Genotype-phenotype correlation in Prader-Willi syndrome: A large-sample analysis in China.

The genotype-phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endocrine abnormalities, growth and development abnormalities, and other clinical phenotypes. The relationships between genotypes and phenotypes in the major categories of PWS were analyzed. A total of 586 PWS cases with confirmed molecular diagnosis and genotyping were included in this study. Among them, 83.8% belonged to the deletion type, 10.9% the uniparental disomy (UPD) type, and 5.3% the imprinting defect (ID) type. Age-wide comparison among the three groups: The rate of hypopigmentation in the deletion group was higher than that in the UPD group (88.8% vs. 60.9%; p < 0.05); A total of 62 patients (14.2%) had epilepsy; and no statistical significance was found among the three groups (p = 0.110). Age-wide comparison between the deletion and non-deletion types: the rate of skin hypopigmentation and epilepsy in the deletion group was significantly higher than that in the non-deletion group (88.8% vs. 68.4%, p < 0.001; 15.9% vs. 7.6%, p = 0.040). The intergroup comparison for the >2-year age group: there were significant intergroup differences in the language development delay among the three groups (p < 0.001). The incidence of delayed language development was the highest in the deletion group, followed by the UPD group, and the lowest in the ID group. The rates of obesity and hyperphagia in the deletion group were also higher than those in the non-deletion group (71.1% vs. 58.9%, p = 0.041; 75.7% vs. 62.0%, p = 0.016). There are significant differences in the rates of skin hypopigmentation and language developmental delay among the deletion, UPD, and ID genotypes. The patients with deletion type had significantly higher rates of lighter skin color, obesity, hyperphagia, language developmental delay, and epilepsy. The results of this study will help clinicians better understand the impact of different PWS molecular etiologies on specific phenotypes.

Do Parents of Children with ADHD Know the Disease? Results from a Cross-Sectional Survey in Zhejiang, China.

Parents' knowledge, attitudes, and beliefs about attention-deficit/hyperactivity disorder (ADHD) are crucial in the selection of the treatment strategy and how to care for children with ADHD. However, little is known about parents' conception in mainland China. A semi-structured questionnaire was used to assess this information with 25 true/false questions regarding ADHD, and other questions investigating the methods of acquiring ADHD-related information, treatment preference, and concerns about ADHD treatment strategy. We found that the average score of all the participants was 17.42 ± 2.69 (total of 25 points) for the questionnaire on knowledge, attitudes, and beliefs about ADHD. This indicated that the parents had insufficient knowledge of this disease profile. They always accessed specialized information through mobile internet. For the treatment options, the investigated parents chose psychotherapy treatment rather than medications, in that they worried about the side effects of medication and expected to find alternative treatment strategies. The present investigation demonstrated that most parents lack knowledge about ADHD in treatment decision making in China. Medical professionals should provide parents with evidence-based ADHD-related information to help them understand this disease.

Knowledge and beliefs about autism spectrum disorders among physicians: a cross-sectional survey from China.

BACKGROUND: The incidence of autism spectrum disorders (ASDs) is increasing greatly, with high demands for earlier diagnosis and intervention. However, little is known about ASD knowledge and beliefs among physicians in China. METHODS: A questionnaire survey was used to assess the knowledge and beliefs about the diagnosis and management of ASD and 24 beliefs regarding the treatment and prognostic aspects of ASD among physicians of any medical specialty in China. RESULTS: A total of 1160 physicians were recruited and surveyed, with an average score of 8.48±2.66 (total of 18 points) for the questionnaire on the main symptoms of ASD and 14.35±3.69 (total of 24 points) for beliefs about ASD. Physicians' age, sex, specialty and practice years were related to their knowledge of identifying patients with ASD. Physicians specialising in paediatrics/psychology/psychiatry scored higher than those specialising in other specialties both in response to diagnostic questions (8.98±2.63 vs 8.30±2.65, p<0.001) and beliefs about ASD (15.57±3.44 vs 13.97±3.97, p<0.001). CONCLUSIONS: Knowledge and beliefs about ASD symptoms, diagnosis and treatment are insufficient among physicians in China. Education and training programmes on this topic should be enhanced in physicians of all specialties, especially for male physicians who have short years in practice.

Genotype-Phenotype Correlations in Angelman Syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disease that is caused by the loss of function of the maternal copy of ubiquitin-protein ligase E3A (UBE3A) on the chromosome 15q11-13 region. AS is characterized by global developmental delay, severe intellectual disability, lack of speech, happy disposition, ataxia, epilepsy, and distinct behavioral profile. There are four molecular mechanisms of etiology: maternal deletion of chromosome 15q11-q13, paternal uniparental disomy of chromosome 15q11-q13, imprinting defects, and maternally inherited UBE3A mutations. Different genetic types may show different phenotypes in performance, seizure, behavior, sleep, and other aspects. AS caused by maternal deletion of 15q11-13 appears to have worse development, cognitive skills, albinism, ataxia, and more autistic features than those of other genotypes. Children with a UBE3A mutation have less severe phenotypes and a nearly normal development quotient. In this review, we proposed to review genotype-phenotype correlations based on different genotypes. Understanding the pathophysiology of the different genotypes and the genotype-phenotype correlations will offer an opportunity for individualized treatment and genetic counseling. Genotype-phenotype correlations based on larger data should be carried out for identifying new treatment modalities.

Ketoacidotic crisis after vaccination in a girl with beta-ketothiolase deficiency: a case report.

Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) is a rare autosomal recessive disease caused by ACAT1 gene pathogenic variant involving isoleucine catabolism and ketone body metabolism disorder. The onset of ketoacidotic crisis commonly follows prior concurrent diseases or triggers including long-time fasting, infections, intake of high-level of lipids or proteins, etc. A girl aged 8 months presented with fever and cough on the day after vaccination of the second dose of Japanese encephalitis inactivated; on the second day after vaccination, she was admitted to the local hospital because of unconsciousness and dyspnea. After 1 day of treatment at the local hospital, she was referred to our hospital due to exacerbated conditions including unconsciousness and convulsion. When referring to our hospital, she had metabolic acidosis, hypokalemia, hypernatremia, hyperammonemia, and a Glasgow coma scale of 8 and Kussmaul breathing. Five percent NaHCO3 (24 mL/kg), glucose and insulin (4-6 g glucose/1 U insulin) were continuously infused for correcting acidosis. L-carnitine (350 mg/kg/day) was given for ensuring the energy and increasing exudates of metabolites after admission. Protein was limited at 1.5 g/kg/day. Mechanical ventilation support and hemodialysis were used. The patient was still under unconsciousness after 2 weeks of intensive treatment in the Pediatric Intensive Care Unit (PICU). Due to her severe illness, the child's parents ultimately decided to redirect their goals of care, and the child was discharged home where she died. For children with acute unexplainable metabolic acidosis, differential diagnosis of T2 deficiency should be considered. Rigorous indicative treatments including mechanical ventilation and hemodialysis should be given timely if ketoacidotic crisis occurred in patients with T2 deficiency.

Perinatal features of Prader-Willi syndrome: a Chinese cohort of 134 patients.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by lacking expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features of 134 Chinese individuals with PWS. METHODS: This study included the patients of a PWS registry in China. Anonymous data of 134 patients were abstracted. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA. RESULTS: This study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal uniparental disomy). Higher mean maternal age was found in this cohort (30.5 vs. 26.7), particularly in the maternal uniparental disomy (UPD) group (36.0 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5 and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, 94.8% of whom had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization, however, 97.8% of them discontinued tube feeding after discharge. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (both P < 0.05). CONCLUSIONS: Differential diagnosis of PWS should be highlighted if infants having following perinatal factors including polyhydramnios, decreased intrauterine fetal movements, caesarean section, low birth weight, feeding difficulty, hypotonia and failure to thrive. Higher maternal age may be a risk factor of PWS, especially for UPD. Further studies are needed for elucidating the mechanism of PWS.

Quality of life in caregivers of young children with Prader-Willi syndrome.

BACKGROUND: This study aimed to measure quality of life (QOL) in primary caregivers of young childrenwith Prader-Willi syndrome (PWS). METHODS: The caregivers of 32 children aged from 6.1 to 71.2 months completed the Chinese version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF). We also evaluated the social adaption capacity of these children with Infants-Junior Middle School Students' Social-Life Abilities Scale. Correlation test was used to explore the related factors to caregivers' QOL. RESULTS: Caregivers of young children with PWS had significantly lower QOL. The correlation analyses revealed that caregivers' QOL was lower in children with young age, combined diseases or symptoms or poor social adaption, or caregivers having concerns about the child. CONCLUSIONS: Rearing a chilld with PWS may lead to decreased QOL. Psychological status of caregivers should be highlighted and social support should be given to families with PWS children.

Major depressive disorder in an adolescent with Turner syndrome: a case report.

Turner syndrome (TS) is a chromosomal abnormality, of which the presence and impact of coexisting psychiatric morbidity has received little attention. The present report describes an adolescent with mosaic karyotype TS who had major depressive disorder with the predisposing cause of psychosocial burden, and relieved with the treatment of sertraline and complete remission with combined use of estradiol valerate. The report suggests us to pay more attention on the mood disorders in children with TS, especially in adolescents. For treatment aspect, medications for improving the puberty development and short stature should be added to in addition to antidepressants if they had mood disorders.

Cytogenetic and Clinical Features in Children Suspected With Congenital Abnormalities in 1 Medical Center of Zhejiang Province From 2011 to 2014.

This study aimed to investigate the detection rate of chromosome abnormalities in children suspected with congenital disorders in 1 single center, identify any differences according to different classification criteria, and try to enlighten the medical professionals what clinical features should be transferred for cytogenetic analysis.From January 1, 2011 to March 31, 2014, children who were suspected with chromosomal disorders were included. All the cytogenetic analyses were performed in the Medical Biology and Genetic Department Laboratory in Zhejiang DIAN Diagnostics. We evaluated the variants of clinical indications, and incidence and types of chromosomal abnormalities among groups.During the study period, 4129 samples were collected and analyzed. Among them, 769 children were detected with chromosome abnormalities, accounting for 18.62% of all referral cases. The ratio of sex-linked chromosomal abnormalities to autosomal ones was 1:3.2. The detection rates were 19.66% (365/1857) for boys and 17.78% (404/2272) for girls. Most of trisomy 21 were found before the age of 1 year old, while most of children with Turner syndrome were found after 6 years old. The group presenting with specific clinical stigmata had highest detection rate of 59.1%.We demonstrated the detection rates of chromosome abnormalities in children who were suspected with chromosomal disorders. Combined with previous report, we established a database of common chromosomal anomalies and the clinical features that could be useful for genetic counseling and remind the medical professionals what kind of patients should be transferred to genetic analysis.

Prevalence of obesity and overweight among Chinese children with attention deficit hyperactivity disorder: a survey in Zhejiang Province, China.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is often comorbid with psychiatric and developmental disorders. This study aimed to investigate the prevalence of obesity and overweight among Chinese children with ADHD, and to explore which subtypes of the disorder may specifically be associated with obesity/overweight. METHODS: Children meeting the DSM-IV criteria for ADHD were enrolled in the study. Weight, weight z-score, height, height z-score, BMI, and BMI z-score were used to evaluate growth status. Obesity and overweight were determined using the National Growth Reference for Chinese Children and Adolescents. Relations between the prevalence of obesity/overweight and different ADHD subtypes and pubertal development were analyzed. RESULTS: A total of 158 children with ADHD (mean age: 9.2 years) were recruited for the study. The prevalences of obesity, overweight, and combined obesity/overweight were 12.0%, 17.1%, and 29.1%, respectively, which were significantly higher than in the general Chinese population (2.1%, 4.5%, and 6.6%, respectively). Multivariable analysis showed that the children with the combined subtype of ADHD and the onset of puberty were at a higher risk of becoming obese or overweight. CONCLUSIONS: The prevalence of obesity in Chinese children with ADHD is higher than that of the general population. Children with the ADHD combined subtype who were at the onset of puberty were more likely to be overweight or obese.

ECMO support in a child with acute fulminant myocarditis.

An 11-yr-old boy with acute fulminant myocarditis was treated with routine medical therapy (antibiotics, inotropic and vasosactive agents, etc.) for 5 days, but exacerbated. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated 39 h after admission to the intensive care unit (ICU). Twenty-four hrs after ECMO, urine volume and blood pressure (BP) improved significantly. After treatment with ECMO for 140 h, the patient's ejection fraction (EF) increased to 45%, BP because normal and urine volume maintained at about 100 ml/h. So, the patient was weaned from the ECMO. The patient was discharged from the hospital on 23rd day post admission, when EF improved to 72% and with normal chest radiograph, echocardiography results and hemodynamics.