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

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 gonadotropin-releasing 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.

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 child's development.

Parents' adaptation to early diagnosis of sex chromosome anomalies.

In 56 structured psychiatric interviews parents were asked to describe their experience as participants in the Denver prospective study of children with sex chromosome anomalies in order to assess its impact on attitudes toward the identified child and on family relationships. It was found that most achieved satisfactory understanding of the diagnosis with minimal disturbance, preferred early disclosure, denied its influence on parent-child and parent-parent relationships, and were reasonably comfortable in sharing diagnostic information with the child. Environmental and cultural factors did not correlate with the responses obtained. Emphasis directed toward obstacles in the adaptive process permitted evaluation of reported parental anxieties arising from faulty or delayed communication of the diagnosis, a child's adjustment to problems of growth and development, and, for parents of children with 45,X and 47,XXY chromosome constitutions, anxiety regarding anticipated difficulty in sexual maturation and fertility. The assessment interviews afforded additional opportunity for clinical discussion and counseling with parents on issues of concern to them.

Short communication: skeletal maturation of children with sex chromosome abnormalities.

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 greater than P greater than 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.

Development of eight pubertal males with 47,xxy karyotype.

The increasing frequency with which the diagnosis of the 47,XXY karyotype is made requires more knowledge of the prognosis of this condition. We present four 47,XXY boys identified at birth and followed since then (Group I), and four 47,XXY boys diagnosed because of physical and/or emotional problems (Group II). Physical, psychological, language, and hormone data are presented. The physical and intellectual profiles for the two groups are similar. This is in contrast to the very poor school and emotional adjustment of the Group II individuals. These boys were definitely more difficult and problematic for their parents when compared to their siblings and to Group I who were unselected. This further emphasizes that the expression of this karyotype is variable and individuals with behavioral disorders may represent a maladaptive subgroup rather than the entire population of 47,XXY males. Recommendations are given for intervention with attention to learning and language problems, hormone status, and emotional state.

Some considerations bearing on the doctrine of self-fulfilling prophecy in sex chromosome aneuploidy.

The doctrine of self-fulfilling prophecy has been invoked in studies of the effects of sex chromosome aneuploidy on human development as a reason for routine concealment of the diagnosis from affected children and their families. It has been assumed that knowledge of the existence of risk for deviance from normal development automatically creates a self-defeating emotional climate. This communication attempts to delineate both advantageous and deleterious aspects of self-fulfilling prophecy in the medical management of sex chromosome aneuploidy, present at alternative approach, and reviews the experience in a prospective study of 52 families where a policy of disclosure was followed.

Genetic counseling: an appraisal.

PIP: To assess the impact of genetic counseling interviews with former recipients of the counseling (consultands) in the Genetic Counseling Clinic of the University of Colorado were conducted. It was found that the interviews, as compared with questionnaire alone, with 87 couples provided the best insights and interchange of ideas. A correlation was established between social class, which included educational levels, and understanding but no correlation between understanding and degree of risk. The majority of consultands retained the information over extended periods of time. Over 1/2 of the consultands (56 of 101) found the counseling helpful. A positive correlation existed between the degree of satisfaction and level of understanding. 41 couples were influenced in their family planning by the genetic counseling. Genetic counseling was of limited effectiveness when the counselor was unable to satisfy the expectations of the consultand for enlightenment about the cause of problems, particularly those of unknown etiology. Counselees' most frequent suggestion for improved effectiveness was to expand knowledge about the availability of counseling services. They also felt that 3-6 months were needed for couples to adjust to the discovery of a birth defect before counseling information could be assimilated.^ieng