Gross and fine motor development in 45,X and 47,XXX girls.

Neuromuscular deficits have been described in 47,XXY and 47,XYY boys, but gross and fine motor development of girls with sex chromosome aneuploidy has not been extensively studied. Twenty-one propositae 8 to 19 years of age, identified through newborn screening to be 45,X, 47,XXX, or 45,X mosaic, and 11 control girls were evaluated by a physical therapist unaware of their genetic constitution. The Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) was administered, and the quality of neuromuscular function was determined. The 45,X and 47,XXX propositae exhibited both gross and fine motor dysfunction, with 12 of 15 BOTMP composite scores below the 10th percentile. The clinical assessment confirmed the BOTMP findings, with 13 propositae exhibiting dysfunctional sensory-motor integration. A delay in the age of independent walking confirmed the consistency of motor developmental dysfunction throughout time. Sex chromosome mosaics were more similar to control girls. The gross and fine motor delays were frequently associated with a moderate to severe language dysfunction which adversely affected classroom performance. Regular developmental assessments of children with sex chromosome aneuploidy, including sensory-motor integration, should assist in the identification of early developmental delays and permit appropriate intervention.

Gross and fine motor development in 47,XXY and 47,XYY males.

Neuromuscular deficits described in early childhood as motor awkwardness or slow movements are still clinically present in school-aged boys with XXY and XYY sex chromosome aneuploidy. A control group of 14 boys (6 to 19 years of age) and 14 XXY and four XYY boys (6 to 15 years of age), identified by newborn screening, were blindly evaluated by a physical therapist. The Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) was administered and a clinical rating of neurologic status and sensory-motor integration was assigned. On the motor proficiency test, the XXY boys had significantly lower mean scores for upper limb coordination, speed and dexterity, and on gross motor and battery composites. The neuromuscular status of the aneuploid boys was deficient, with hypotonia, apraxia, primitive reflex retention, and problems with bilateral coordination and visual-perceptual-motor integration. This mild to moderate dysfunctional sensory-motor integration, as well as previously described auditory-processing deficits and dyslexia, contributed to school performance below that expected from their cognitive potential.

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.

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.