Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders.

INTRODUCTION: Aneuploids, copy number variations (CNVs), and single nucleotide variants in specific genes are the main genetic causes of developmental delay (DD) and intellectual disability disorder (IDD). These genetic changes can be detected using chromosome analysis, chromosomal microarray (CMA), and next-generation DNA sequencing techniques. Therefore; In this study, we aimed to investigate the importance of CMA in determining the genomic etiology of unexplained DD and IDD in 123 patients. METHOD: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome. RESULTS: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123). CONCLUSION: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended.

Family Physicians' Awareness of Autism Spectrum Disorder: Results from a Survey Study.

AIM: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. Family physicians with the first medical contact of children are among the most frequent physicians with ASD. We aimed to investigate family physicians' awareness of ASD. METHODS: This study was carried out family physicians in between September 25-October 15, 2018. The questionnaire form on autism awareness prepared by the researcher was delivered to family physicians electronically and in printed form, and it was filled out by volunteers. RESULTS: Forty-eight family physicians with an average professional experience of 16.9 ± 8.8 years participated in the study. A group of 66.7% of the participants had not previously received education on ASD, and 70.8% of them did not refer any child to child psychiatry with suspected ASD in the last 6 months. The participants stated that the most common clinical features in children with ASD were the inability to make eye contact (72.9%) and repetitive movements (47.9%), and 56.3% of them stated one or more features that are not observed in ASD. The compliance of the participants' answers about the clinical features observed in children with ASD with the DSM-5 criteria was determined to be 54.6 ± 18.4%. Significantly higher compliance rates were observed in the participants with education on autism and those working as a physician below 15 years. CONCLUSION: In our study, family physicians' awareness of ASD was not found to be adequate. Education programs on autism awareness should be applied to family physicians who are probably the most frequently encountered physicians by children with ASD.

Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders.

AIM: The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduplication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization. METHODS: Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood. RESULTS: According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). CONCLUSION: The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD.

Satisfaction with Life among Mothers of Pediatric Cochlear Implant Candidates: The Impact of Implant Operation and Sociodemographic Factors.

OBJECTIVES: To evaluate the satisfaction with life among mothers of pediatric cochlear implant candidates regarding implant surgery and sociodemographic factors. MATERIALS AND METHODS: Mothers of 160 pediatric patients with profound sensorineural hearing loss who underwent unilateral cochlear implant surgery were included. A questionnaire form with items on sociodemographic-familial characteristics and Satisfaction with Life Scale (SWLS) was employed via face-to-face interview method before and 12 months after the implant surgery. RESULTS: The SWLS scores significantly improved after the implant surgery [from 19.1 (7.0) to 28.9 (4.0), p<0.000]. Being unemployed vs. employed [17.9 (6.9) vs. 24.0 (5.3), p=0.000], having another child with hearing disability [13.5 (5.7) vs. 19.7 (6.9), p=0.001], younger (12-24 months) vs. older (>24 months) age of the child at the time of implant surgery [7.1 (0.4) vs. 19.7 (6.6), p=0.001], absence vs. presence of regular follow-up visits [13.0 (0.0) vs. 19.4 (7.1), p=0.002], and presence vs. absence of change in social life after the diagnosis of disease [17.3 (6.5) vs. 20.9 (7.1), p=0.001] were associated with significantly lower SWLS scores among mothers. SWLS scores were positively correlated with patient's age at the time of implant surgery (r=0.206, p=0.009), whereas negatively correlated with the number of household members (r=-0.406, p=0.000) and number of children (r=-0.310, p=0.000). CONCLUSION: In conclusion, our findings revealed the association of cochlear implantation with a significant increase in mother's life satisfaction, despite the unemployment, presence of another child with hearing disability, and crowded household. Our findings emphasize on the consideration of family systems with special attention to mother's emotional experiences and occupational competence in the intervention programs.

Assessment of Psychiatric Comorbidity and WISC-R Profiles in Cases Diagnosed with Specific Learning Disorder According to DSM-5 Criteria.

INTRODUCTION: In this study, the frequency of psychiatric comorbidity in children and adolescents who were diagnosed with specific learning disorder, the factors that affect the frequency of comorbidity, the subtypes of specific learning disorder and the effects on cognitive profile have been investigated. METHODS: Our study was performed among 80 cases with the age range 6-15 years who diagnosed with specific learning disorder Child and Adolescent Psychiatry Department between January and June 2015. In the study, DSM-IV Based Screening and Evaluation Scale for Child and Adolescent Behavioral Disorders, Specific Learning Disability Evaluation Scale and the WISC-R test were performed. During the interview, reading-writing-math abilities evaluation list (error analysis) was performed in order to define the specific learning disorder subgroup and to evaluate the detailed error profile of the specific learning disorder subgroup. Kiddie Schedule for Affective Disorders and Schizophrenia for School-age Children-Present and Lifetime Turkish Version (KSADS) was performed to detect psychiatric comorbidity diagnoses. RESULTS: 92.5% of the cases have a comorbid psychiatric disorder. The most frequent psychiatric comorbidity was attention deficit hyperactivity disorder (82.3%), followed by specific phobia (46.3%), oppositional defiant disorder (26.3%), enuresis (25%) and tic disorders (22.5%). Psychiatric comorbidity is detected more often in patients with specific learning disorder accompanied by attention deficit and hyperactivity disorder. The most frequent subtype of specific learning disorder is combined type disorder consisting of reading, writing and math disorder (37.5%). The WISC-R score of the patients who had math disorder were found to be lower than the others, and also it was detected that they learned reading and writing later, and have more comorbid psychiatric disorders. CONCLUSION: The results of our study indicate that associated psychiatric disorders are frequent with specific learning disorder. Specific learning disorder should not be considered as a single disorder, but should be assessed and treated with comorbid psychiatric disorders.

Association between Beta-Sympathomimetic Tocolysis and Risk of Autistic Spectrum Disorders, Behavioural and Developmental Outcome in Toddlers.

AIM: To investigate whether maternal intravenous beta-mimetic tocolytic therapy increases the risk of autistic spectrum disorders (ASD) and poorer behavioural and developmental outcomes. METHOD: Our study is a prospective case-control study among 90 children between 1.5 and three years old. Cases (n = 46) were toddlers with betamimetic tocolytic exposure; control group toddlers (n = 44) were tocolytic untreated. Treated and untreated groups were also divided into subgroups: term and preterm delivered. The gestational age of tocolytic treatment start, the dose and duration of exposure in hours were obtained from obstetric medical records. The Brief Infant-Toddler Social and Emotional Assessment (BITSEA), the Modified Checklist for Autism in Toddlers (M-CHAT) and the Denver Developmental Screening Test (DDST) tests were applied for evaluation of social, emotional problems, autism and developmental disorders. RESULTS: Term and preterm born toddlers treated tocolytically in utero didn't demonstrate a higher risk of autistic disorders or poorer behavioural and developmental results than controls. In the preterm group, the earliest start of tocolytic treatment was correlated with toddlers lower score of the Competencies Scale (p = 0.009) and a higher score of the Problems Scale (p = 0.048). Also, we concluded that preterm membrane rupture was associated with higher ASD risk in the untreated group (p = 0.043). CONCLUSION: Exposure to betamimetics during pregnancy was not associated with an increased risk of autism, behavioural and developmental disorders.