9. early human development

• Teratology


  The study of abnormalities of physiological development
• Teratological conditions


  • Manifestations of signaling defects in development
• Down Syndrome


  A genetic disorder caused by the presence of an extra copy of chromosome 21
• Down Syndrome


  • Intellectual disability
  • Specific facial features
  • Congenital heart defects
• Developmental Impact of Down Syndrome


  Reduced brain volume, learning and memory deficits
• Incidence of Down Syndrome
• Mouse models used to study Down Syndrome


  • Ts65Dn mouse model shows altered craniofacial development and learning deficits
• Therapeutic Approaches for Down Syndrome


  • Neuroprotective peptides to improve developmental milestones
  • Compounds like picrotoxin and pentylenetetrazole to enhance cognition
  • Anti-depressants like fluoxetine to stimulate neurogenesis
• Genetic Causes of Down Syndrome


  • Trisomy 21 (extra copy of chromosome 21)
  • Chromosomal translocations leading to extra chromosome 21 material
• Down Syndrome affects brain development, cognitive abilities, and organ systems
• Incidence of Birth Defects (USA)


  • Heart and circulation: 1 in 115 births
  • Muscles and skeleton: 1 in 130 births
  • Clubfoot: 1 in 735 births
  • Cleft lip/palate: 1 in 930 births
  • Genital/urinary tract: 1 in 135 births
• Observation and Description in Developmental Biology


  • Leonardo da Vinci: Noted normal and abnormal human development
  • Modern Research: Uses observation to understand genetic and environmental factors in developmental disorders
• Diagnostic Tests for Down Syndrome


  • Amniocentesis: Collects amniotic fluid for chromosomal analysis
  • Chorionic villus sampling: Tests fetal cells from placental tissue
  • Blood tests: Detect markers like alpha fetoprotein for risk assessment
• Heart Defects in Down Syndrome


  • Atrioventricular canal defects
  • Ventricular septal defects
  • Patent ductus arteriosus
• Mouse models show similar cardiac anomalies for Down Syndrome research and treatment development
• Neurodevelopmental Disorders


  Neurodevelopmental disorders are a group of conditions characterized by impairments in the growth and development of the brain or central nervous system
• Examples of Neurodevelopmental Disorders


  • Autism spectrum disorder (ASD)
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Intellectual disability (ID)
  • Specific learning disorders (SLD)
• Genetic Causes of Developmental Disorders

  • Chromosomal Abnormalities: Conditions like Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), and Patau syndrome (Trisomy 13) result from an abnormal number of chromosomes
  • Single Gene Mutations: Disorders such as Fragile X syndrome, Rett syndrome, and Duchenne muscular dystrophy are caused by mutations in a single gene
• Therapeutic Approaches for Neurodevelopmental Disorders


  • Behavioral Therapy: Techniques like applied behavior analysis (ABA)
  • Medication: Psychotropic medications, including stimulants for ADHD or antipsychotics for behavioral issues
  • Early Intervention Programs: Programs that provide early developmental support and therapies
• Examples of Mouse Models in Research


  • Ts65Dn mouse model for Down syndrome
  • Fragile X knockout mouse model for Fragile X syndrome
  • BTBR mouse model for autism research
• Diagnostic Tests for Down Syndrome


  • Prenatal Screening: Tests like non-invasive prenatal testing (NIPT) and ultrasound can detect markers associated with Down syndrome
  • Confirmatory Tests: Amniocentesis and chorionic villus sampling (CVS) are invasive tests that provide a definitive diagnosis by analyzing fetal cells
• Heart Defects in Down Syndrome


  • Atrioventricular canal defects
  • Ventricular septal defects (VSD)
  • Patent ductus arteriosus (PDA)
• Surgical interventions may be required to address heart abnormalities in Down Syndrome, depending on their severity
• Impact of Research Collaboration

  • Collaborative research efforts involving multiple institutions and researchers worldwide have led to significant advancements in understanding and treating developmental disorders
  • Pooling large datasets and sharing research findings globally accelerates progress in identifying genetic causes, developing therapies, and improving outcomes for affected individuals
• Intellectual Disability (ID)


  Intellectual disability refers to significant limitations in intellectual functioning (IQ below 70) and adaptive behavior, which typically manifest before the age of 18
• Causes of Intellectual Disability


  • Genetic conditions
  • Prenatal exposure to toxins or infections
  • Complications during childbirth
  • Environmental factors
• Autism Spectrum Disorder (ASD)


  ASD is characterized by difficulties in social interaction, communication challenges, repetitive behaviors, and sometimes, intellectual disabilities
• Genetic factors play a significant role in ASD, with multiple genes and genetic variations implicated in its development
• Attention-Deficit/Hyperactivity Disorder (ADHD)


  ADHD is characterized by inattention, hyperactivity, and impulsivity, which can impact academic performance, social interactions, and daily functioning
• Treatment for ADHD


  • Behavioral therapy
  • Medication (such as stimulants)
  • Educational interventions
• Types of Genetic Tests

  • Chromosomal microarray analysis (CMA)
  • Whole-exome sequencing (WES)
  • Targeted gene sequencing
• Early Intervention Programs


  Early intervention programs provide specialized support and therapies to infants and toddlers with developmental delays or disabilities to enhance their development and learning
• Components of Early Intervention Programs

  • Speech therapy
  • Occupational therapy
  • Physical therapy
  • Family support services
• Genetic Counseling


  Genetic counselors assess familial risks, explain genetic test results, and provide guidance on inheritance patterns, recurrence risks, and available reproductive options
• Genetic counseling helps individuals and families make informed decisions about family planning, prenatal testing, and managing genetic conditions
• Pharmacogenomics


  Pharmacogenomics is the study of how genetic variations influence an individual's response to medications, including dosage requirements, efficacy, and potential side effects
• Understanding pharmacogenomics helps tailor medication regimens for individuals with developmental disorders based on their genetic profiles for optimal treatment outcomes
• Behavioral Interventions


  • Applied Behavior Analysis (ABA)
  • Social Skills Training
• Applied Behavior Analysis (ABA)

  ABA is a structured therapy that uses positive reinforcement to teach and reinforce desired behaviors while reducing challenging behaviors in individuals with developmental disorders
• Social Skills Training


  Programs focusing on social skills development help individuals improve communication, social interactions, and emotional regulation