From Genetics to Phenotype: Understanding the Diverse Manifestations of Cardiovascular Genetic Diseases in Pediatric Populations

Noonan syndrome revisited

MAP'ing CNS Development and Cognition: An ERKsome Process

Behavior patterns in Duchenne muscular dystrophy: Report on the Parent Project Muscular Dystrophy behavior workshop 8–9 of December 2006, Philadelphia, USA

Objective Congenital conotruncal heart defects were commonly found in DiGeorge (DGS) and velocardiofacial (VCFS) syndromes. The deletion of chromosome 22q 11.2 (del22q) has been demonstrated in sporadic or familial cases of conotruncal heart defect (CTD). The aim of this study was to investigate the frequency of del22q and clinical phenotypic analysis in patients with nonsyndromic CTD at a pediatric thoracic and cardiovascular surgical centre. Methods Seventy-seven non-syndromic CTD children (42 male, 35 female, aged 0-10 years) were recruited. History, physical examination and medical records were reviewed. Venous blood was collected for genomic DNA after informed consent. Chromosome 22q 11.2 microdeletion was screened with Multiplex Ligation-dependent Probe Amplification (MLPA) and Fluorescence in situ hybridization (FISH). Genotype phenotype correlations were performed using Fishers exact test. P values less than 0.05 on a 2-tailed test were considered significant. Results We examined 77 non-syndromic CTD patients for a 22q 11.2 deletion.55 patients presented with tetralogy of fallot (TOF), 4 with pulmonary atresia with ventricular septal defect (PA-VSD), 8 with double outlet right ventricle (DORV) and 10 with transposition of the great arteries (TGA). Six children (7.8%) were found to have a del22q; including four TOF, one DORV and one PA-VSD. Interestingly, none of the ten TGA children had the deletion. Conclusions Chromosome 22q 11.2 microdeletion is detected in 7.9% of children with non-syndromic CTD. There was a tendency of higher 22q11.2 microdeletion prevalence in those with PA-VSD, DORV and TOF. Molecular genetic screening of non-syndromic CTD children may be important for diagnosis and genetic counselling. Key words: Truncus arteriosus,abnormalities; Chromosomes

Congenital Chylothorax as the Initial Presentation of PTPN11-Associated Noonan Syndrome

To establish a normal range for the radiographic distance between cementoenamel junction and alveolar bone crest and the factors affecting distances for the early assessment of periodontal disease in Dravidian pediatric population. Fifty children aged 6 to 8 years were selected based on inclusion and exclusion criteria. Clinical and radiographic examination was performed. All the surfaces were examined starting from the distal surface of primary canine to the mesial surface of first permanent molar. The various risk factors like plaque, calculus, proximal caries, restoration and bleeding on probing were recorded. A pair of bitewing radiographs was taken for each child. Bitewing radiographs were traced and analyzed. It showed that CEJ-ABC distance in primary teeth is about 1 ± 0.5 mm. In the permanent teeth, it was found to be 0.6 ± 0.5 mm in 6 to 8 years age group. CEJ-ABC distance was also affected by different variables like physiologic (eruption and exfoliation) and pathologic factors (plaque, calculus, dental caries, restorations, stainless steel crowns, bleeding on probing and probing depth). CEJ-ABC distances greater than 2.5 mm should be considered under recall and follow-up. Children and adolescents susceptible to periodontal disease should be identified by radiographic means as early as possible in order to prevent the advance of an otherwise possibly destructive disease. The concept of oral health examination and treatment must include examination of the periodontal status of the patient.

Congenital heart disease (CHD) presents a huge medical problem, as it affects between two and eight newborn children per 100 live births.1 Risk factors include alcohol and drug consumption as...

Purpose There is a paucity of data on acquired pericardial diseases in paediatric population, especially from the developing world. The aim of the study was to define the spectrum and profile of pericardial diseases in Indian paediatric population presenting to a tertiary care centre. Methods Children 15 years who presented with pericardial disease (based on clinical and echocardiographic parameters) between January 2010 and December 2016 were recruited. Results A total of 44 patients were enrolled in the study. Their age ranged from 5 months to15 years (mean 6.9±4.8 years), 25 were males. 13 (29.5%) presented with chronic constrictive pericarditis (CCP). The underlying aetiology was tuberculosis in 7 and pyogenic in 3. A total of 24 children had pericardial effusion (PE), cardiac tamponade was present in 4. The aetiology of PE was pyogenic in 11, tubercular in 6 and malignancy in 4. Effusive constrictive pericarditis was seen in 5. Overall tuberculosis was the aetiology in 18 (40.9%) patients. Pericardiocentesis was performed in 27 children, of these 23 had pigtail catheter insertion for drainage. Despite treatment, 60% of patients with tubercular and 45% of patients with purulent PE developed CCP. 18 patients underwent pericardiectomy. Two patients died, one with purulent PE, he died of uncontrolled sepsis and multi-organ failure. The second patient died of low cardiac output following pericardiectomy. Conclusion In our country tuberculosis still remains as the most common cause of acquired pericardial disease, followed by purulent pericarditis. Many cases progress to constrictive physiology despite treatment, requiring pericardiectomy.

To describe fatigue in Duchenne muscular dystrophy (DMD) from patients' and parents' perspectives and to explore risk factors for fatigue in children and adolescents with DMD. A multicentre, cross-sectional study design was used. Seventy-one patients (all males; median age 12y, age range 5-17y) identified via the Canadian Neuromuscular Disease Registry, and their parents completed questionnaires. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale by child self-report and parent proxy-report. Patients with DMD across ages and disease stages experienced greater fatigue compared to typically developing controls from published data. Sleep disturbance symptoms were associated with greater fatigue by child self-report (ρ=-0.42; p=0.003) and parent proxy-report (ρ=-0.51; p<0.001). Depressive symptoms were associated with greater fatigue by child self-report (ρ=-0.46; p<0.001) and parent proxy-report (ρ=-0.45; p<0.001). Lower functional ability was associated with greater fatigue by parent proxy-report (ρ=0.26; p=0.03). Physical activity level, and musculoskeletal, respiratory, and cardiac function were not associated with fatigue. In paediatric DMD, sleep disturbance symptoms and depressive symptoms are potentially modifiable factors associated with fatigue, warranting additional investigation to facilitate the development of therapeutic strategies to reduce fatigue. Fatigue is a major issue in paediatric Duchenne muscular dystrophy (DMD) across ages and disease stages. Sleep disturbance and depressive symptoms are significantly associated with fatigue in paediatric DMD.

Radioulnar Synostosis-Hematology (RUS-H) Syndrome: Description of the New Syndrome and Comparison to Similar Syndromes

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.

Tetralogy of fallot with pulmonary atresia associated with chromosome 22q11 deletion

BackgroundNumerous genetic syndromes associated with heart disease and ocular manifestations have been described. However, a compilation and a summarization of these syndromes for better consultation and comparison have not been performed yet.ObjectiveThe objective of this work is to systematize available evidence in the literature on different syndromes that may cause congenital heart diseases associated with ocular changes, focusing on the types of anatomical and functional changes.MethodA systematic search was performed on Medline electronic databases (PubMed, Embase, Cochrane, Lilacs) of articles published until January 2016. Eligibility criteria were case reports or review articles that evaluated the association of ophthalmic and cardiac abnormalities in genetic syndrome patients younger than 18 years.ResultsThe most frequent genetic syndromes were: Down Syndrome, Velo-cardio-facial / DiGeorge Syndrome, Charge Syndrome and Noonan Syndrome. The most associated cardiac malformations with ocular findings were interatrial communication (77.4%), interventricular communication (51.6%), patent ductus arteriosus (35.4%), pulmonary artery stenosis (25.8%) and tetralogy of Fallot (22.5%).ConclusionDue to their clinical variability, congenital cardiac malformations may progress asymptomatically to heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance.

Objective To explore the clinical diagnosis of tetralogy of Fallot(TOF) children with concurrent DiGeorge syndrome(DGS). Methods Retrospective analyses were conducted for the clinical characteristics of 715 TOF children with concurrent DGS at Henan Provincial People's Hospital and the Third Affiliated Hospital of Zhengzhou University from January of 2008 to October of 2014.Among them, there were 78 definite cases of thymic aplasia(DGS group), including 45 boys and 33 girls with an age range of(9.12±4.35) months and a body mass range of(7.28±2.34) kg.And the remainder was designated as non-DGS group(NDGS group), including 387 boys and 250 girls with an age range of(8.21±5.61) months and a body mass range of(8.19±3.47) kg.In DGS group, genetic screening uncovered 10 cases of chromosome 22q11.2 gene deletion.And based upon this result, DGS group was further divided into genetic and clinical diagnosis subgroups.The genetic diagnosis group had 10 cases, including 6 boys and 4 girls with an age range of(8.12±4.15) months and a body mass range of(6.28±2.74) kg, the clinical diagnosis group had 68 cases, including 39 boys and 29 girls with an age range of(8.19±4.37) months and a body mass range of(7.05±2.39) kg. Results No statistical difference existed in age, body mass or preoperative developmental status of pulmonary vasculature between DGS group and NDGS group(P>0.05). And the preoperative incidence of recurrent pneumonia was obviously higher in DGS group than that in NDGS group(P 0.05). And an inter-group comparison of T lymphocyte immunity defect had no statistical difference(P>0.05). The duration of on-machine and intensive care unit stay was markedly longer in DGS group than that in NDGS group(P 0.05). And an inter-group comparison of T lymphocyte immunity defect had no statistical difference(P>0.05). Conclusions With diverse clinical manifestations, DGS patients may have non-specific findings of cellular immunity defect, hypocalcemia or facial malformation.TOF children with concurrent thymic aplasia should raise an alert so that effective interventions may be adopted to boost their long-term quality of life. Key words: DiGeorge syndrome; Tetralogy of Fallot; Clinical features

A Novel 22q11.2 Microdeletion in DiGeorge Syndrome