Epidemiological predictors of quality of life and the role of early markers in children with cerebral palsy: A multi-centric cross-sectional study.

BACKGROUND: More than 100 million children in the world have at least one type of disability. Among disabled children, approximately 25% of chronic disabilities are of neurological origin. Cerebral Palsy is the leading cause of chronic disability in children, making them not only physically and mentally handicapped but also socially aloof. METHODS: This study was conducted among 200 eligible participants from three centers with Child Guidance or Cerebral Palsy clinics in the outpatient department. All the participants were included in the analysis of the epidemiological profile and the role of early markers. Of these, 70 participants were assessed for quality of life according to the age criteria of a pre-tested Cerebral Palsy Quality of Life questionnaire (CP-QOL). RESULTS: Mean ± S.D. age in years was 3.7 ± 2.8. Birth history included 182 (39%) neonatal etiopathology, followed by 173 (38%) perinatal, and 106 (23%) antenatal causes. Mean ± S.D. birth weight was 2.3 ± 1.2 kg. The positive predictors of various domains of Quality of Life were an absence of any associated sensory, neurological, communication, or psychological disorder or disability. While, the negative predictors were decreasing functional capacity, involvement of number of limbs in increasing order, high therapeutic requirements, and dependency. CONCLUSION: The association between early diagnosis of cerebral palsy and improved functional capacity, involvement of a lesser number of limbs, better quality of life, and absence of associated disabilities is established from the findings of our study.

Proband only exome sequencing in 403 Indian children with neurodevelopmental disorders: Diagnostic yield, utility and challenges in a resource-limited setting.

Whole exome sequencing is recommended as the first tier test for neurodevelopmental disorders (NDDs) with trio being an ideal option for the detection of de novo variants. Cost constraints have led to adoption of sequential testing i.e. proband-only whole exome followed by targeted testing of parents. The reported diagnostic yield for proband exome approach ranges between 31 and 53%. Typically, these study designs have aptly incorporated targeted parental segregation before concluding a genetic diagnosis to be confirmed. The reported estimates however do not accurately reflect the yield of proband only standalone whole -exome, a question commonly posed to the referring clinician in self pay medical systems like India. To assess the utility of standalone proband exome (without follow up targeted parental testing), we retrospectively evaluated 403 cases of neurodevelopmental disorders referred for proband-only whole exome sequencing at Neuberg Centre for Genomic Medicine (NCGM), Ahmedabad during the period of January 2019 and December 2021. A diagnosis was considered confirmed only upon the detection of Pathogenic/Likely Pathogenic variants in concordance with patient's phenotype as well as established inheritance pattern. Targeted parental/familial segregation analysis was recommended as a follow up test where applicable. The diagnostic yield of the proband-only standalone whole exome was 31.5%. Only 20 families submitted samples for follow up targeted testing, and a genetic diagnosis was confirmed in twelve cases increasing the yield to 34.5%. To understand factors leading to poor uptake of sequential parental testing, we focused on cases where an ultra-rare variant was detected in hitherto described de novo dominant neurodevelopmental disorder. A total of 40 novel variants in genes associated with de novo autosomal dominant disorders could not be reclassified as parental segregation was denied. Semi-structured telephonic interviews were conducted upon informed consent to comprehend reasons for denial. Major factors influencing decision making included lack of definitive cure in the detected disorders; especially when couples not planning further conception and financial constraints to fund further targeted testing. Our study thus depicts the utility and challenges of proband-only exome approach and highlights the need for larger studies to understand factors influencing decision making in sequential testing.

Spectrum of Common and Rare Small Molecule Inborn Errors of Metabolism Diagnosed in a Tertiary Care Center of Maharashtra, India.

Introduction Inborn errors of metabolism (IEM) form a large group of genetic diseases involving defects in genes coding for enzymes, receptors, and cofactors in the metabolic pathways of small and large molecules. The present study is the comprehensive data analysis of the tandem mass spectrometry (TMS) and urine metabolic pattern for the diagnosis of IEMs by gas chromatography and mass spectrometry (GC/MS) in samples received for high-risk IEM screening. Methods We conducted a retrospective analysis of children diagnosed with IEMs presenting at the genetic clinic of Mahatma Gandhi Missions (MGM) Medical College, Aurangabad. This article summarizes retrospective data of 40 pediatric cases over a three-year period, diagnosed with small molecule IEM based on the standard testing criteria. Results Out of 40, 17 patients (42.5%) were found to have organic acidemias, four (10%) had fatty acid oxidation defects, six (15%) had disorders of aminoacidopathies, seven (17.5%) had mitochondrial diseases, and three (7.5%) had urea cycle defects. One patient in each group (2.5% each) had carbohydrate metabolism defects, purine metabolic defects, and neurotransmitter metabolic defects. Conclusions This clinico-etiological profile study has thrown light on the clinical features and natural course of many common and rare IEMs, and it may provide clinicians with a deeper understanding of these conditions, allowing for improved early diagnosis and treatment of these diseases. Because of the high degree of consanguinity and marriages in the same community, common as well as many rare inherited metabolic diseases were diagnosed and novel genetic variants were identified.

Assessment of school readiness of children and factors associated with risk of inadequate school readiness in Ujjain, India: an observational study.

OBJECTIVE: School readiness is a condition or state indicating that the child is ready to learn in a formal educational set-up. The objective of this study was to estimate the prevalence of and factors associated with school readiness in urban schoolchildren in Ujjain, India. METHODS: This cross-sectional study was conducted from February 2016 to March 2017. Two English-medium schools were conveniently selected. All children aged 5-7 years were eligible to participate. A subscale of Differential Ability Scales-Second Edition, namely 'school readiness scale', was used to assess school readiness in three major domains-early number concept, matching letter-like forms and phonological processing. Data on factors associated with school readiness were collected through parent interview. Quantile regression analysis was used to explore school readiness scores. RESULTS: This study included 203 school-going children (105 boys and 98 girls) having a mean (SD) age of 67.7 (±0.51) months. The phonological processing and matching letter-like forms had 31.5% and 30.5% children, respectively, in lower quantiles (≤25th). The higher quantile (≥75th) scores were achieved for phonological processing and early number concept (47.7% and 44.8% children, respectively). The results of quantile regression showed negative association of school readiness scores with age of children, lower socioeconomic status and hospitalisation status, especially in the lower quantiles (≤25th). The 10th, 50th and 75th quantile scores were positively correlated with the increasing education status of the mother. Birth weight was positively associated with the median and higher quantile scores (≥75th). CONCLUSIONS: School readiness in a middle-class urban setting in India was negatively associated with lower age of the child, lower socioeconomic status, hospitalisation and positively correlated with increasing birth weight and maternal education. Lower quantile scores were achieved in matching letter-like forms, which measures complex visual-spatial processing, and phonological ability, which correlates with acquired verbal concepts. Focused interventions are needed to improve these skills.