Feasibility and performance of home sleep apnea testing in youth with Down syndrome.

STUDY OBJECTIVES: In-laboratory polysomnography is recommended for the evaluation of obstructive sleep apnea (OSA) in youth with Down syndrome. However, insufficient sleep laboratories are available, particularly for youth with neurocognitive disabilities such as Down syndrome. We hypothesized that level II home sleep apnea testing (HSAT) would be feasible, acceptable, and accurate in detecting polysomnography-defined moderate-severe OSA in youth with Down syndrome. METHODS: Youth 6 to 25 years old with Down syndrome were recruited to undergo in-home level II HSAT with electroencephalogram and in-lab polysomnography. Parents completed questionnaires assessing feasibility, acceptability, and test preference. HSAT, scored blinded to polysomnography result, were compared to reference polysomnography. RESULTS: Forty-three youth (23 female) aged [median (range)] 15.5 (6.1, 25.1) years participated in the study. Forty-one participants were able to complete HSAT and 41 completed polysomnography, with 40 who underwent both tests. HSAT was preferred to polysomnography by 73.7% of parents. Total sleep time for HSAT was 437 ± 123 minutes vs 366 ± 90 minutes for polysomnography (P = .003). Obstructive apnea-hypopnea index by polysomnography was 12.7 events/h (0.2, 113.8), and 32 youth (80%) who completed all testing had OSA. Compared to polysomnography, sensitivity of HSAT was: 0.81, specificity was 0.75, accuracy was 0.8 including 2 youth whose HSAT demonstrated OSA when polysomnography did not. CONCLUSIONS: In youth with Down syndrome, level II HSAT was well-tolerated, preferred compared to in-lab polysomnography, and had good accuracy for detecting moderate-severe OSA. Level II HSAT could provide a means for expanding the evaluation of OSA in youth with Down syndrome. CITATION: Cielo CM, Kelly A, Xanthopoulos M, et al. Feasibility and performance of home sleep apnea testing in youth with Down syndrome J Clin Sleep Med. 2023;19(9):1605-1613.

Physical Activity in Youth with Down Syndrome and Its Relationship with Adiposity.

PURPOSE: The aims of this study are to (1) compare physical activity (PA) and sedentary activity (SA) in youth with and without Down syndrome (DS and non-DS) and examine the relationships of PA and SA with their traditional risk factors (age, sex, race, and body mass index Z score [BMI-Z]) and (2) explore the relationship of PA with visceral fat (VFAT) in both groups. METHODS: SenseWear accelerometry data from at least 2 weekdays and 1 weekend day were collected from youth with DS (N = 77) and non-DS (N = 57) youth. VFAT was measured by dual x-ray absorptiometry. RESULTS: In age-, sex-, race-, and BMI-Z-adjusted models, those with DS engaged in more minutes of light PA (LPA) ( p < 0.0001) and less SA ( p = 0.003) and trended toward fewer minutes of moderate-to-vigorous PA (MVPA) ( p = 0.08) than non-DS youth. No race or sex differences in MVPA were detected in those with DS, unlike non-DS. After additional adjustment for pubertal status, the relationship between MVPA and VFAT approached significance ( p = 0.06), whereas the relationships of LPA and SA with VFAT were maintained ( p ≤ 0.0001 for both). CONCLUSION: Youth with DS engage in more LPA compared with non-DS, which, in typically developing populations, can confer a more favorable weight status. Increasing the opportunity for youth with DS to engage in LPA as part of their activities of daily living may offer a viable strategy for achieving healthy weight when barriers restrict pursuit of more vigorous PA.

Diet Quality and Cardiometabolic Risk Factors in Adolescents with Down Syndrome.

BACKGROUND: Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth. OBJECTIVE: The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls. DESIGN: Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children's hospitals (Children's Hospital of Philadelphia and the Children's National Health System in Washington, DC). PARTICIPANTS AND SETTING: CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses. MAIN OUTCOME MEASURES: The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected. STATISTICAL ANALYSES PERFORMED: Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score. RESULTS: Compared with controls (n = 100, median age = 14.8 years [interquartile range = 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n = 143, median age = 14.7 years [interquartile range = 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range = 46.8 to 58.6] vs controls: 45.1 [interquartile range = 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (-0.14, 95% CI -0.29 to 0.00; P = 0.053). CONCLUSIONS: Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.

Neurologic and developmental considerations in children with medical complexity.

Children with medical complexity are at increased risk of neurodevelopmental conditions. Signs or symptoms of neurodevelopmental conditions may be more apparent in the context of a medical illness or hospitalization. Thus, primary care, front-line subspecialty and hospital-based pediatricians are encouraged to be on the alert for these conditions from infancy through adolescence. Medical and mental health issues must be considered in the differential diagnoses when children with neurodevelopmental conditions present with a change or regression in their behavior. Management of maladaptive behaviors includes managing the underlying medical and mental health conditions that are contributing to the behavior, environmental supports, behavior therapy interventions, communication and other skills building support for the child, as well as judicious use of medication when necessary.

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome.

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10-20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross-sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.

Cardiometabolic Risk and Body Composition in Youth With Down Syndrome.

BACKGROUND AND OBJECTIVES: Whether BMI captures adiposity and cardiometabolic risk in Down syndrome (DS), a condition associated with obesity, short stature, and altered body proportions, is not known. We compared cardiometabolic risk measures in youth with DS and typically developing matched controls. METHODS: Youth with (n = 150) and without (n = 103) DS of comparable age (10-20 years), sex, race, ethnicity, and BMI percentile underwent whole-body dual-energy X-ray absorptiometry, fasting glucose, insulin, lipids, lipoprotein particles, inflammatory factors, and when BMI percentile ≥85, an oral glucose tolerance test. RESULTS: Sixty-four percent of youth with DS had BMI percentile ≥85. Among these, no difference in glucose, insulin, or insulin resistance was detected, but prediabetes was more prevalent with DS (26.4% vs 10.3%; P = .025) after adjustment for demographics, pubertal status, and BMI z score (odds ratio = 3.2; P = .026). Among all participants, those with DS had higher low-density lipoprotein cholesterol (median 107 [interquartile range 89-128] vs 88.5 [79-103] mg/dL; P < .00005), triglycerides (89.5 [73-133] vs 71.5 [56-104] mg/dL; P < .00005), non-high-density lipoprotein cholesterol (non-HDL-C; 128 [104-153] vs 107 [92-123] mg/dL; P < .00005), and triglycerides/HDL-C (2.2 [1.6-3.4] vs 1.7 [1.1-2.5] mg/dL; P = .0003) and lower levels of HDL-C (41 [36.5-47] vs 45 [37-53] mg/dL; P = .012). DS youth had higher high-sensitivity C-reactive protein, interleukin-6, small low-density lipoprotein particles (LDL-P), and total LDL-P, but similar LDL-P size. Youth with DS had less visceral fat (VFAT), fat mass, and lean mass for BMI z score, but greater VFAT at higher fat mass. However, VFAT did not fully explain the increased prevalence of dyslipidemia or prediabetes in youth with DS. CONCLUSIONS: Despite similar insulin resistance, youth with DS had greater prevalence of dyslipidemia and prediabetes than typically developing youth, which was not fully explained by VFAT.

Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome.

OBJECTIVES: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome. STUDY DESIGN: Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV. RESULTS: Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R2 = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R2 = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001). CONCLUSIONS: The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01821300.

Clinical and molecular spectrum of CHOPS syndrome.

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.

Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome.

Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height2.7 as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10-20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E'); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min-max]): DS had lower height (cm) (144.5 [116.7-170.3] vs. 163.3 [134.8-186.7]; p < 0.0001); LBM (kg) (33.48 [14.5-62.3] vs 41.8 [18.07-72.46], p < 0.0001); and LVM (g) (68.3 [32.1-135] vs 94.0 [43.9-164.6], p < 0.0001); similar EF (%) (65 [54-77] vs 64 [53-77], p = 0.59); and higher E/E' (8.41 [5.54-21.4] vs 5.81 [3.44-9.56], p < 0.0001). In height2.7-adjusted models, LVM was lower in DS (ß = - 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (ß = - 15.1, p < 0.0001), a finding not explained by MVPA. E/E' remained higher in DS after adjustment for age, height, HR, SBP, and BMI (ß = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height2.7, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.Clinical Trial Registration: NCT01821300.

Caregiver-Reported Quality of Life in Youth with Down Syndrome.

OBJECTIVES: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN: Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index ≥95th percentile for age and sex. RESULTS: Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. CONCLUSION: Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. CLINICAL TRIAL REGISTRATION: NCT01821300.

Body composition estimation using skinfolds in children with and without health conditions affecting growth and body composition.

BACKGROUND: Body composition prediction equations using skinfolds are useful alternatives to advanced techniques, but their utility across diverse paediatric populations is unknown. AIM: To evaluate published and new prediction equations across diverse samples of children with health conditions affecting growth and body composition. SUBJECTS AND METHODS: Anthropometric and dual-energy X-ray absorptiometry (DXA) body composition measures were obtained in children with Down syndrome (n = 59), Crohn disease (n = 128), steroid-sensitive nephrotic syndrome (n = 67) and a healthy reference group (n = 835). Published body composition equations were evaluated. New equations were developed for ages 3-21 years using the healthy reference sample and validated in other groups and national survey data. RESULTS: Fat mass (FM), fat-free mass (FFM) and percentage body fat (%BF) from published equations were highly correlated with DXA-derived measures (r = 0.71-0.98), but with poor agreement (mean difference = 2.4 kg, -1.9 kg and 6.3% for FM, FFM and %BF). New equations produced similar correlations (r = 0.85-1.0) with improved agreement for the reference group (0.2 kg, 0.4 kg and 0.0% for FM, FFM and %BF, respectively) and in sub-groups. CONCLUSIONS: New body composition prediction equations show excellent agreement with DXA and improve body composition estimation in healthy children and those with selected conditions affecting growth.

Body Composition and BMI Growth Charts in Children With Down Syndrome.

BACKGROUND AND OBJECTIVES: New US Down syndrome (DS) BMI growth charts were recently published, but their utility in identifying children with excess adiposity or increased cardiometabolic risk (CMR) remains unknown. We sought to compare the ability of the Centers for Disease Control and Prevention (CDC) BMI 85th percentile and DS-specific BMI 85th percentile to identify excess adiposity in children with DS. METHODS: Participants with DS aged 10 to 20 years were enrolled in a cross-sectional CMR study. Data from typically developing children enrolled in the Bone Mineral Density in Childhood Study (BMDCS) were used for comparison. Sensitivity and specificity were calculated to assess the CDC BMI 85th percentile in the BMDCS and DS groups, and the DS-specific BMI 85th percentile in the DS group, relative to fat mass index (FMI) ≥80th percentile, a threshold associated with increased CMR. RESULTS: Included were 121 DS participants (age 14.8 ± 3.3 years, 57% girls) and 7978 BMDCS reference data points (age 15.0 ± 3.0 years, 51.3% girls). The CDC BMI 85th percentile identified FMI ≥80th percentile with 96.9% sensitivity and 87.4% specificity in typically developing children. Similarly, the CDC BMI 85th percentile identified FMI ≥80th percentile with 100% sensitivity and 78.3% specificity in children with DS. In contrast, the sensitivity of the DS-specific BMI 85th percentile was only 62.3% (P < .0001), but was 100% specific. CONCLUSIONS: For children with DS ≥10 years, the CDC BMI growth chart 85th percentile is a better indicator of excess adiposity, than the new DS-specific BMI charts. Additional studies are needed to clarify the relationships of BMI and FMI with CMR in DS.

Benefits and limitations of a multidisciplinary approach to individualized management of Cornelia de Lange syndrome and related diagnoses.

Given the clinical complexities of Cornelia de Lange Syndrome (CdLS), the Center for CdLS and Related Diagnoses at The Children's Hospital of Philadelphia (CHOP) and The Multidisciplinary Clinic for Adolescents and Adults at Greater Baltimore Medical Center (GBMC) were established to develop a comprehensive approach to clinical management and research issues relevant to CdLS. Little work has been done to evaluate the general utility of a multispecialty approach to patient care. Previous research demonstrates several advantages and disadvantages of multispecialty care. This research aims to better understand the benefits and limitations of a multidisciplinary clinic setting for individuals with CdLS and related diagnoses. Parents of children with CdLS and related diagnoses who have visited a multidisciplinary clinic (N = 52) and who have not visited a multidisciplinary clinic (N = 69) were surveyed to investigate their attitudes. About 90.0% of multispecialty clinic attendees indicated a preference for multidisciplinary care. However, some respondents cited a need for additional clinic services including more opportunity to meet with other specialists (N = 20), such as behavioral health, and increased information about research studies (N = 15). Travel distance and expenses often prevented families' multidisciplinary clinic attendance (N = 41 and N = 35, respectively). Despite identified limitations, these findings contribute to the evidence demonstrating the utility of a multispecialty approach to patient care. This approach ultimately has the potential to not just improve healthcare for individuals with CdLS but for those with medically complex diagnoses in general. © 2016 Wiley Periodicals, Inc.

Relationship between obstructive sleep apnea cardiac complications and sleepiness in children with Down syndrome.

OBJECTIVE/BACKGROUND: Children with Down syndrome (DS) have a high rate of pulmonary hypertension and sleepiness. They also have a high prevalence of obstructive sleep apnea syndrome (OSAS). We hypothesized that OSAS was associated with cardiovascular dysfunction and sleepiness in children with DS, and that this dysfunction was partly reversible. PATIENTS/METHODS: A total of 23 children with DS, aged 8-19 years, were evaluated with polysomnography, echocardiography, and measurement of brain natriuretic peptide (BNP). Children having OSAS were randomized to four months of actual or sham continuous positive airway pressure (CPAP) in a double-blinded fashion. RESULTS: Of the total participants, 20 (87%) had OSAS. On echocardiography, no participant was found to have pulmonary hypertension, and all participants had a BNP <10 pg/mL. The early/tissue Doppler (E/e') of the lateral mitral annulus, a measure of worse left ventricular (LV) diastolic function, correlated with the arousal index (r = 0.42, p = 0.043) and apnea hypopnea index (AHI; r = 0.61, p = 0.002) and inversely with the SpO2 nadir (r = -0.61, p = 0.002). Participants with OSAS had a high pediatric Epworth score [median interquartile range (IQR) = 8(4,9)],correlating with the arousal index (r = 0.49, p = 0.016). At four months, there were no changes in cardiovascular outcomes or sleepiness between those on actual versus sham CPAP. Hours of actual CPAP use was associated with improved E/e' mitral lateral (r = -0.48, p = 0.044), but surprisingly also correlated with LV mass z-score (r = 0.54, p = 0.018). CONCLUSIONS: In children with DS, LV diastolic function correlated with OSAS severity, with improvement with CPAP use. There was a tendency towards increased sleepiness in those with OSAS, which correlated with the arousal index. Larger studies are warranted to confirm these findings.

Growth Charts for Children With Down Syndrome in the United States.

BACKGROUND AND OBJECTIVES: Children with Down syndrome (DS) have lower birth weights and grow more slowly than children without DS. Advances in and increased access to medical care have improved the health and well-being of individuals with DS; however, it is unknown whether their growth has also improved. Our objective was to develop new growth charts for children with DS and compare them to older charts from the United States and more contemporary charts from the United Kingdom. METHODS: The Down Syndrome Growing Up Study (DSGS) enrolled a convenience sample of children with DS up to 20 years of age and followed them longitudinally. Growth parameters were measured by research anthropometrists. Sex-specific growth charts were generated for the age ranges birth to 36 months and 2 to 20 years using the LMS method. Weight-for-length and BMI charts were also generated. Comparisons with other curves were presented graphically. RESULTS: New DSGS growth charts were developed by using 1520 measurements on 637 participants. DSGS growth charts for children <36 months of age showed marked improvements in weight compared with older US charts. DSGS charts for 2- to 20-year-olds showed that contemporary males are taller than previous charts showed. Generally, the DSGS growth charts are similar to the UK charts. CONCLUSIONS: The DSGS growth charts can be used as screening tools to assess growth and nutritional status and to provide indications of how growth of an individual child compares with peers of the same age and sex with DS.

Cornelia de Lange syndrome: further delineation of phenotype, cohesin biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts.

Cornelia de Lange syndrome (CdLS) is the prototype for the cohesinopathy disorders that have mutations in genes associated with the cohesin subunit in all cells. Roberts syndrome is the next most common cohesinopathy. In addition to the developmental implications of cohesin biology, there is much translational and basic research, with progress towards potential treatment for these conditions. Clinically, there are many issues in CdLS faced by the individual, parents and caretakers, professionals, and schools. The following abstracts are presentations from the 5th Cornelia de Lange Syndrome Scientific and Educational Symposium on June 20-21, 2012, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting, Lincolnshire, IL. The research committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts and subsequently disseminates the information to the families. In addition to the basic science and clinical discussions, there were educationally-focused talks related to practical aspects of management at home and in school. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.

Clinical practice guideline: tympanostomy tubes in children--executive summary.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Tympanostomy Tubes in Children. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 12 recommendations developed address patient selection, surgical indications for and management of tympanostomy tubes in children. The development group broadly discussed indications for tube placement, perioperative management, care of children with indwelling tubes, and outcomes of tympanostomy tube surgery. Given the lack of current published guidance on surgical indications, the group focused on situations in which tube insertion would be optional, recommended, or not recommended. Additional emphasis was placed on opportunities for quality improvement, particularly regarding shared decision making and care of children with existing tubes.

Clinical practice guideline: Tympanostomy tubes in children.

OBJECTIVE: Insertion of tympanostomy tubes is the most common ambulatory surgery performed on children in the United States. Tympanostomy tubes are most often inserted because of persistent middle ear fluid, frequent ear infections, or ear infections that persist after antibiotic therapy. Despite the frequency of tympanostomy tube insertion, there are currently no clinical practice guidelines in the United States that address specific indications for surgery. This guideline is intended for any clinician involved in managing children, aged 6 months to 12 years, with tympanostomy tubes or being considered for tympanostomy tubes in any care setting, as an intervention for otitis media of any type. PURPOSE: The primary purpose of this clinical practice guideline is to provide clinicians with evidence-based recommendations on patient selection and surgical indications for and management of tympanostomy tubes in children. The development group broadly discussed indications for tube placement, perioperative management, care of children with indwelling tubes, and outcomes of tympanostomy tube surgery. Given the lack of current published guidance on surgical indications, the group focused on situations in which tube insertion would be optional, recommended, or not recommended. Additional emphasis was placed on opportunities for quality improvement, particularly regarding shared decision making and care of children with existing tubes. ACTION STATEMENTS: The development group made a strong recommendation that clinicians should prescribe topical antibiotic eardrops only, without oral antibiotics, for children with uncomplicated acute tympanostomy tube otorrhea. The panel made recommendations that (1) clinicians should not perform tympanostomy tube insertion in children with a single episode of otitis media with effusion (OME) of less than 3 months' duration; (2) clinicians should obtain an age-appropriate hearing test if OME persists for 3 months or longer (chronic OME) or prior to surgery when a child becomes a candidate for tympanostomy tube insertion; (3) clinicians should offer bilateral tympanostomy tube insertion to children with bilateral OME for 3 months or longer (chronic OME) and documented hearing difficulties; (4) clinicians should reevaluate, at 3- to 6-month intervals, children with chronic OME who did not receive tympanostomy tubes until the effusion is no longer present, significant hearing loss is detected, or structural abnormalities of the tympanic membrane or middle ear are suspected; (5) clinicians should not perform tympanostomy tube insertion in children with recurrent acute otitis media (AOM) who do not have middle ear effusion in either ear at the time of assessment for tube candidacy; (6) clinicians should offer bilateral tympanostomy tube insertion to children with recurrent AOM who have unilateral or bilateral middle ear effusion at the time of assessment for tube candidacy; (7) clinicians should determine if a child with recurrent AOM or with OME of any duration is at increased risk for speech, language, or learning problems from otitis media because of baseline sensory, physical, cognitive, or behavioral factors; (8) in the perioperative period, clinicians should educate caregivers of children with tympanostomy tubes regarding the expected duration of tube function, recommended follow-up schedule, and detection of complications; (9) clinicians should not encourage routine, prophylactic water precautions (use of earplugs, headbands; avoidance of swimming or water sports) for children with tympanostomy tubes. The development group provided the following options: (1) clinicians may perform tympanostomy tube insertion in children with unilateral or bilateral OME for 3 months or longer (chronic OME) and symptoms that are likely attributable to OME including, but not limited to, vestibular problems, poor school performance, behavioral problems, ear discomfort, or reduced quality of life and (2) clinicians may perform tympanostomy tube insertion in at-risk children with unilateral or bilateral OME that is unlikely to resolve quickly as reflected by a type B (flat) tympanogram or persistence of effusion for 3 months or longer (chronic OME).

Developmental and behavioral characteristics of individuals with Pallister-Killian syndrome.

Pallister-Killian syndrome is a sporadic disorder caused by the presence of mosaic tetrasomy of the short arms of chromosome 12. Case reports of children with Pallister-Killian syndrome have described a range of developmental and behavioral outcomes, but no systematic studies of these outcomes exist. The objective of this study was to describe developmental and behavioral characteristics of individuals with Pallister-Killian syndrome participating in a national meeting of families and their affected children. Sixteen individuals with Pallister-Killian syndrome, ages 16 months to 19 years, were studied using questionnaires and direct interview. Among the 16 patients enrolled in the study, 3 probands were between 16 and 19 months, and had severe developmental delay. Among the rest of the 13 probands older than 24 months, 11 children had a developmental level of less than 8 months age equivalent. They were non-ambulatory, non-verbal, and passive, requiring extensive assistance in daily living. There were two higher functioning children who were ambulatory, and verbal. One of these children met criteria for Autism on the Autism Diagnostic Interview-Revised. Thus, although most individuals with Pallister-Killian syndrome studied showed profound intellectual disability and sensory impairments, individuals with Pallister-Killian syndrome can have mild to moderate intellectual disability. Therefore, in individuals with physical examination findings of Pallister-Killian syndrome, formal diagnostic testing should be considered, even in individuals with mild to moderate intellectual disability. Further studies will be needed to determine if these higher functioning children with Pallister-Killian syndrome are at increased risk for autism.

Novel clinical manifestations in Pallister-Killian syndrome: comprehensive evaluation of 59 affected individuals and review of previously reported cases.

Pallister-Killian syndrome is a rare, multi-system developmental diagnosis typically caused by tetrasomy of chromosome 12p that exhibits tissue-limited mosaicism. The spectrum of clinical manifestations in Pallister-Killian syndrome is wide and includes craniofacial anomalies, clefts, ophthalmologic, audiologic, cardiac, musculoskeletal, diaphragmatic, gastrointestinal, genitourinary, and cutaneous anomalies in association with intellectual disability and seizures. Growth parameters are often normal to elevated at birth with deceleration of growth postnatally. No formal estimate of the prevalence of Pallister-Killian syndrome has been made. Here, we report the clinical findings in 59 individuals with Pallister-Killian syndrome who were ascertained at Pallister-Killian syndrome Foundation family meetings held in the summers of 2006, 2008, 2009, and 2010. In addition, the clinical findings of 152 cases reported in the medical literature were reviewed and compared to the cohort examined here. Several novel clinical characteristics were identified through detailed dysmorphology examinations of this cohort and reassertion of a mild developmental variant is described. This report expands the clinical manifestations of Pallister-Killian syndrome and highlights the variable expressivity of this diagnosis with important implications for diagnosis and counseling.