Pediatric Genetics, Development, and Respiratory Care Lecture

Genetic Testing & General Genomic Principles

• Genetic testing is central to pediatric diagnosis/management of heritable disorders.
  • \text{Pathophysiology}
  • DNA sequence changes (single-gene, polygenic, mitochondrial) or chromosomal abnormalities (deletions, duplications, aneuploidies).
  • May be inherited (autosomal dominant/recessive, X-linked, multifactorial) or de novo (spontaneous mutations, meiotic nondisjunction).
  • Multi-system impact: growth, development, metabolism, immunity, cognition.
  • \text{Typical Diagnostic Workflow}
  • 3-generation family pedigree.
  • Thorough physical exam (dysmorphic features, organomegaly, neuro-motor status).
  • Laboratory armamentarium:
    • Chromosome (karyotype) & microarray analysis.
    • Targeted or whole-exome/whole-genome DNA sequencing.
    • Biochemical & enzyme assays.
    • Newborn screening panels (state-mandated heel-stick blood spot).
  • \text{Treatment Principles}
  • Multidisciplinary (geneticist, nutrition, PT/OT, social work, psychology).
  • Symptom relief (pharmacologic, surgical when indicated).
  • Disease-specific interventions: dietary restriction, enzyme replacement, gene therapy, stem-cell transplant.
  • Ongoing genetic counseling: recurrence risk, prenatal testing options, psychosocial coping.
  • \text{Role of the Nurse}
  • Early recognition/red flags → timely referral.
  • Family education (testing process, consent, result interpretation, privacy/ethical concerns).
  • Coordination of specialty appointments & community resources.

Cystic Fibrosis (CF)

• \text{Etiology / Pathophysiology}
  • Autosomal-recessive mutations (>2000 identified) in CFTR gene on chromosome 7.
  • Defective chloride/Na^+ transport ⇒ thick, dehydrated secretions in airway, pancreas, GI tract, hepatobiliary tree, reproductive ducts.
  • “Triad” of obstruction – infection – inflammation perpetuates organ damage.
• \text{Clinical Manifestations}
  • Respiratory: chronic productive cough, recurrent pneumonia/bronchiectasis, digital clubbing, sinusitis, nasal polyps.
  • GI: meconium ileus at birth, malabsorption, steatorrhea, ADEK deficiency, failure to thrive.
  • Other: salty skin, delayed puberty, male infertility (congenital bilateral absence of vas deferens).
• \text{Diagnostics}
  • Universal newborn IRT screen → confirmatory sweat chloride test >60\,\text{mmol/L}.
  • DNA panel for common CFTR variants.
  • PFTs, fecal elastase, CXR/HRCT for disease burden.
• \text{Therapy}
  • Airway: chest physiotherapy, oscillatory devices, DNase, hypertonic saline, bronchodilators.
  • Infection control: culture-guided antibiotics, chronic azithromycin, vaccination.
  • Nutrition: pancreatic enzyme beads with all meals/snacks, high-calorie/high-protein diet, salt supplementation, ADEK vitamins.
  • Precision meds: CFTR modulators (ivacaftor, lumacaftor/tezacaftor/elexacaftor combos) matched to mutation class.
  • Advanced: lung transplant for end-stage disease.
• \text{Nursing Priorities}
  • Teach chest PT timing (before meals), med adherence, infection-control (segregation, hand hygiene).
  • Growth monitoring & mental-health screening.

Sickle Cell Disease (SCD)

• \text{Genetics / Patho}
  • Point mutation (Glu➔Val) in \beta-globin ⇒ HbS polymerizes when \text{pO}_2 drops.
  • Sickled RBCs → vaso-occlusion, hemolytic anemia, end-organ ischemia.
• \text{Key Presentations}
  • Pain (dactylitis, long-bone, chest syndrome).
  • Chronic hemolysis: jaundice, gallstones, delayed growth/puberty.
  • Infection risk (functional asplenia) ⇒ sepsis/meningitis.
  • Cerebrovascular: silent infarcts, overt stroke.
• \text{Work-up}
  • State newborn screen (isoelectric focusing or HPLC).
  • Confirm with hemoglobin electrophoresis / DNA testing.
  • Baseline: CBC, retic, transcranial Doppler \le 2 yrs.
• \text{Management}
  • Prevention: penicillin prophylaxis <5 yrs, vaccines (PCV13, MenACWY, Hib, annual flu).
  • Hydroxyurea ↑ HbF production; L-glutamine, voxelotor, crizanlizumab newer agents.
  • Acute: opioids, IV hydration, O_2, antibiotics, transfusion/exchange.
  • Curative: matched sibling hematopoietic stem-cell transplant, emerging gene-editing (CRISPR-Cas9 BCL11A).
• \text{Nursing Focus}
  • Pain assessment (use developmentally appropriate scales).
  • Teach hydration, trigger avoidance (extremes temperature, high altitude).
  • Crisis plan & school 504 accommodations.

Phenylketonuria (PKU)

• Autosomal recessive deficiency of phenylalanine hydroxylase (PAH) ⇒ accumulation of phenylalanine, deficit of tyrosine.
• Untreated levels >20\,\text{mg/dL} cause irreversible intellectual disability, seizures, hypopigmentation, “musty” body odor.
• Detected on newborn blood spot (Guthrie / MS-MS).
• Lifelong low-Phe diet: medical formula, limited natural protein, Phe-free medical foods, tyrosine supplementation; BH4 (sapropterin) responsive subset.
• Nursing: detailed diet teaching, growth & neuro-psych monitoring, adolescent adherence counseling, maternal PKU management in pregnancy.

Trisomy 21 (Down Syndrome)

• Extra chromosome 21: 95\% free trisomy (meiotic nondisjunction), 4\% Robertsonian translocation, 1–4\% mosaic.
• Phenotype: upslanting palpebral fissures, epicanthic folds, single transverse palmar crease, hypotonia.
• Common comorbidities: AV canal defects, duodenal atresia, Hirschsprung, hypothyroid, atlanto-axial instability, AML-TMD, OSA, hearing/vision issues, Alzheimer-type dementia.
• Care plan: early intervention, individualized education, surveillance guidelines (AAP): echo at dx, annual TSH, sleep study by 4 yrs, ophthalmology <6 months then qyr, audiology.

Tay–Sachs Disease

• Autosomal recessive HEXA deficiency ⇒ GM2 ganglioside accumulation in neurons.
• Classic infantile onset 3–6 mo: hypotonia, motor regression, hyperacusis, cherry-red macula, seizures, blindness, macrocephaly, death \approx 4 yrs.
• Dx: absent hexosaminidase A activity; targeted sequencing esp. in Ashkenazi Jewish, Cajun, French-Canadian populations.
• No cure; focus on seizure control, nutrition, respiratory hygiene, palliative care; prenatal/pre-implantation genetic testing vital.

Galactosemia

• GALT enzyme deficiency ⇒ toxic galactose-1-phosphate buildup.
• Neonatal onset: jaundice, vomiting, failure to thrive, E. coli sepsis, cataracts.
• Management: lactose/galactose-free diet (soy-based formula), monitor Ca/Vit D, speech therapy (risk of speech dyspraxia), annual neuro-cognitive & ovarian function assessment in females.

General Concepts of Genetic Traits

• Traits may be:
  • Unifactorial (Mendelian) – cystic fibrosis, sickle cell, PKU.
  • Multifactorial – height, blood pressure, type 1 diabetes.
• Genotype = allelic constitution; Phenotype = observable expression under genetic + environmental modulation.
• Some traits benign (eye color); others confer disease risk; nursing role to clarify misconceptions about inheritance patterns & penetrance.

Type 1 Diabetes Mellitus (Autoimmune)

• Autoimmune destruction of pancreatic \beta-cells ⇒ absolute insulin deficiency.
• Classic polyuria–polydipsia–polyphagia, weight loss, DKA risk.
• Labs: random plasma glucose \ge 200\,\text{mg/dL} with symptoms, fasting \ge126, HbA_1c\ge6.5\%.
• Management: basal-bolus or pump insulin, carb counting, CGM use; no surgery typical.

Pediatric Development & Behavior

Toddlers (1–3 yrs)

• Developmental delays → early intervention (IFSP) critical.
• Temper tantrums: normal autonomy struggle; manage via consistent limits, simple choices, time-out (\ge18 mo), positive reinforcement.
• Regression during stress (hospitalization, new sibling) → offer reassurance, avoid new skill demands; praise existing skills.
• Child-Life Specialists: procedural play, coping coaching, liaison between team & family.

Preschoolers

• Milestones: rides tricycle, draws 2–4-part person, counts to 10, names colors, cooperative play, empathy, independent dressing.
• Bicycle safety: helmet every ride, traffic rules, appropriate bike size, adult supervision.
• Abuse awareness: unexplained injuries, sexualized behavior, fear of adults. Nurses = mandated reporters, provide caregiver education & resources.

Adolescents

• Language: refined pragmatic & persuasive skills; essential for resisting peer pressure & complex social navigation.
• Sexuality: spectrum exploration; provide non-judgmental, inclusive education (LGBTQ+ youth higher mental-health risk).
• Eating disorders: anorexia, bulimia, BED. Red flags—rapid weight change, food rituals, withdrawal. Multidisciplinary treatment; nurses monitor vitals, electrolytes, support family-based therapy.

Sensory & Nervous System Disorders

Otitis Media (AOM & OME)

• Often post-URI as pathogens ascend horizontal eustachian tube.
• AOM: fever, ear tugging, bulging TM. Initial analgesia; watchful waiting, then amoxicillin if no improvement; myringotomy tubes for recurrent episodes.
• OME: effusion \pm symptoms; usually self-resolves; hearing surveillance due to speech-language risk.
• Risk factors: passive smoke, bottle-feeding, daycare, allergies, adenoid hypertrophy, male sex.

Otitis Externa (Swimmer’s Ear)

• Persistent moisture ⇒ bacterial/fungal canal infection.
• Pain, otorrhea, itching. Treat with topical combo drops (antibiotic + steroid ± antifungal). Teach ear-drying techniques (alcohol–vinegar rinse, hair-dryer).

Strabismus

• Exotropia (outward) / esotropia (inward) misalignment; usually resolves by 3–6 mo infancy.
• Screen: corneal light reflex, cover-uncover test, Ishihara color plates, peripheral vision.
• Tx: glasses, contacts, atropine blurring, patching strong eye (amblyopia therapy), surgical realignment, lasers.

Eye Injuries & Disorders

• Spectrum: eyelid laceration, black eye, subconjunctival hemorrhage (painless), corneal abrasion, foreign body, hordeolum, chalazion, blepharitis.
• Basic first aid: shield eye, avoid pressure/patch for penetrating trauma, prompt ophthalmology referral.

Nasolacrimal Duct Obstruction

• Congenital stenosis; chronic tearing. Massage lacrimal sac; 90\% resolve by 1 yr; persistent cases need probing surgery.

Retinoblastoma

• RB1 “two-hit” tumor suppressor loss; leukocoria hallmark (check flash photos). Multi-modal therapy (laser, cryo, chemo, radiation, enucleation). >90\% survival when detected early. Lifelong second-malignancy surveillance in hereditary form.

Lead Poisoning & Cognitive Impact

• Blood lead \ge5\,\mu g/dL affects synaptogenesis ⇒ reduced IQ, ADHD-like behaviors, executive dysfunction. Screen high-risk 1–2 yrs; chelation when >45\,\mu g/dL.
• ADHD, Down syndrome, Fragile X all entail specific cognitive profiles nurses must recognize to tailor education strategies.

Respiratory Disorders

Croup Spectrum

• Epiglottitis (bacterial; Haemophilus influenzae type b) = airway emergency: drooling, tripod, no cough. Do not use tongue depressor; prep for intubation; IV ceftriaxone & steroids.
• Laryngotracheobronchitis (viral; RSV, parainfluenza) – barky cough, inspiratory stridor; treat with humidified air, dexamethasone, racemic epinephrine.

RSV Prevention

• Hand hygiene, palivizumab for high-risk infants (premature, CHD), smoke avoidance, droplet/contact isolation.

Airway Obstruction

• Etiologies: inflammation, foreign body, anaphylaxis, trauma, congenital malacia.
• Assess: stridor, retractions, cyanosis, pulse-ox, seesaw respirations.
• Interventions: calm positioning, O_2, prepare advanced airway.

Asthma

• Chronic inflammatory disease with airway hyper-responsiveness.
• Triggers: allergens, viral infection, exercise, smoke, cold air.
• Assessment: wheeze, cough, chest tightness, accessory muscle use, decreased peak flow.
• Dx: spirometry (FEV_1), bronchodilator reversibility, allergy testing.
• Pharmacology hierarchy:
  • Rescue: short-acting \beta_2-agonists (albuterol, levalbuterol, terbutaline).
  • Control: inhaled steroids, LABA + steroid (salmeterol, formoterol), leukotriene antagonists, anticholinergics, theophylline.
• Education: spacer technique, rinse mouth post-ICS, trigger diary, action plan, peak-flow monitoring.

Tuberculosis Protocol

• Airborne isolation (negative pressure), N95, DOT (isoniazid + rifampin + pyrazinamide + ethambutol initial 2 mo then tailored continuation), monitor hepatotoxicity, contact tracing.

Pertussis

• Bordetella pertussis toxin damages cilia → catarrhal (URI) → paroxysmal “whoop” → convalescent. Vaccination (DTaP/Tdap) key; macrolide therapy; droplet isolation.

Airborne PPE Basics

• N95/PAPR, gown, gloves, eye protection, patient masking for transport, maintain until sputum cultures ×3 negative.

Influenza

• Fever, myalgia, cough; antivirals (oseltamivir) within 48 h; annual vaccine \ge6 mo age; droplet precautions.

Foreign-Body Aspiration

• Peak 6 mo–4 yrs; sudden cough, unilateral wheeze, x-ray; rigid bronchoscopy removal; postoperative antibiotics.

Allergic Rhinitis

• IgE-mediated nasal mucosal inflammation; triggers aeroallergens; comorbid with asthma/atopic dermatitis.
• S/S: congestion, rhinorrhea, sneezing, itching, mouth breathing, snoring; may cause dental malocclusion, chronic OME.
• Therapy: allergen avoidance, intranasal corticosteroids, antihistamines, leukotriene modifiers, immunotherapy.

Pharyngitis

• Viral 80–90\% vs Group A Strep (GABHS).
• Rapid antigen test; if negative but high suspicion → culture.
• Viral: supportive; GABHS: 10-day penicillin/ amoxicillin; educate completion to prevent rheumatic fever.

Ethical & Practical Implications

• Informed consent for genetic testing (child assent vs parental consent).
• Privacy: Genetic Information Nondiscrimination Act (GINA) protections.
• Psychosocial: coping with chronic illness, stigma, transition-of-care to adult providers.
• Resource equity: access to expensive CFTR modulators, gene therapies.

Quick-Reference Numerical/Stat Facts

• Sweat chloride >60\,\text{mmol/L} = CF diagnostic.
• Newborn heel-stick screens typically run at 24–48 h of life.
• Down syndrome recurrence risk in translocation carriers: up to 10–15\% (maternal) \ & 2–5\% (paternal).
• Hydroxyurea goal HbF >20–30\% reduces SCD crises by \approx50\%.
• Lead chelation threshold >45\,\mu g/dL (succimer oral) or >70 (EDTA IV).
• Peak flow personal best =100\%; green >80\%, yellow 50–80\%, red <50\% → emergency plan.