Health-related quality of life in preschool children in five health conditions.

OBJECTIVE: To test the responsiveness of the Infant/Toddler Quality of Life Questionnaire (ITQOL) to five health conditions. In addition, to evaluate the impact of the child's age and gender on the ITQOL domain scores. METHODS: Observational study of 494 Dutch preschool-aged children with five clinical conditions and 410 healthy preschool children randomly sampled from the general population. The clinical conditions included neurofibromatosis type 1, wheezing illness, bronchiolitis, functional abdominal complaints, and burns. Health-related quality of life (HRQoL) was assessed by a mailed parent-completed ITQOL. Mean ITQOL scale scores for all conditions were compared with scores obtained from the reference sample. The effect of patient's age and gender on ITQOL scores was assessed using multi-variable regression analysis. RESULTS: In all health conditions, substantially lower scores were found for several ITQOL scales. The conditions had a variable effect on the type of ITQOL domains and a different magnitude of effect. Scores for 'physical functioning', 'bodily pain', and 'general health perceptions' showed the greatest range. Parental impact scales were equally affected by all conditions. In addition to disease type, the child's age and gender had an impact on HRQoL. CONCLUSIONS: The five health conditions (each with a distinct clinical profile) affected the ITQOL scales differently. These results indicate that the ITQOL is sensitive to specific characteristics and symptom expression of the childhood health conditions investigated. This insight into the sensitivity of the ITQOL to health conditions with different symptom expression may help in the interpretation of HRQoL results in future applications.

Functional abdominal complaints in pre-school children: parental reports of health-related quality of life.

PURPOSE: The aim of this study is to assess the influence of functional abdominal complaints (FAC) on health-related quality of life in a group of Dutch pre-school children. METHODS: Parents of children aged up to 6.0 visiting the outpatient pediatric department, Erasmus MC-Sophia, Rotterdam, The Netherlands in the period January 2005-December 2006 for functional abdominal complaints during at least 3 months were asked to complete the Infant/Toddler Quality of life Questionnaire (ITQOL), and questions of the abdominal pain index for use by parents to report pain symptoms in pre-school children. ITQOL scale scores of children with FAC were compared against with Dutch reference values. The abdominal pain index was tested for internal consistency and test-retest reliability. Correlations between ITQOL scale scores and abdominal pain index were assessed by Spearman's rank test. RESULTS: Results are based on 81 questionnaires completed by parents of children with FAC (response rate 61%). Children had a median age of 46 months (interquartile range 27-59), 48% girls. A significant impact was observed on most aspects of quality of life, particularly for physical functioning, general development, bodily pain, temperament and moods, general health perceptions and parental emotional impact. Parents of children with functional constipation tended to report lower scores than those of children with other FAC. The abdominal pain index appeared to be valid and was significantly correlated with ITQOL scales bodily pain and general health perceptions. CONCLUSIONS: A substantial lower health-related quality of life is reported in pre-school children with functional abdominal complaints, with effects on physical, emotional and parental domains. The 5-question severity index of abdominal pain appeared a valid tool and may be helpful to quickly assess the severity of abdominal pain in clinical practice.

Adolescent health-related quality of life following liver and kidney transplantation.

UNLABELLED: Health perceptions of adolescent transplant patients should be considered in providing appropriate healthcare. OBJECTIVES: (i) quantify health-related quality of life (HRQOL) in adolescent liver and kidney transplant patients, (ii) compare caregiver ratings of their children's HRQOL to adolescent self-reports and (iii) examine the relationship between HRQOL and disease-specific disability (DSD). Adolescent liver (n = 51) and kidney (n = 26) transplant recipients and caregivers were surveyed using the CHQ-CF87 and CHQ-PF50. DSD scores were calculated for each patient. The response rate was >70%. Adolescent's psychological and physical health was similar to a healthy population, but general health poorer (p = 0.0006). Caretakers reported lower physical functioning and general health (p = 0.0001) but similar psychological health to a normative population. All caregivers expressed negative emotional impact of their child's health on themselves and family activities (p = 0.0001). Positive correlations were found between liver transplant recipients and caregivers: perceptions of behavior (ICC = 0.55, p < 0.001), mental health (ICC = 0.56, p < 0.001), self-esteem (ICC = 0.68, p

Health-related quality of life of pre-school children with wheezing illness.

Pre-school children are frequently affected by wheezing illness, with substantial influences on their health-related quality of life (HRQL). The Infant/Toddler Quality of Life Questionnaire (ITQOL) is the only generic health status measure for children aged 2 months up to 5 years. In this present study we evaluated the impact of wheezing illness in pre-school children on the HRQL, using the ITQOL. A questionnaire including the ITQOL and ISAAC questions on frequency and severity of respiratory complaints were sent to parents of patients aged 6 months-5 years visiting the outpatient department with wheezing illness. Scale scores of ITQOL of the included children were compared with general population scores. Using multivariate analysis, the influence of general and clinical characteristics on ITQOL scale scores was evaluated. Results are based on 138 children, 59% male, mean age 34 months. Children with wheezing illness scored differently to the general population sample on 8 of the 11 ITQOL scales. Age, comorbidity and employment of the respondent affected scales on child's physical and emotional functioning and parental functioning. Severity of dyspnoea and wheezing, presence of cough, corticosteroid use, and number of GP visits negatively affected scales on the child's physical and emotional functioning. In conclusion, the HRQL as measured by the ITQOL was lower in a group of Dutch pre-school children with wheezing illness compared to a general population sample. The scale scores were sensitive to age, co morbidity, socio-economic situation, and disease severity.

Preliminary evidence on the measurement properties of the Chinese version of the Child Health Questionnaire, parent form (CHQ-pF50) and child form (CHQ-CF87).

UNLABELLED: The objective of this study was to evaluate the reliability and construct validity of the Chinese parent form (PF50) and child form (CF87) of the Child Health Questionnaire (CHQ). METHODS: To assess the construct validity and reliability of the Chinese versions, we invited 1099 parents of healthy children and 816 school children to complete the Chinese CHQ-PF50 and CHQ-CF87, respectively. RESULTS: Psychometric analysis on item convergent validity and discriminant validity showed > or = 99% rates of success for all 10 scales in the CF87 and > or = 94% for all but one scale in the PF50, the exception being general health scale (86%). We observed minimal floor effects for both questionnaires, but substantial ceiling effects for five scales in both the PF50 and CF87 (physical functioning, role-emotional/behavioral, role-physical, bodily pain and family activities). A substantially lower ceiling effect was observed for the physical scale and bodily pain in the CF87 (19% and 25%, respectively) relative to the PF50 (46% and 42%, respectively). The median alpha coefficient for CF87 and PF50 was 0.90 (range, 0.80-0.94) and 0.78 (range, 0.44-0.88), respectively. CONCLUSIONS: Our findings suggest that the Chinese CHQ-PF50 and CHQ-CF87 are robust and sufficiently reliable for group comparisons and perhaps also for use in other Chinese populations.

Reliability and validity of the child health questionnaire-child form (CHQ-CF87) in a Dutch adolescent population.

UNLABELLED: Feasibility, reliability, and discriminative validity of the cross-culturally adapted Dutch version of the originally US child health questionnaire-child form (CHQ-CF87), an 87-item generic pediatric health-related quality of life instrument, were assessed. The success criterion in this first evaluation was the equivalence of psychometric properties of the adapted and the original CHQ. A total of 466 schoolchildren (9-17 years) were invited to complete the questionnaire in the classroom. Test-retest reliability was measured after 14 days in a subgroup (n = 71). Response was 96%. Four scales had ceiling effects (>50%), as was reported in an Australian study. Cronbach alpha-values were adequate (>0.70), except for 'physical functioning' (0.56). Test-retest correlations, not previously reported, were not statistically significant for two CHQ-scales, whereas average retest scores indicated better health for five scales (p < 0.01). The CHQ scales discriminated significantly (p < 0.01) between children without (n = 281) and children with two or more self-reported chronic diseases (n = 59). This is in correspondence with US and Australian reports. CONCLUSIONS: The current data support application of the Dutch CHQ-CF in predominantly healthy populations, e.g. in school settings. Given the limitations of this study and some less favorable results (score distributions, internal consistency, test-retest reliability), further evaluation of the CHQ-CF is recommended, preferably by analyses of item performance and scale validity in international data sets that include varied clinical subgroups.

Cross-cultural adaptation and psychometric evaluation of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ) in 32 countries. Review of the general methodology.

The aim of this project was to cross-culturally adapt and validate the American English version of the Childhood Health Assessment Questionnaire (CHAQ) and of the Child Health Questionnaire (CHQ) in the 32 different member countries of the Paediatric Rheumatology International Trials Organisation (PRINTO). This effort forms part of an international study supported by the European Union to evaluate the health-related quality of life in children with juvenile idiopathic arthritis (JIA) as compared to their healthy peers. A total of 6,644 subjects were enrolled from 32 countries: Argentina, Austria, Belgium, Brazil, Bulgaria, Chile, Croatia, the Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Korea, Latvia, Mexico, the Netherlands, Norway, Poland, Portugal, Russia, Slovakia, Spain, Sweden, Switzerland, Turkey, the United Kingdom, and Yugoslavia. A total of 3,235 patients had JIA (20% systemic onset, 33% polyarticular onset, 17% extended oligoarticular subtype, and 30% persistent oligoarticular subtype) while 3,409 were healthy children. This introductory paper describes the methodology used by all the participants. The results and the translated version of both the CHAQ and the CHQ for each country are fully reported in the following papers. The results of the present study show that cross-cultural adaptation is a valid process to obtain reliable instruments for the different socio-economic and socio-demographic conditions of the countries participating in the project.

The Dutch version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Dutch language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Dutch CHAQ was fully validated with 3 forward and 3 backward translations while the CHQ was already published and therefore it was revalidated. A total of 180 subjects were enrolled: 100 patients with JIA (17% systemic onset, 31% polyarticular onset, 18% extended oligoarticular subtype, and 34% persistent oligoarticular subtype) and 80 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Dutch version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Swedish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Swedish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Swedish CHAQ CHQ were already published and therefore were revalidated in this study. A total of 129 subjects were enrolled: 69 patients with JIA (13% systemic onset, 39% polyarticular onset, 25% extended oligoarticular subtype, and 23% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Swedish version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

The Norwegian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Norwegian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Norwegian CHAQ and CHQ have already been published and therefore they were fully revalidated in this study. A total of 148 subjects were enrolled: 88 patients with JIA (6% systemic onset, 45% polyarticular onset, 10% extended oligoarticular subtype, and 39% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between patients with various JIA subtypes, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to those with persistent oligoarticular arthritis. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Norwegian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Swiss German and Swiss French versions of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Swiss German and Swiss French languages of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Swiss German and Swiss French CHAQ-CHQ were adapted from the German and French versions of the CHAQ-CHQ, and revalidated in this study. A total of 147 subjects were enrolled: 85 patients with JIA (22% systemic onset, 31% polyarticular onset, 32% extended oligoarticular subtype, and 15% persistent oligoarticular subtype) and 62 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Swiss German and Swiss French versions of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

The Austrian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Austrian language of the parentís version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Austrian CHAQ CHQ were adapted from the German version of the CHAQ-CHQ, and revalidated in this study. A total of 134 subjects were enrolled: 74 patients with JIA (9.5% systemic onset, 42% polyarticular onset, 9.5% extended oligoarticular subtype, and 39% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Austrian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The British version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the British language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. A total of 440 subjects were enrolled: 219 patients with JIA (17% systemic onset, 41% polyarticular onset, 33% extended oligoarticular subtype, and 9% persistent oligoarticular subtype) and 221 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the British version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Belgian-Flemish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Belgian-Flemish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Belgian-Flemish CHAQ was fully validated with 3 forward and 3 backward translations, while the Belgian-Flemish CHQ was equal to the Dutch version and revalidated in this study. The French version of both CHAQ and CHQ was exactly the same as the one used in France. A total of 199 subjects were enrolled: 53 patients with JIA (11% systemic onset, 40% polyarticular onset, 13% extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and 146 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular onset, and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Belgian-Flemish version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The German version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the German language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The German CHAQ was fully validated with 3 forward and 3 backward translations, while the CHQ has already been published and therefore it was revalidated. A total of 197 subjects were enrolled: 142 patients with JIA (5% systemic onset, 13% polyarticular onset, 8% extended oligoarticular subtype, and 74% persistent oligoarticular subtype) and 55 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the German versions of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

The health impact of chronic recurrent rhinosinusitis in children.

OBJECTIVES: To report and quantify the health-related quality of life of children who require surgical intervention for chronic recurrent rhinosinusitis and to assess the perspective of the child vs that of the parent. DESIGN: Prospective, observational. PATIENTS AND INTERVENTION: Twenty-one of a consecutive sample of 35 children undergoing endoscopic sinus surgery for infectious indications completed, along with their parents, the Child Health Questionnaire. The Child Health Questionnaire measures in parallel both child and parent perceptions of health by means of separate parent proxy report (Child Health Questionnaire-Parent Form 50) and child self-report (Child Health Questionnaire-Child Form 87) questionnaires concerning physical and psychosocial functioning. MAIN OUTCOME MEASURES: Tabulated scores from both the Child Health Questionnaire-Parent Form 50 and Child Health Questionnaire-Child Form 87 were compared with published data from age-matched normative populations and several pediatric chronic disease groups. RESULTS: Significant decrements in the general health of children with chronic recurrent rhinosinusitis compared with a normative sample were observed for both child- and parent-reported data, particularly in the physical domains. Children with rhinosinusitis were perceived by their parents to have significantly more bodily pain (P<.001)and to be more limited in their physical activities (P<.05)than children with asthma, juvenile rheumatoid arthritis, and other chronic disorders. Parent-child perceptions did vary, with parents reporting more pain and general behavioral effects relative to their children's reports in these areas. CONCLUSION: The health impact of chronic recurrent rhinosinusitis as reported by the subjective evaluations of pediatric patients and their parents is severe.

Use of the child health questionnaire in a sample of moderate and low-income inner-city children with asthma.

The Child Health Questionnaire (CHQ-PF50) is one of several recent efforts to gauge pediatric, health-related quality of life from the patient's (or parent's) perspective. Although tested extensively with healthy children, more information is needed about CHQ performance among children with chronic conditions such as asthma. The current study extends previous work by examining the CHQ's psychometric performance in a sample of children with asthma, overrepresenting those at high risk for poor outcomes. Seventy-four adult caregivers of children with asthma completed the CHQ. Internal consistency reliability was consistently high for all but one scale. Intraclass correlation coefficients ranged from a low of 0.37 to a high of 0.84. Tests of validity found CHQ scales better at distinguishing levels of disease severity as defined by symptom activity than medication use or pulmonary function tests. Performance of the CHQ-PF50 in a sample of low-income to moderate income inner-city parents of children with asthma presented mixed results. The instrument addresses a broad range of concepts but some scales may be more salient than others in assessing health status of children at highest risk for asthma morbidity. Future efforts must compare condition-specific and generic instruments to evaluate their relative strengths and weakness, as well as potential links between them.

Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioral disorders that most often arise from a 4-Mb deletion of chromosome 15q11-q13 during paternal or maternal gametogenesis, respectively. At a de novo frequency of approximately.67-1/10,000 births, these deletions represent a common structural chromosome change in the human genome. To elucidate the mechanism underlying these events, we characterized the regions that contain two proximal breakpoint clusters and a distal cluster. Novel DNA sequences potentially associated with the breakpoints were positionally cloned from YACs within or near these regions. Analyses of rodent-human somatic-cell hybrids, YAC contigs, and FISH of normal or rearranged chromosomes 15 identified duplicated sequences (the END repeats) at or near the breakpoints. The END-repeat units are derived from large genomic duplications of a novel gene (HERC2), many copies of which are transcriptionally active in germline tissues. One of five PWS/AS patients analyzed to date has an identifiable, rearranged HERC2 transcript derived from the deletion event. We postulate that the END repeats flanking 15q11-q13 mediate homologous recombination resulting in deletion. Furthermore, we propose that active transcription of these repeats in male and female germ cells may facilitate the homologous recombination process.