Genetic Testing in Pediatric Epilepsy: Tools, Tips, and Navigating the Traps.

With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications.

Decoding the Genetics of Recurrent Molar Pregnancy.

Hydatidiform mole is a condition characterised by abnormal trophoblastic hyperplasia and failure of embryonic tissue development. The risk of recurrence is seen to be associated with biallelic maternal mutations in , and genes. Women with such mutations have a major risk of reproductive failure and normal pregnancy is seen in only 1.

Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder.

Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care.

The molecular landscape of oculocutaneous albinism in India and its therapeutic implications.

Oculocutaneous albinism is an inherited disorder of melanin biosynthesis, characterized by absent or reduced pigmentation of the skin, hair, and eyes. Molecular alterations of genes that cause non-syndromic albinism in Asian Indians are poorly characterized. This information would be useful for developing therapies for this disorder.

A Rare Case of Mosaic 3pter and 5pter Deletion-Duplication with Autism Spectrum Disorder and Dyskinesia.

Introduction: There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of such cases. A 3 years and 11 months old boy with global developmental delay had repetitive behaviors and hyperkinetic movements.

Next-Generation Sequencing in Unexplained Intellectual Disability.

Objectives: To determine the diagnostic yield of next generation sequencing (NGS) in patients with moderate/severe/profound intellectual disability (ID) unexplained by conventional tests and to assess the impact of definitive diagnosis on the clinical management and genetic counselling of these families.

Methods: This was a ambi-directional study conducted at Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi. The study comprised 227 patients (prospective cohort - 126, retrospective cohort - 101) in whom NGS based tests were performed.

Antenatal Phenotype of Desbuquois Dysplasia.

Desbuquois dysplasia (DBQD) is an uncommon, autosomal recessive disorder with multiple joint dislocations. It is caused by pathogenic variants in CANT1 (calcium-activated nucleotidase 1) [NM_001159773.2].

Clinical and Genetic Profile of Children With Short Stature Presenting to a Genetic Clinic in Northern India.

Objective: To define the spectrum of genetic disorders in patients with short stature visiting the genetic out-patient department in a tertiary care hospital.

Methods: A chart review was done for 455 individuals (10 months-16 yrs) with short stature, who were evaluated at the genetic clinic from 1 January, 2017 upto 31 October, 2018. 226 patients who needed detailed evaluation, the spectrum of genetic diagnosis is presented.

Hypervitaminosis D and Acute Interstitial Nephritis: Tale of Injections.

A 33-year-old man came with nausea, vomiting and abdominal pain due to hypercalcaemia and renal dysfunction following two doses of intramuscular vitamin D injections. Levels of vitamin D were repeatedly above 300 ng/ml over a period of 10 months. Whole-body PET CT scan revealed a thin-walled collection in the right gluteal region.

Prenatal phenotypic spectrum of full trisomy 18 in an Indian cohort.

Trisomy 18 or Edward syndrome is a chromosomal disorder due to the presence of an extra chromosome 18. We describe the phenotype of five fetuses at different gestational ages, each highlighting a different aspect of trisomy 18. The clinical spectrum included increased nuchal translucency, fetal hydrops, congenital malformations of the central nervous system, congenital heart disease, radial ray defects, and characteristic facial gestalt.

Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II.

MPS II is an X linked recessive lysosomal storage disorder with multi-system involvement and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 144 Indian patients with MPS II from 130 unrelated families. Clinical information was collected on a predesigned clinical proforma.

Growth and neurodevelopmental disorder with arthrogryposis, microcephaly and structural brain anomalies caused by Bi-allelic partial deletion of SMPD4 gene.

Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system. Neutral sphingomyelinase type 3, encoded by SMPD4 gene has recently been reported to cause a severe autosomal recessive neurodevelopmental disorder with congenital arthrogryposis and microcephaly.

Duplication-Mediated Autosomal Dominant Adult-Onset Leukodystrophy in an Indian Family.

Autosomal dominant leukodystrophy is an adult onset neurodegenerative disorder presenting with progressive symptoms of ataxia and autonomic dysfunction in fourth or fifth decade in life. It has clinical similarity with multiple sclerosis, but shows characteristic magnetic resonance imaging findings of diffuse bilaterally symmetrical leukodystrophy which can distinguish this disorder. It is a rare disorder with no known treatment till date, and has never been described from the Indian subcontinent.

Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis.

Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.

Pathogenic variations in SMPD1 lead to acid sphingomyelinase deficiency (ASMD), that is, Niemann-Pick disease (NPD) type A and B (NPA, NPB), which is a recessive lysosomal storage disease. The knowledge of variant spectrum in Indian patients is crucial for early and accurate NPD diagnosis and genetic counseling of families. In this study, we recruited 40 unrelated pediatric patients manifesting symptoms of ASMD and subnormal ASM enzyme activity.

Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience.

Background: Karyotyping has been the gold standard for prenatal chromosome analysis. The resolution should be higher by chromosome microarray analysis (CMA). The challenge lies in recognizing benign and pathogenic or clinically significant copy number variations (pCNV) and variations of unknown significance (VOUS).

Challenges in Chronic Genetic Disorders: Lessons From the COVID-19 Pandemic.

To examine the impact of the COVID-19 pandemic, we interviewed 26 patients with lysosomal storage disorders receiving enzyme replacement therapy. 20 (77 %) had significant interruption in their treatment, with an average of 8 (range 2-28) missed doses. Alternate methods of delivering uninterrupted care including home therapy were used.