Down syndrome: progress in research.

This review discusses the research published in the last five years on the behavioral, genetic, medical, and neuroscience aspects of Down syndrome. The subject areas that have experienced the most active research include Alzheimer disease, language development, leukemia, and pregnancy screening and diagnosis. These and other areas are reviewed.

Etiology of hearing loss in children. Nongenetic causes.

Every child with a hearing loss should have an evaluation to determine the cause of hearing loss. This article focuses on the nongenetic origins of hearing loss, the most frequent of which is the neonatal intensive care unit experience, followed by meningitis, cytomegalovirus, and other infections. Preventable causes such as exposure to ototoxic medications and noise are also discussed in this article.

Acquisition of services recommended by a multidisciplinary medical diagnostic team for children under three years of age evaluated for developmental delays.

After multidisciplinary medical diagnostic teams evaluate children with developmental delays, they recommend to parents that they seek specific services, but the team rarely knows which services are obtained. We sought to determine which services pursued by the parents were actually acquired and to determine if there were barriers to the acquisition of services. In a diagnostic clinic located in a teaching hospital in an urban setting, we evaluated 92 children less than 3 years of age mainly from an inner city population. At a family conference, the parents had indicated an interest in pursuing an average of 1.87 +/- 1.34 social services, 1.70 +/- 1.32 educational services, and 3.61 +/- 2.31 medical services recommended by the team. Four months after the family conference, the actual services obtained by families included 38.5% of the social services, 70.87% of the educational services, and 71.36% of the medical services. Significantly fewer social services were obtained than educational and medical services.

Nutrient intake and obesity in prepubescent children with Down syndrome.

OBJECTIVE: The aim of this study was to measure nutrient intake and body composition in prepubescent children with Down syndrome to understand dietary barriers involved in the prevention and treatment of obesity. DESIGN: Dietary intake was determined from parent-reported 3-day diet records for children with Down syndrome and control subjects. Energy intake was compared with energy expenditure measured by the doubly labeled water method. Body composition was determined by deuterium dilution, bioelectrical impedance analysis, and skinfold thickness measurements. SUBJECTS/SETTING: Ten prepubescent children with Down syndrome and 10 control subjects were recruited from the hospital community. The study was conducted in the Clinical Research Center of the University of Chicago Medical Center. MAIN OUTCOME MEASURES: Nutrient intakes were compared with the Recommended Dietary Allowances (RDAs) to estimate risk for nutrient deficiency. Fat-free mass values determined by bioelectrical impedance analysis and measurement of skinfold thicknesses were compared with values determined using the deuterium dilution method. STATISTICAL ANALYSES PERFORMED: Unpaired t tests were used for comparisons between subjects groups and the Wilcoxon signed-rank test was used for comparison of nutrient intakes with RDAs. RESULTS: The subjects with Down syndrome were significantly shorter (P < .01) than control subjects; however, body composition did not differ between the groups. Reported energy intake was lower in subjects with Down syndrome. In addition, several micronutrients were consumed, especially among nonobese subjects with Down syndrome, at less than 80% of the RDA. APPLICATIONS: To avoid lowering already inadequate intakes of several vitamins and minerals, we suggest that treatment of obesity in children with Down syndrome combine a balanced diet without energy restriction, vitamin and mineral supplementation, and increased physical activity.

Methylphenidate dosing: twice daily versus three times daily.

OBJECTIVE: To evaluate the short-term efficacy and side effects associated with two methylphenidate hydrochloride (MPH) dosing patterns. METHODS: Twenty-five boys with attention deficit hyperactivity disorder (ADHD) participated in a 5-week, triple-blind, placebo-controlled, crossover evaluation of MPH administered twice (b.i.d.) versus thrice (t.i.d.) per day (mean dose = 8.8 +/- 5 mg, .30 +/- .1 mg/kg/dose). Four dosing conditions (placebo, titration [gradual increase to target dose], b.i.d., and t.i.d.) were used. Dependent measures obtained on a weekly basis included: parent and teacher ratings of child behavior, parent-child conflicts, parent report of stimulant side effects, child self-report of mood symptoms, a sleep log, laboratory measures of attention, and actigraphic recording of sleep activity. RESULTS: All dosing conditions resulted in significant effects on ADHD symptoms when compared with baseline. Relative to placebo, t.i.d. dosing was characterized by improvement on the greatest number of behavioral measures, and both b.i.d. and t.i.d. were generally more effective than titration. Direct comparisons of b.i.d. and t.i.d. dosing revealed that t.i.d. was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor, with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor. The analysis of clinically significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention. Compared with placebo, appetite suppression was rated, on average, as more severe in the t.i.d. and titration conditions, but not in the b.i.d. condition. However, the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d. and t.i.d. schedules. Although there was no difference in sleep duration for children on b.i.d. and t.i.d. schedules, total sleep time appeared to decrease slightly on t.i.d. relative to placebo according to both parent ratings and actigraphic assessment. There were no significant differences between b.i.d. and t.i.d. on any other side effects or sleep variables. CONCLUSIONS: For many children with ADHD, t.i.d. dosing may be optimal. There are few differences in acute side effects between b.i.d. and t.i.d. MPH dosing. The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects.

Resolution of intracranial calcifications in infants with treated congenital toxoplasmosis.

PURPOSE: To determine the natural history of intracranial calcifications in infants with treated congenital toxoplasmosis. MATERIALS AND METHODS: Between January 1982 and March 1994, cranial computed tomography was performed in 56 infants with treated congenital toxoplasmosis when they were newborns and approximately 1 year old. Locations and sizes of intracranial calcifications were noted. RESULTS: Forty newborns had intracranial calcifications. By 1 year of age, calcifications diminished or resolved in 30 (75%) and remained stable in 10 (25%) of these treated infants. Ten (33%) of the 30 infants whose calcifications diminished versus seven (70%) of the 10 infants with stable calcifications received less intensive antimicrobial treatment than the other treated infants. In contrast, a small number of infants who were untreated or treated 1 month or less had intracranial calcifications that increased or remained stable during their 1st year of life. CONCLUSION: Diminution or resolution of intracranial calcifications was an unexpected and remarkable finding in infants with treated, congenital toxoplasmosis, consonant with their improved neurologic functioning.

Psychiatric and developmental disorders in families of children with attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate whether a pediatric family history obtained via a brief parent interview would reveal a high prevalence of psychiatric and developmental disorders in the family members of children with attention-deficit hyperactivity disorder (ADHD) compared with a group of children with another chronic developmental disability, Down syndrome (DS). DESIGN: A controlled cross-sectional group comparison study. SETTING: An interdisciplinary hyperactivity and learning problem clinic and a DS clinic located in a large, urban tertiary care teaching hospital in Chicago, Ill. PARTICIPANTS: A total of 140 children with ADHD and 163 children with DS of comparable socioeconomic status. MEASURES: Using a screening questionnaire and parent interview, the development pediatricians obtained a family history. RESULTS: By parent report, children with ADHD were significantly more likely than the control children with DS to have a parent affected by alcoholism (P = .007), other drug abuse (P < .001), depression (P < .001), delinquency (P < .001), learning disabilities (P < .001), and ADHD (P < .001). Similar patterns were evidenced in other first- and second-degree relatives. CONCLUSIONS: The high reported frequency of psychiatric and developmental disorders in the families of children with ADHD requires that the treating clinician explore the area of family psychiatric and developmental history and use the findings to formulate a comprehensive treatment plan that includes anticipatory guidance and psychosocial intervention.

Adaptive skills dysfunction in ADD and ADHD children.

Adaptive functioning was examined in children with Attention Deficit Hyperactivity Disorder (ADHD) or Attention Deficit Disorder (ADD), and a psychiatric comparison group of children with pervasive developmental disorders or mild mental retardation (PDD/MR). As assessed with the Vineland Adaptive Behavior Scales, adaptive functioning was well below average for all three clinic groups. (The PDD/MR group had the lowest adaptive functioning scores, although not statistically different from the other groups). However, the level of adaptive functioning relative to IQ in the areas of Socialization, Communication and Daily Living was significantly lower for the ADD and ADHD groups. These deficits in adaptive functioning that characterize children with ADHD and ADD may help explain the poor long-term prognosis of ADHD, suggesting that increased attention should be paid to the assessment and treatment of adaptive functioning in individuals with ADHD and ADD.

Energy expenditure in children with Down syndrome: correcting metabolic rate for movement.

Children with Down syndrome (DS) have a high prevalence of obesity. To investigate the relation between energy expenditure and obesity, we measured body composition, resting metabolic rate (RMR), and total energy expenditure in 13 prepubescent children with DS and in 10 control subjects matched for age, weight, and percentage of fat, using indirect calorimetry and the doubly labeled water method. Measurement of RMR was complicated by excessive movement by both the DS and control subjects. We therefore developed a method of subtracting the energy expended in movement and calculated the corrected RMR. The corrected RMR was significantly lower in those with DS than in control subjects when expressed as a percentage of the basal metabolic rate, predicted by the World Health Organization: 79.5% +/- 10.4% and 96.8% +/- 7.8%, respectively (p < 0.001). No significant differences were detected in total daily energy expenditure or non-RMR expenditure between the subject groups. In the DS group, 60% of the variability in fat mass could be accounted for by non-RMR expenditure expressed per kilogram of body weight (p < 0.02). No relation was detected between fat mass and non-RMR expenditure in control subjects, nor were any measures of energy expenditure predictive of changes in fatness among the subjects with DS during a 1-year follow-up. The results of this study indicate that prepubescent children with DS have decreased RMR compared with control children.

Adaptive functioning in children with attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the utility of the Vineland Social Adaptive Scale (Vineland) in measuring social adaptive functioning in children with attention-deficit hyperactivity disorder (ADHD). DESIGN: Cross-sectional group comparison. SETTING: Multidisciplinary hyperactivity and learning problem clinic at a tertiary referral center in Chicago, Ill. PARTICIPANTS: One hundred four school-age children with ADHD. INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: The Vineland was administered to the study population. Despite average full-scale IQ scores (mean [+/- SD], 101 +/- 6), the children with ADHD had Vineland standard scores in the borderline to low-average range (73 +/- 14). The discrepancy between the Vineland standard scores and the full-scale IQ scores increased with increasing age and IQ. CONCLUSIONS: Children with ADHD referred to a tertiary attention problem clinic displayed significant social adaptive dysfunctioning on the Vineland. The evaluation of children with ADHD should include assessment of adaptive skills, and treatment planning for children with ADHD should include the identification of social and adaptive deficiencies when therapeutic goals are established.

Ophthalmic disorders in children with Down syndrome.

The goal of this study was to determine the frequency of ophthalmic disorders in a group of young children with Down syndrome who were unselected for ophthalmic abnormalities, and to determine whether examination by a pediatric ophthalmologist should become standard practice. Of 77 children referred to a Down syndrome clinic at a teaching hospital and evaluated by a pediatric ophthalmologist, 61 per cent had ophthalmic disorders needing treatment and monitoring. Furthermore, the percentage of children with ophthalmic disorders increased with age, from 38 per cent in the two- to 12-month-old group to 80 per cent in the five- to 12-year-old group. The authors conclude that children with Down syndrome should be evaluated by a pediatric ophthalmologist in the first six months of life and annually thereafter.

Sclerosis of the mastoid air cells as an indicator of undiagnosed otitis media in children with Down's syndrome.

We hypothesized that many children with Down's syndrome have undiagnosed otitis media. In a 1989 study of lateral neck radiographs of 22 children with Down's syndrome, we found that 64% had sclerosis of the mastoid air cells, indicating untreated or inadequately treated otitis media. We reviewed the lateral neck radiographs of 53 children with Down's syndrome and interviewed their parents regarding the diagnosis of otitis media. Mastoid air cells were found to be sclerotic in 22 (42%) of study subjects; 32% of these had no known history of otitis media. For the 68% of children diagnosed as having had otitis media, the most common symptoms were fever (61%) and cough or coryza (58%). Sclerosis of the mastoid processes was not associated with a high frequency of otitis media (> 20 episodes) or a higher frequency of hearing loss, but was associated with subsequent myringotomy and insertion of a ventilatory tube (P = .038). Our finding of sclerotic mastoids in 42% of children with Down's syndrome raises the possibility that children with Down's syndrome have unidentified or inadequately treated episodes of otitis media.

Depressive and obsessive-compulsive symptoms in hyperserotonemic parents of children with autistic disorder.

Because of previous findings that parents of children with autistic disorder may be at increased risk for anxiety disorders and/or mood disorders, the Center for Epidemiological Studies-Depression (CES-D) Scale and the Modified Maudsley Obsessive-Compulsive Inventory (MMOCI) were administered to parents of children with autistic disorder and parents of children with Down's syndrome. Parents with normal whole blood serotonin levels who had children with autistic disorder and parents of children with Down's syndrome had significantly lower CES-D depression scores than parents with elevated whole blood serotonin levels who had children with autistic disorder. Hyperserotonemic parents of children with autistic disorder had significantly higher MMOCI scores than parents of children with Down's syndrome.

Early maturation of motor-delayed children at school age.

Children underwent motor and sensory testing during each of 3 consecutive years beginning at kindergarten entrance. Children were assigned to either a motor-normal or motor-delayed group based on results from testing during the 1st year of the study. Motor-normal subjects (n = 17) had standard scores on a global motor-sensory test that fell within one standard deviation of the mean. Motor-delayed subjects (n = 12) had a global motor-sensory test standard score indicating greater than one standard deviation of motor delay and, in addition, were delayed by a minimum of one standard deviation on four of five of the motor-sensory test subtests. At the conclusion of the 3-year study, the mean standard score of the motor-delayed group remained greater than one standard deviation below the performance of the motor-normal group as measured by the global motor-sensory test. Statistical analysis using repeated measures analysis of variance indicated that the motor-delayed group made gains but did not close the gap between themselves and the motor-normal group during the 3-year study. Group x time interaction effects showed that during the study, significant gain was made by the motor-delayed group on the motor coordination subtest of the motor-sensory test. The study supports the conclusion that motor-delayed children without early intervention fail to outgrow their motor delays by age 8 years.

Hearing loss in children with Down syndrome.

Conventional behavioral testing of hearing shows that children with Down syndrome have a high prevalence of hearing deficits. However, most young (< 3.5 years of age) children with Down syndrome are unable to cooperate in this type of testing. We evaluated auditory brain-stem responses of 47 unselected patients 2 months to 3 1/2 years of age. Thirty-four percent had normal hearing, 28% had unilateral loss, and 38% had bilateral loss. Type of loss was conductive in 19 ears, mixed in 14, and sensorineural in 16. Degree of loss was mild in 33 ears, moderate in 13, and severe to profound in 3. Language quotients and degree of hearing loss were compared and an association was not found. Because of the high prevalence of hearing loss in children with Down syndrome, we recommend evaluation of auditory brain-stem responses in the first 6 months of life.

Hematologic abnormalities in children with Down syndrome.

We compared the hematologic parameters of 18 otherwise healthy children with Down syndrome (DS) in the age range of 2-6 years to those of 18 healthy non-DS controls matched for age and gender. The children with DS had MCVs and hematocrits increased significantly compared to controls and decreased WBCs compared to controls; 66% of the children with DS compared to 11% of non-DS controls had MCVs greater than the 97th percentile for age (P < 0.0001); the mean MCVs were 86.9 and 80.6, respectively. Although hematocrits were within normal limits for age for all DS and non-DS subjects, the DS patients had significantly higher hematocrits (39.1% vs. 36.9%, P < 0.014). We also found that 33% of the children had WBCs < 5% for age compared to 6% of controls. To determine whether folate deficiency contributed to these observations, we measured serum and RBC folate concentrations: these were not significantly different between the 2 groups. We conclude that macrocytosis and leukopenia are common in children with DS.

Hypoplastic posterior arch of C-1 in children with Down syndrome: a double jeopardy.

Radiographs of 38 children with Down syndrome (aged 2-3 years) were retrospectively evaluated for hypoplasia of the posterior arch of the C-1 vertebra. The anteroposterior dimensions of the posterior arch of C-1 were measured and compared with those of an age- and sex-matched control group. The posterior arches of C-2 to C-5 were similarly evaluated. Radiographs demonstrated hypoplasia of the posterior arch of C-1 in 26%. This anomaly of C-1 was an isolated event; sagittal diameters of C-2 to C-5 were within normal limits compared with those of the control group and published standards. Because of the known, potentially devastating atlantoaxial dislocation in Down syndrome, the increased prevalence of a second C-1 anomaly causing preexistent narrowing of the vertebral canal is of clinical concern. A hypoplastic posterior arch of C-1 may amplify the risk of spinal cord damage following atlantoaxial subluxation, as the subsequently smaller vertebral canal has less room for dorsal movement of the odontoid process. This potential "double jeopardy" of C-1 vertebral abnormalities should be recognized and assessed on cervical spine screening radiographs in children with Down syndrome.

Mastoid abnormalities in Down syndrome.

Hearing loss and otitis media are commonly associated with Down syndrome. Hypoplasia of the mastoids is seen in many affected children and sclerosis of mastoid bones is not uncommon in Down syndrome. Awareness and early recognition of mastoid abnormality may lead to appropriate and timely therapy, thereby preserving the child's hearing or compensating for hearing loss; factors which are important for learning and maximum development.

Cerebral palsy. A pediatric developmentalist's overview.

Exploration of the history, terminology, and classification of cerebral palsy reveals it as a complex entity. Criteria exist that may make early diagnosis and appropriate intervention possible. Dealing with patients who have cerebral palsy requires recognition of the associated problems and deficits. Comprehensive management usually requires a multidisciplinary setting, which is used to outline the contributions of many therapeutic modalities--developmental pediatrics, occupational and physical therapy, hearing and speech, psychology, social services, special education, ophthalamology, neurology, orthopedics and neurosurgery. The poor prognosis for full function within the community is recognized, as are areas of research that require investigation.