Mary Puck

Pituitary-gonadal function in Klinefelter syndrome before and during puberty.

ABSTRACT: Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropinreleasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

Dyslexia in 47,XXY boys identified at birth.

The 47, XXY karyotype has been associated with diminished language skills in the presence of average intelligence, but specific deficits in cognitive abilities have not been clearly and consistently established. The present study examined cognitive skills in 14 unselected 47,XXY boys (ages 8 to 18 years) and 14 euploid control boys matched for age and socioeconomic status. No significant differences were found on measures of intelligence, perception, and language, although mean score trends suggested mildly diminished skills in these areas. The 47,XXY group demonstrated significantly poorer auditory short-term memory and reading skills. One-half of the propositi exhibited a common constellation of deficits suggesting that their karyotype may represent a risk factor for a language-based dyslexia with primary features including deficits in memory and speed of processing. Small sample size necessitates caution in making generalizations which await verification from other studies of unselected 47,XXY boys. Possible biological mechanisms responsible for neurocognitive variations in children with sex chromosome anomalies have been hypothesized, but evidence for their existence remains elusive.

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.

Genetic counseling: an appraisal

From personal interviews with former consultands, we have learned much about the effectiveness and impact of our genetic counseling services during the past decade. Counseling has been well received and understood by most recipients. Consultands make rational decisions regarding family planning in post‐counseling years. Factors have been identified which limit the effectiveness of genetic counseling. Former counselees are valuable critics, offering excellent suggestions for improving service, many of which have been incorporated into our current procedures. Continued follow‐up of patients and evaluation of results are necessary concomitants of a successful genetic counseling program.

Intrauterine diagnosis: Potential complications

The hazards of amniocentesis for intrauterine diagnosis have yet to be established. We are particularly concerned by the high incidence (7.5 per cent) of postamniocentesis abortions and amniotic fluid leaks in our series. A larger experience is certainly needed before these concerns can be disregarded. Until then, it is important that indications for this procedure be strictly adhered to.

Early childhood development of four boys with 47, XXY karyotype.

In an epidemiological study, infants identified at birth as having sex chromosome anomalies are enrolled in a voluntary, long term evaluation program. Case histories are presented of the first four boys in the series to have a 47, XXY karyotype. They have been followed from birth for 6 to 9 years, with physical and psychological evaluations. Parents were informed in general terms of the childs genetic defect, and were offered continuing support and encouragement throughout the study. Close cooperation with the families was maintained. So far, the development of all these children has fallen clearly within the normal range and a reasonable healthy developmental pattern has been secured. Minor deviations in motor, speech and emotional development suggest a common underlying pattern, but four cases are too few on which to establish a relationship between karyotype and phenotype. The data suggest that the symptomatology reported in selected children with a 47, XXY karyotype may be strongly dependent on factors other than the chromosomal constitution, and that an appropriate familial and environmental situation may minimize elevated risks due to the marked genetic defect.

Short Communication: Skeletal Maturation of Children with Sex Chromosome Abnormalities

Summary: Skeletal maturity, or “bone age,” is one of the several criteria used to determine developmental or physiologic age as opposed to chronologic age. The purpose of this study of skeletal maturation of children with sex chromosome abnormalities (45,X, 47,XXX, 47,XXY, X-chromosomal mosaics) and controls is 2c-fold: (1) to investigate if children with sex chromosome aneuploidy ascertained in an unbiased fashion differ in skeletal maturation from their siblings and other normal healthy children born in Denver, Colorado, and (2) to assess if the skeletal age standards currently in use (Greulich-Pyle; Tanner-Whitehouse) are applicable to Denver children when evaluating radiographs for skeletal maturation. Mean chronologic and skeletal age were measured. Mean differences between skeletal and chronologic age for all groups across all measures were calculated.The 45,X females constitute the only group studied with bone ages lower than expected (0.05 > P > 0.01; two-tailed test). We found no other significant differences in skeletal maturation between Denver children with sex chromosome abnormalities and their siblings or the control sample of Denver children.Although we found the Tanner-Whitehouse standards to be more applicable for use with this population, all the Denver groups investigated yielded consistently lower bone ages than expected published norms.This is the first documentation in a group of children with sex chromosome abnormalities, ascertained in an unbiased fashion, that, with the exception of those with a 45,X karyotype, bone age is not significantly different from that of the normal population.

Intra-uterine diagnosis of birth defects.

One of the major long term aims of teratology, I presume, is the prevention of birth defects by increasing our knowledge of extrinsic factors which interfere with normal fetal development. It may be appropriate to remind you that another way to prevent birth defects is to interrupt pregnancy when there is evidence of fetal maldevelopment.

EARLY CHILDHOOD DEVELOPMENT OF FOUR BOYS WITH 47,XXY KARYOTYPE

Infants identified at birth in an epidemiological study of sex chromosome anomalies are enrolled in a voluntary long-term evaluation program. Case histories of the first four boys in the series with 47, XXY karyotype are presented. They have been followed from birth for six to nine years with regular and frequent physical and psychological evaluations. Close cooperation with the childrens parents was maintained to provide families with supportive consultation. Results demonstrate that their development so far clearly falls within normal range. Minor deviations in motor, speech, and emotional development suggest a common underlying pattern, although four cases are too few on which to establish a relationship between karyotype and phenotype. The data, however, suggest that symptomatology which has been reported in selected children with a 47, XXY karyotype may be strongly dependent on factors other than the chromosomal constitution, and that appropriate environmental sustenance may minimize elevated risks due to the marked genetic defect.