UNIT 3 - GENETICS - GENETIC TESTING IN THE NEONATES AND CHILDREN.pdf

UNIT 3 - GENETICS - GENETIC TESTING IN THE NEONATES AND CHILDREN.pdf

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  UNIT – 3 GENETICTESTING IN THE NEONATES AND CHILDREN %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% CONTENTS : Screening for o Congenital abnormalities o Developmental delay o Dysmorphism %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Definition / Introduction  Genetic testing refers to laboratory methods used to identify changes in chromosomes, genes, or proteins.  In neonates and children, it helps detect inherited disorders early, guiding treatment and counseling. Types of Genetic Testing  Diagnostic testing: Confirms or rules out a suspected genetic condition.  Carrier testing: Identifies if a child carries a gene mutation without showing symptoms.  Predictive testing: Detects risk of developing a condition later in life.  Newborn screening: Performed soon after birth to detect treatable genetic/metabolic disorders. Screening Tests A) Congenital Abnormalities  Detects structural or functional anomalies present at birth caused by genetic, environmental, or unknown factors.  Screening tests aim to detect these conditions early, often before symptoms appear, to enable timely intervention.  Examples: Down syndrome, congenital heart defects, neural tube defects.
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  a) Prenatal Screening Ultrasound (USG): Detects structural anomalies (e.g., neural tube defects, congenital heart disease).  Maternal serum screening: Measures biochemical markers (AFP, hCG, estriol) for risk of Down syndrome, trisomy 18, neural tube defects.  Non-invasive prenatal testing (NIPT): Analyzes cell-free fetal DNA in maternal blood for chromosomal abnormalities.  Amniocentesis / Chorionic villus sampling (CVS): Invasive tests for definitive diagnosis. b) Newborn Screening  Heel-prick blood test (Guthrie test): Detects metabolic disorders like phenylketonuria (PKU), congenital hypothyroidism.  Pulse oximetry: Screens for critical congenital heart disease.  Hearing screening: Detects congenital hearing loss.  Physical examination: Identifies dysmorphic features or external anomalies. B) Developmental Delay  Developmental delay refers to slower achievement of milestones in motor, language, cognitive, or social domains compared to peers.  Screening tests help identify children at risk early, enabling timely intervention.  Commonly linked to Fragile X syndrome, Rett syndrome, metabolic disorders. a) General Developmental Screening  Denver Developmental Screening Test (DDST-II): o Assesses personal-social, fine motor-adaptive, language, and gross motor skills. o Widely used for children up to 6 years.  Ages and Stages Questionnaire (ASQ): o Parent-completed tool covering communication, motor, problem-solving, and social skills.  Bayley Scales of Infant Development: o Measures cognitive, motor, and behavioral development in infants and toddlers. b) Specific Domain Screening  Language delay: Early Language Milestone Scale, MacArthur-Bates Communicative Development Inventories.  Motor delay: Peabody Developmental Motor Scales.  Cognitive delay: Griffiths Mental Development Scales.
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  c) Neurological &Genetic Evaluation  Chromosomal microarray, Fragile X testing, metabolic screening when indicated.  Neuroimaging (MRI/CT) for suspected structural brain abnormalities. C) Dysmorphism  Dysmorphism refers to abnormal physical features or variations in body structure that suggest an underlying genetic syndrome.  Screening and diagnostic tests help identify the genetic basis of these features in neonates and children.  Examples: Facial anomalies in Turner syndrome, microcephaly in microdeletion syndromes.  Evaluation: Clinical examination + genetic testing (FISH, array CGH). Clinical Evaluation  Detailed history: Prenatal, perinatal, family history of genetic disorders.  Physical examination: Careful assessment of facial features, body proportions, skin, limbs, and organ systems.  Anthropometric measurements: Head circumference, arm span, height, weight compared to standard charts.  Photographic documentation: Used for comparison with known syndromes. Laboratory & Genetic Tests  Karyotyping: Detects chromosomal abnormalities (e.g., Down syndrome, Turner syndrome).  Fluorescence in situ hybridization (FISH): Identifies microdeletions/duplications (e.g., DiGeorge syndrome).  Chromosomal microarray (CMA): Detects copy number variations.  Whole exome sequencing (WES): Identifies mutations in coding regions of genes.  Targeted gene panels: For suspected syndromes (e.g., Noonan, Williams).  Metabolic screening: If dysmorphism is associated with metabolic disorders. Functions / Importance of screening test  Early diagnosis → timely interventions and therapies.  Family counseling → informs parents about recurrence risks.  Prevention → guides reproductive decisions.  Improved prognosis → early treatment reduces morbidity.