LMCC REVIEW: PEDIATRICS PART II AND DEVELOPMENT PEDIATRICS

1. LMCC REVIEW:PEDIATRICS PART IIAND DEVELOPMENT PEDIATRICS Asha Nair, MD, FRCPC Developmental Pediatrician CHEO/OCTC

2. GENETICS

3. General • Major anomalies in 3% of nb (CHD, SB, CL) • recurrence risk is 3-5% • Minor anomalies in 15% (toes/fingers) • Mechanisms of anomalies • Malformations (defect of organ from abN dev’t process) • Deformation (abN form,shape or position) from mechanical forces • Disruption (defect from extrinsic breakdown or interference with an original developmental process)

4. Dysmorphology (cont.) • Patterns of malformation include syndrome, sequence and association • SYNDROME: a pattern of anomaly due to a single/specific cause ie Marfan, Down, FAS • SEQUENCE: an underlying anomaly giving rise to a cascade of secondary problems ie Pierre Robin • ASSOCIATION: nonrandom combination of anomalies that occur together more frequently than expected by chance ie VACTERL

5. Teratogens • Drugs: • Thalidomide – phocomelia • DES - vaginal adenocarcinoma • Tetracycline - staining of teeth/bone • Retinoic acid - brain/ear/heart • Testosterone – virilization • Alcohol: FAS • Congenital infections (TORCH, varicella, parvovirus) • Metabolic conditions (maternal diabetes, PKU)

6. Patterns of Inheritance • Autosomal dominant • Autosomal recessive • X-Linked recessive • Multifactorial

7. Chromosomal Abnormalities • Aneuploidy/ Polyploidy: indicates an extra or missing chromosome • Trisomies or monosomies • Abnormalities of Chromosome structure • Deletions • Translocations • Inversions • Duplications • Sex Chromosome Anomalies

8. Down Syndrome Inheritance • nondysjunction (Trisomy) ; 95% • translocation (14/21 or 21/21) = 4 % • mosaics = 1 %

9. DOWN SYNDROME • Most common chromosomal abnormality • 1/600-1/800 live births (increases with increasing maternal age) • Features: • Flat occiput/brachycephaly, microcephaly • Epicanthal folds, upslanting palpebral features, Brushfield spots • Midface hypoplasia, small low set ears, protruding tongue • Clinodactyly, wide space between 1 and 2 toe, Simian Crease • Generalized hypotonia, intellectual disability

10. DOWN SYNDROME: Associated Medical Issues CNS : • hypotonia, Intellectual disability Ophthalmologic: • cataracts, nasolacrimal duct obstruction, strabismus, refractive errors ENT: • acute and chronic serous OM and hearing loss, chronic sinusitis, tonsillar and adenoidal hypertrophy Respiratory: • OSA, chronic pneumonia CVS: • CHD in 50%

11. DOWN SYNDROME: Associated Medical Issues • GI: • duodenal atresia (double bubble sign), GERD, Hirshsprungs, constipation, oro-motor issues leading to aspiration, FTT early on and obesity in older ages. • MSK: • joint laxity, atlantoaxial instability • ENDO: • hypothyroidism (20%), Type 1 diabetes, Coeliac disease • HEME: • increased risk of leukemia

13. Turner’s Syndrome • Incidence 1/2500 • 45 XO (55%) • mosaicism (25%) • Clinical features Birth: • edema of dorsum of hands and feet • loose skin folds at nape of neck • short stature

14. Turner’s Syndrome • Clinical features (very large variability) • Childhood: • low posterior hairline* • small mandible - prominent ears • epicanthal folds - high arched palate • broad chest* -cubitum valgus (incr. carrying angle)* • hyperconvex fingernails • pigmented nevi (  with advancing age)

15. Turner’s Syndrome • Associated features • short stature* • delayed puberty* secondary to gonadal dysgenesis • CVS defects- (Coarct, bicuspid AoV)* • renal anomalies 50% • spatial perceptual difficulties • Increased risk • hearing loss - autoimmune thyroiditis • IBD - GI telangiectasia

17. Klinefelter Syndrome – 47XXY

18. Fragile X Syndrome • X-linked • Most common cause of ID in males • Caused by defect in FMR1 gene of X chromosome • Characteristic features (see diagram) • Also social difficulties and stereotypical movements (common etiology for 2ary Autism) • Females show varying degrees of MR and have less characteristic features

20. Williams Syndrome • 7q deletion • Round face with full cheeks & lips (elfin facies) • Blue eyes with stellate pattern in iris/strabismus • Calcium disturbances • Cardiac issues: most common is supravalvular aortic or pulmonary stenosis • Growth & developmental delays/varying degree of MR • Friendly/outgoing personality

22. 22 q.11.2 Deletion Syndrome, DiGeorge or Velocardiofacial • Catch 22 Syndrome ( Cardiac, Abnormal facies, Thymic, Cleft palate, Hypocalcemia) • Chromosome 22 deletion syndrome • Hypoplasia or agenesis of thymus and parathyroid glands (immune and calcium regulation issues) • Velopharyngeal abnormalities (feeding and speech) • Hypoplasia of auricle and external auditory canal • Conotruncal cardiac anomalies • Behavioral difficulties and developmental delay

24. Other Deletion Syndromes • Prader Willi (deletion in paternal chromosome 15) • Hypotonia at birth with FTT • Obesity and short stature (GH responsive) • Almond shaped eyes • Small hands/feet and hypogonadism • Mild mental retardation • Angelman (deletion in maternal chromosome 15) • “Happy Puppet” • Hypotonia • Fair hair, midface hypoplasia, prognathism • Jerky ataxic movements,seizures, uncontrollable bouts of laughter, and severe MR

26. Noonans Syndrome • AD inheritence • Low set ears, down-slanting palpebral fissures, hypertelorism, webbed neck • Cardiac anomalies: pulmonary outflow tract (pulmonary valve stenosis) • Short stature, pectus, hypotonia, joint laxity • Feeding difficulties with excessive vomiting and FTT • Features may change with age and become easier to id

27. Fetal Alcohol Syndrome • major and minor components expressed in 1-2 infants per 1000 live births • 4-6 drinks/day • 30-40% of offspring born to heavy drinkers demonstrated congenital anomalies

28. Fetal Alcohol Syndrome • Characteristics • prenatal onset and persistent growth deficiency (ht, wt, hc) • facial anomalies • short palpebral fissures • epicanthal folds • maxillary hypoplasia • micrognathia • thin upper lip

29. Fetal Alcohol Syndrome • cardiac defects especially septal defects (ASD) • poor joint mobility • mental deficiency varying borderline severe -attention and impulsivity issues (legal pblms) Fetal Alcohol Effect (FAE) • varying phenotype, can be subtle • tend to have CNS effects

31. Marfan’s Syndrome • Autosomal dominant 1/20,000 • Manifestations • tall stature • extremities extremely long (especially distal bone) • spider fingers • arm span > height

32. Marfan’s Syndrome • wrist sign • thumb and fifth finger overlap when clasped around the wrist • Steinberg thumb syndrome • thumb opposed across palm extends past ulnar border • thoracic cage deformity • pectus, pigeon chest • hyperextension joints with recurrent dislocation

33. Marfan’s Syndrome • ectopia lentis • also retinal detachment, myopia, strabismus • CVS abnormalities • aortic root dilatation • MVP • Differential diagnosis • homocystinemia • MR associated

35. VACTERL Vertebral defects Imperforate Anus Cardiac Tracheoesophageal fistula Radial and renal Limb anomalies VATER excludes cardiac and limb anomalies CHARGE Association Coloboma Heart disease Atresia of choanae Retarded growth Genital anomalies Ear anomalies Associations

36. Neurocutaneous Syndromes-Neurofibromatosis • 50% AD • Skin lesions include: • café au lait spots • Axillary or inguinal freckling • neurofibromas • Other lesions include: • Optic gliomas • Iris hamartomas (Lisch nodules) • Osseous lesions ( spheniod dysplasia)

38. Neurocutaneous Syndromes-Tuberous Sclerosis • 30% AD • Skin lesions include: • Ash leaf spots • shagreen patch • Adenoma sebacum • Café au lait • Periungal fibromas • Other associations include: • Infantile spasms • DD and MR • Calcified tubers in brain • Retinal lesions

40. Neurocutaneous Syndromes • Sturge Weber (sporadic) • Skin lesions include: port wine stain inV1, cutaneous vascular malformations • Other findings include: sz, glaucoma, hemihypertrophy, intrecranial AVM/calcifications, MR • Ataxia Telangectasia (AR) • Skin findings include: conjunctival and cutaneous telangectasia, and café au lait spots • Other findings include: Ataxia , immunodeficiencies and malignancy • Incontinentia Pigmenti(XLR) • Skin lesions include: bullae as neonates, splashes or whorls of hyperpigmentation • Other findings include: sz, DD, MR, strabismus

42. Febrile Seizures • Common: 4-5%( OM, Gastro,URTI, Roseola) • 6 months - 6 years • Simple or Atypical • Simple Febrile Seizure: • Generalized tonic-clonic seizure with no focality • Less than 15 minutes • Occurs once in 24 hour period • Must have absence of CNS infection/absence of CNS signs interictally

43. Febrile Seizures • positive family history in 60-70% • 30 % will have recurrence(more common if + FH, 1st sz < 1yr) • risk of epilepsy 2%( more common if atypical features, underlying CNS pathology or + FH epilepsy) • versus 0.5-1% in general population • Treatment • antipyretic measures • acetaminophen • sponging with tepid water • anticonvulsant therapy in rare instances

44. Breathholding Spells(Cyanotic) • 6 months - 4 years • Onset always with crying • Infant stops breathing and becomes deeply cyanotic • Limbs become rigidly extended • If prolonged, LOC occurs with occasional convulsive jerks • child becomes limp, resumes breathing • within seconds is fully alert

45. Breathholding Spells • Prognosis • benign • disappears spontaneously by school age • these kids have increased risk of vasovagal syncope in childhood

46. Pallid Attacks • Infantile syncope follows a sudden minor injury • Child starts to cry, turns pale, and LOC • Transient apnea and limpness  rapid recovery • 2o to vagal reflex overactivity  marked transient bradycardia and circulatory impairment • Benign • Disappears spontaneously by school age

47. Night Awakening Night Terror Nightmare Duration < 5 mins Short Recall No Yes Consolable No Yes Sleep stage IV REM Treatment None Nil

48. Headaches • Not usually psychosomatic in young kids • detailed hx and pe to R/O severe pathology including: • Description • Location • Associated symptoms neuro and systemic • Family history • Emotional /stressors • Vitals • Full neuro exam including CN, fundi, motor, sensory and DTR)

49. Headaches- Types • Tension • Chronic and recurrent • No prodromes • Diffuse bandlike, tight • Sometimes associated with depression/anxiety, problems at school or at home • Vascular/ Migraine • Acute, paroxysmal, recurrent • Prodromes often present/ certain triggers • Intense, pulsatile, unilateral • Neurological signs are transient • Positive family history

50. Headaches- Types • Headaches secondary to increased ICP – What we worry about! • Chronic or intermittent but increasing frequency and severity • Am headache with vomiting ( often no nausea) • Deterioration in social, school and academic prowess • Physical exam positive for strabismus, visual loss, poor pupillary response, papilledema, coordination and gait abnormalities