their families were investigated. Familial reciprocal, apparently balanced translocations were found in 75 unrelated families bringing the total numbers of translocation carrier parents and their offspring to 132 and 445, respectively. In 61.5% of the patients the reciprocal translocation was detected after the birth of a malformed child with unbalanced karyotype or through investigation because of recurrent spontaneous abortions, stillbirths, or infertility. In 41 patients (28 familial and 13 de novo), however, the reciprocal balanced translocation was found to be associated with mental retardation and/or congenital malformations (MR/CM) which is significantly higher than expected. This excess of MR/CM in de novo and familial balanced translocation carriers is illustrated and discussed.

Cytogenetic findings in moderate and severe mental retardation. A study of an institutionalized population of 1991 patients.

The cytogenetic data of a large scale study in an institutionalized population of 1991 moderately and severely mentally retarded patients are presented. In 21.3% of these patients a chromosomal aberration was diagnosed (14.9% Down syndrome patients and 3.5% "other chromosomal anomalies"). A fragile X screening was performed in 354 males, and was found to be positive in 57 (16.1% positive). Different chromosomal variants were present in another 6% of this population. Detailed results are presented on the different groups of chromosomal aberrations.

Cytogenetic survey in couples with recurrent fetal wastage.

Cytogenetic studies have been performed in 1068 couples with antecedent fetal wastage, i.e., at least two spontaneous first trimester abortions or one spontaneous first trimester abortion and one late fetal death, particularly with multiple congenital malformations. Three major types: 33 reciprocal translocations (3.09%), 20 Robertsonian translocations (1.87%) and six other chromosomal abnormalities (0.56%) were found, bringing the total number of chromosomal abnormalities to 59 (5.5%) in 1068 couples under investigation. In contrast to couples with reciprocal translocations, a high excess of female over male carriers was found in the group of Robertsonian translocations. In the evaluation of chromosomal polymorphisms, only variants with particularly large paracentromeric constitutive heterochromatin blocks were taken into account, and their low frequency in the present study is therefore not comparable with that in a general population. The impact of further extensive familial investigation on genetic counseling and the follow-up of prenatal diagnosis are discussed.

Inactivation pattern of the fragile X in heterozygous carriers.

Chromosome analysis with conventional staining, G-banding, and R-banding with 5-bromodeoxyuridine (BrdU) incorporation were performed on the lymphocytes of ten females, who were heterozygous for the fragile X-chromosome. Mental development of these females varied greatly: moderate to severe mental retardation was found in one and moderate mental retardation in four females. Normal to borderline intelligence was found in three and normal intelligence was noted in two further females. The discrepancy in percentage of active fragile X-chromosomes in the five females with moderate mental retardation was found to be 60-100% (mean value: 80%). The three women with normal to borderline intelligence showed a corresponding discrepancy from 57 to 86% (mean value: 77%) of active fragile X-chromosomes. Finally, two female heterozygotes for fragile X with normal intelligence showed 70 and 76% (mean value 73%) of active fragile X-chromosomes. The phenotypic features also did not seem to correspond with the X-chromosome inactivation pattern. Based on the data obtained, we suggest that there is no evident correlation between the frequency of the active fragile X chromosomes and the mental status of these females.

Ring chromosome 14. A distinct clinical entity.

In this report two non consanguineous children are presented with strikingly similar phenotypes confirming the existence of a characteristic phenotype due to a ring chromosome 14 formation.

XY/XXY mosaicism and fragile X syndrome.

Clinical and cytogenetic data of a XY/XXY mosaic Klinefelter patient with fragile X are presented.

Familial translocation t(lp--;21q+) associated with Down's syndrome.

Familial occurrence of 1/21 translocation in connection with trisomy 21 was described. The possibilities of inheritance of further chromosome rearrangements arising during the gametogenesis of persons with this translocation were considered.

Familial occurrence of chromosome variant 17ph+.

A structural chromosome variant 17ph+ was found in a high genetic risk family. The authors consider the possibility of a causal connection between minor structural changes in the karyotype and congenital defects appearing in one member of the family.