Search

Chromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge's syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman's and Prader–Willi's syndromes). Also, 3.0% (10/332) of patients were positive for Williams–Beuren's syndrome 7q11.23, 1.8% (6/332) for Wolf–-Hirschhorn's syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.

COVID 19 has already affected more than 191 million people worldwide and has claimed more than 4 million lives to date (22nd July 2021). Yet, we still do not completely understand this disease. Data on children are even more sparse, making it difficult to lay down a comprehensive guideline for the same. However, thanks to a handful of studies, we now understand that children are less affected, are less infectious, have lesser mortality and risk of complications. Children with underlying chronic diseases and infants under 1 year are especially at risk and are advised selective shielding. Diagnosis is done by RT-PCR or serology, just like in adults. Most affected children are asymptomatic, and even the symptomatic children have a good outcome and usually need supportive management and monitoring only. Up to 7% of children were found to require PICU support, and mortality was less than 2%. Most deaths were attributed to underlying conditions and immunological complications, especially MIS-C. Treatment is predominantly supportive, with little consensus on specific treatments, including corticosteroids, remdesivir, and IVIg. Management is best individualized by a multidisciplinary team involving pediatricians, hematologists, immunologists, and intensivists. Prevention of COVID 19 can be achieved by proper hygiene, face masks, and social distancing. The upcoming vaccines are expected to bring down the cases and hopefully bring this pandemic to a halt.

Disease chronicity, lifelong medications, Adrenal crisis, and genital surgeries affect the physical, mental, school and social aspects of a child's life and are a cause of great concern to parents regarding the future of their child with Congenital Adrenal Hyperplasia (CAH). The aim of the study was to assess quality of life (QoL) in children and parents of CAH and comparison with healthy children.This was a questionnaire-based cross-sectional study in 28 children with classical CAH attending the Pediatric Endocrine clinic at a tertiary-care center in northern India.CAH children had poorer QoL in School domain (73.6 vs. 90.0; p = 0.034) and significantly lower scores than their healthy peers in General (83.1 vs. 91.7, p = 0.025), Sleep (74.4 vs. 84.2, p = 0.017) domains and total score (80.0 vs. 87.8, p = 0.008) of the Fatigue scale. Parents reported Social (72.4 vs. 84.5; p = 0.009), School (63.8 vs. 90.0; p 0.01) and Total (74.3 vs. 84.2; p = 0.024) QoL were scores significantly lower than parents of healthy children. Parents perceived scores of Fatigue scale were significantly worse in all domains when compared to parents of healthy children. Failure to thrive was found to be a significant risk factor for impaired school (r = -0.533; p = 0.013) and overall (r = -0.563; p = 0.008) QoL as perceived by the child.Children and parents have different perception of QoL for their child. Routine periodic QoL assessment will help in better understanding of child and parent's hidden concerns which remain unaddressed in busy clinical practice.

Chromatinopathy is an emerging category of multiple malformation syndromes caused by disruption in global transcriptional regulation with imbalances in the chromatin states (i.e., open or closed chromatin). These syndromes are caused by pathogenic variants in genes coding for the writers, erasers, readers, and remodelers of the epigenetic machinery. Majority of these disorders (93%) show neurological dysfunction in the form of intellectual disability. Other overlapping features are growth abnormalities, limb deformities, and immune dysfunction. In this study, we describe a series of children with six common chromatinopathy syndromes with an aim to develop pattern recognition of this emerging category of multiple malformation syndromes

To characterize the CYP21A2 gene mutations in children with classic congenital adrenal hyperplasia (CAH).A prospective, cross-sectional study was conducted on 24 children with classic CAH. Molecular characterization of the CYP21A2 gene was carried out by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), or clinical exome sequencing. Another 21 previously mutation-proven CAH patients were also included and a combined result was drawn.Out of 45 children, pathogenic variants in the CYP21A2 gene were identified in 43 patients (95.5%). Homozygous, probable compound heterozygous, and heterozygous variants were seen in 69%, 22%, and 18% of patients, respectively. The most common variant was c.293-13C/AG (33%), followed by deletion/duplication (24%), and c.955CT (p.Gln319Ter) (21%), similar to previous Indian studies. Allelic frequencies of c.332_339del and c.518 TA (p.Ile173Asn) were 9% and 4%, respectively. Less common variants were c.923dupT (p.Leu308PhefsTer6), c.92CT (p.Pro31Leu), c.1069CT (p.Arg357Trp), c.1267GC (p.Gly423Arg), and c.710_719delins (p.Ile237_Met240delinsAsnGluGluLys). A good genotype-phenotype correlation was observed; only p.Pro31Leu and p.Ile173Asn variants showed discordance. The diagnostic yield of Sanger sequencing alone, Sanger sequencing with MLPA, and clinical exome alone was 85%, 100%, and 100%, respectively.All children, except two, diagnosed clinically as classic CAH, showed pathogenic variants in the CYP21A2 gene; the most common variant was c.293-13 C/AG. The results suggest a broad mutation spectrum in the authors' single-center cohort of children with CAH. Clinical exome sequencing is the preferred stand-alone method for molecular diagnosis of CAH.