A. Kleczkowska

The psychological profile of the fragile X syndrome

An attempt is made to present a more accurate description of the psychological profile of males with the fragile X syndrome after the evaluation of an unselected group of 21 affected patients. Except for one boy with slight mental retardation, all were moderately to severely mentally retarded, with retardation of motor development and pronounced speech disability. The most striking behavioral problem is hyperactivity together with concentration difficulties. A great number of patients show auto mutilation especially with hand biting, and autistic behaviour also appears in some of them.

Pericentric inversions in man: personal experience and review of the literature

SummaryThe Leuven cytogenetic centre experience on pericentric inversion in man is discussed with exclusion of the pericentric inversions of the heterochromatic blocks of chromosomes 1 and 9. In a total of 51,500 patients, referred for constitutional chromosome analysis during the period 1970–1985, pericentric inversions were found in 24 index patients. The breakpoints detected in these different pericentric inversions are summarized and compared to those found in previous reports. Bands 2p13, 2q21, 5q31, 6c21, 10q22, and 12q13 were shown to be repeatedly involved in the different studies and, furthermore, breakpoints at bands 2q11, 5p13, 5p15, 5q13, 7q11, 11q25, and 14p11 were present in this study as well as in our previous review on reciprocal autosomal translocations. In 13 familial pericentric inversions, even after exclusion of all inversion carrier probands, a 1.6:1 excess of pericentric inversion carriers versus karyotypically normal progeny was observed. While chromosomally unbalanced offspring represent 3.5% of all chromosomally investigated liveborns of the present study, 7.1% of all liveborn inversion carrier offspring presented with a mental retardation and/or multiple congenital anomalies (MR/MCA) problem. Additional chromosomal abnormalities, i.e. a 21 trisomy and an accessory small ring chromosome were observed in two pericentric inversion carriers. These data and results are discussed and compared to the data available in the literature.

X-chromosome polysomy in the male

SummaryA review of 569 male patients with X-chromosome polysomies (544 Klinefelter and 25 patients with other types of X-chromosome polysomy) is presented here. These patients were detected among the 77000 persons karyotyped in the Leuven cytogenetic center between the years 1966 and 1987. In the group of 544 Klinefelter patients special attention was paid to (1) the age at diagnosis, (2) social and marital status of the postpubertal males, (3) physical and intellectual abilities of the prepubertal boys, (4) delineation of the concurrence of Klinefelter syndrome and fragile X syndrome, and (5) the frequency of malignancies. In 25 patients with other X-chromosome polysomies (2 n≥48 chromosomes) genotype/phenotype correlation is reviewed, especially for the patients with 48,XXYY and 49,XXXXY karyotypes. Finally, double aneuploidy and rare structural X-chromosome aberrations are briefly discussed.

Cytogenetic survey in couples with recurrent fetal wastage.

SummaryCytogenetic 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.

The pathology of trisomy 13 syndrome

SummaryAnatomical and histopathological findings in 12 cases of trisomy 13 syndrome (nine with classic full trisomy and three with trisomy 13 and an unbalanced Robertsonian 13/13 translocation) are reported. Emphasis is on the brain defects, cardiovascular anomalies, and histological organ dysplasia. Eight patients showed abnormal development of the forebrain and midline facial structures (holoprosencephaly). Cardiovascular malformations were invariably present, the leading malformation being an infundibular ventricular septal defect often in combination with dextroposition of the aorta and abnormalities of the semilunar valves. Histological abnormalities giving evidence of organ dysplasia were observed in the central nervous system, eyes, pancreas, kidneys, and ovaries. Mild cystic renal dysplasia was a constant feature. Foci of persistent nodular renal blastema were found in six cases. The pancreatic dysplasia appears to be pathognomonic for trisomy 13. These observations illustrate the importance of pathological studies in the recognition of chromosome abnormalities and, more specifically, of trisomy 13 syndrome. Based on autopsy data, trisomy 13 can be diagnosed — or ruled out — with certainty, even in the absence of karyotyping.

Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents

Three achondroplastic sisters born to normal parents are reported. This report constitutes an unique example of germinal mosaicism in the human.

Distal 11q monosomy. The typical 11q monosomy syndrome is due to deletion of subband 11q24.1.

In this paper we describe two new patients with distal 11q monosomy and precisely localize breakpoints using high resolution banding techniques. The findings in these two patients further contribute to the precise localization of the crucial band for 11q monosomy syndrome as being at 11 q24.1. A very distal 11 q24.2 deletion in the second patient resulted in a completely different phenotype.

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

SummaryIn 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.

Trisomy of the short arm of chromosome 5: autopsy data in a malformed newborn with inv dup (5) (p13.1----p15.3).

In this paper we report detailed autopsy data of a malformed male newborn with Sp trisomy due to a de novo inverted 5p duplication, inv dup (5Xpl3.1→ pl5.3), and we compare these data with the findings in previous reports on 5p trisomy. Cerebral malformations, i.e. agenesis of corpus caliosum, and Dandy‐Walker cyst malformations, seem to be another characteristic finding in this partial autosomal duplication syndrome.

Fertility in patients with X chromosome deletions

Three fertile, non‐mosaic patients with partial monosomy of an X‐chromosome (two with Xp deletion with breakpoints at Xpl 106 and Xp2101, respectively, and one with a del(Xq25)) were found among 12 females with Xp deletion and three with Xq deletion investigated in this laboratory after the advent of banding techniques. Four phenotypically normal children resulted from a total of seven pregnancies in these women. Three of the children were chromosomally normal and one girl presented the same del(Xp) as her mother. The possibility of having genotypically and phenotypically normal offspring should be taken into account in the management and genetic counseling of children and females with X‐chromosome deletions.