genetics 1

Question 1

Trisomy 21 (Down syndrome): key neonatal features

Answer 1

⭐ Hypotonia (most consistent), flat facies, upslanting palpebral fissures, epicanthal folds, Brushfield spots | ⭐ Single palmar crease, sandal gap toe | ⭐ Duodenal atresia (‘double bubble’); Hirschsprung disease | ⭐ CHD ~50% — AVSD most common in T21 | Risk: ALL (10-20x), hypothyroidism, atlantoaxial instability | 🔑 Flat occiput + excess nuchal skin + protruding tongue + small ears

Question 2

Trisomy 18 (Edwards): key features and prognosis

Answer 2

⭐ Overlapping fingers: index over 3rd, 5th over 4th — PATHOGNOMONIC | ⭐ Rocker-bottom feet, clenched fists, prominent occiput | ⭐ VSD most common CHD; omphalocele, horseshoe kidney, single umbilical artery | IUGR, polyhydramnios, strawberry skull on prenatal US | ⭐ 50% die by 1 week; 90% by 1 year | 🔑 Overlapping fingers + rocker-bottom feet = T18 until proven otherwise

Question 3

Trisomy 13 (Patau): key features

Answer 3

⭐ Holoprosencephaly + cyclopia/hypotelorism + midline cleft lip/palate | ⭐ Postaxial polydactyly — KEY differentiator from T18 | ⭐ Cutis aplasia (scalp defects) — nearly pathognomonic | Microphthalmia, coloboma; CHD 80% (VSD, ASD, PDA) | ⭐ Median survival 7-10 days; 90% die within 1 year | 🔑 Midline defects + polydactyly + cutis aplasia = T13

Question 4

Turner syndrome (45,X): neonatal presentation

Answer 4

⭐ Lymphedema of dorsum of hands/feet — most common neonatal sign | ⭐ Webbed neck, shield chest, widely spaced nipples, low posterior hairline | ⭐ Bicuspid aortic valve (~30%); coarctation of aorta (~10%) | ⭐ Horseshoe kidney; streak gonads -> primary amenorrhea | Short stature; normal verbal IQ but visuospatial difficulties | 🔑 Puffy feet in a female newborn -> check karyotype

Question 5

Klinefelter (47,XXY): features

Answer 5

⭐ Usually NOT diagnosed in neonatal period | May have small testes, micropenis, hypospadias | ⭐ Later: tall stature, long limbs, gynecomastia, small firm testes | Infertility (azoospermia), testosterone deficiency, language-based LD | Most common sex chromosome disorder in males (~1:600) | 🔑 Tall male + small testes + infertility; often found incidentally on prenatal karyotype

Question 6

Cri du chat (5p deletion): key features

Answer 6

⭐ High-pitched cat-like cry — laryngeal hypoplasia/dysfunction | ⭐ Microcephaly, hypertelorism, downslanting palpebral fissures, micrognathia | Severe intellectual disability; low birth weight | CHD ~15-20% (VSD, ASD); larger deletion = more severe | 🔑 Cat cry + microcephaly = Cri du chat; most de novo

Question 7

22q11.2 deletion (DiGeorge): CATCH-22 mnemonic

Answer 7

⭐ C — Conotruncal Cardiac defects: TOF (#1), interrupted aortic arch type B, truncus | ⭐ A — Abnormal facies: long face, tubular nose, small ears | ⭐ T — T-cell deficiency (thymic aplasia) -> avoid live vaccines | ⭐ C — Cleft palate / velopharyngeal insufficiency -> hypernasal speech | ⭐ H — Hypocalcemia (hypoparathyroidism) -> neonatal seizures, jitteriness | 🔑 Neonatal hypocalcemia + conotruncal defect -> FISH/microarray; most common microdeletion (~1:4,000)

Question 8

Wolf-Hirschhorn (4p deletion): features

Answer 8

⭐ ‘Greek warrior helmet’ facies: widely spaced eyes, prominent glabella, broad nasal bridge | ⭐ Microcephaly, micrognathia, cleft lip/palate | ⭐ Neonatal-onset seizures; severe intellectual disability | Heart defects (~30-50%), hypospadias, growth retardation | 🔑 Greek helmet face + neonatal seizures + 4p deletion

Question 9

Beckwith-Wiedemann syndrome: features and genetics

Answer 9

⭐ Macrosomia, macroglossia (airway risk), omphalocele/umbilical hernia | ⭐ Ear pits/creases — distinctive and frequently tested | ⭐ Neonatal hypoglycemia due to hyperinsulinism — monitor glucose closely | ⭐ Hemihypertrophy, visceromegaly | ⭐ Tumor risk: Wilms + hepatoblastoma -> abdominal US q3 months until age 8 | 🔑 11p15 imprinting defect; associated with ART/IVF; macroglossia + omphalocele + hypoglycemia = BWS

Question 10

Prader-Willi syndrome: neonatal presentation and genetics

Answer 10

⭐ #1 cause of profound neonatal hypotonia — floppy infant, poor suck -> tube feeds | ⭐ Cryptorchidism (males), almond-shaped eyes, small hands/feet, fair pigmentation | ⭐ Hyperphagia in childhood -> morbid obesity | ⭐ Deletion paternal 15q11-q13 (70%); maternal UPD15 (25%); imprinting defect (5%) | ⭐ Methylation analysis first-line; FISH confirms deletion | 🔑 Floppy baby + cryptorchidism + later obesity = PWS; same region, opposite parent = Angelman

Question 11

Angelman syndrome: features and genetics

Answer 11

⭐ Happy demeanor, frequent unprovoked laughter — ‘happy puppet’ | ⭐ Absent/minimal speech with relatively preserved comprehension | ⭐ Seizures; EEG: high-amplitude delta waves with spike-wave | ⭐ Ataxic jerky gait; microcephaly; hypopigmentation | ⭐ Deletion maternal 15q11-q13 (70%); paternal UPD15; UBE3A mutation | 🔑 Maternal deletion = Angelman; paternal deletion = PWS — same chromosome, opposite parent

Question 12

Silver-Russell syndrome: features and genetics

Answer 12

⭐ Severe symmetric IUGR with relative macrocephaly (small body, big head) | ⭐ Triangular face, prominent forehead, clinodactyly of 5th finger | ⭐ Body asymmetry (hemihypotrophy) | Hypoglycemia from poor intake; feeding difficulties, GER | ⭐ Loss of methylation at H19/IGF2 locus (11p15) ~40%; maternal UPD7 ~10% | 🔑 SGA + relative macrocephaly + asymmetry = SRS; GH therapy used

Question 13

Noonan syndrome: features and genetics

Answer 13

Turner-like + male OR normal karyotype = Noonan; HCM = think RAF1
⭐ Phenocopies Turner but NORMAL karyotype; affects both sexes equally | ⭐ Webbed neck, ptosis, hypertelorism, downslanting palpebral fissures, shield chest | ⭐ Pulmonary stenosis most common CHD (~50%); HCM (~20%) — especially RAF1 mutation | ⭐ Short stature, cryptorchidism, lymphedema, bleeding tendency | PTPN11 (~50%), RAF1, SOS1, KRAS; AD; RAS/MAPK pathway | 🔑 Turner-like + male OR normal karyotype = Noonan; HCM = think RAF1

Question 14

CHARGE syndrome: criteria and genetics

Answer 14

⭐ C — Coloboma; H — Heart defects (conotruncal, ASD, VSD) | ⭐ A — choanal Atresia (bilateral -> fails CPCAP test; respiratory distress) | ⭐ R — Retarded growth; G — Genital abnormalities; E — Ear anomalies/deafness | ⭐ Semicircular canal hypoplasia — near-pathognomonic | CHD7 mutation (~65%); mostly de novo, AD | 🔑 Bilateral choanal atresia + semicircular canal hypoplasia = CHARGE; feeding/aspiration = major neonatal concern

Question 15

VACTERL association: components and key facts

Answer 15

⭐ V — Vertebral; A — Anal atresia; C — Cardiac (VSD most common) | ⭐ TE — Tracheo-Esophageal fistula (Type C = EA + distal TEF most common) | ⭐ R — Renal (agenesis, horseshoe); L — Limb (radial ray defects) | >=3 features for diagnosis; NOT a single-gene disorder | Associated with maternal diabetes, valproate, IUGR | 🔑 EA/TEF + vertebral anomalies -> VACTERL workup; radial ray defects + EA = classic

Question 16

Pierre Robin sequence: features and management

Answer 16

⭐ Sequence: micrognathia -> glossoptosis -> posterior U-shaped cleft palate | ⭐ Airway obstruction — prone positioning first-line; NPA if needed; rarely tracheostomy | Feeding difficulties, FTT, aspiration risk | ⭐ Isolated OR part of: Stickler (most common), 22q11, Treacher Collins — always evaluate | 🔑 U-shaped cleft + micrognathia = Pierre Robin; Stickler = myopia + HL + joint laxity

Question 17

Treacher Collins: features and inheritance

Answer 17

⭐ Bilateral malar + mandibular hypoplasia (fish-like face) | ⭐ Downslanting palpebral fissures, coloboma of lower eyelid, absent lower lid eyelashes medially | ⭐ Bilateral microtia/aural atresia -> conductive HL (no SNHL component) | Cleft palate ~30%; airway may need neonatal tracheostomy | TCOF1; AD with variable expressivity; ~60% de novo | 🔑 NORMAL intelligence + bilateral conductive HL + downslanting fissures = Treacher Collins

Question 18

Alagille syndrome: features and genetics

Answer 18

⭐ Bile duct paucity on liver biopsy -> conjugated hyperbilirubinemia/cholestasis | ⭐ Butterfly vertebrae + posterior embryotoxon (slit lamp) + peripheral pulmonic stenosis | Triangular facies, broad forehead, deep-set eyes, bulbous nose | ⭐ JAG1 (~94%) or NOTCH2; AD with variable expressivity | Progressive liver disease -> transplant in some | 🔑 Conjugated jaundice + butterfly vertebrae + embryotoxon + pulmonic stenosis = Alagille

Question 19

Kabuki syndrome: features and genetics

Answer 19

⭐ Long palpebral fissures with lateral lower lid eversion; arched eyebrows (sparse lateral third) | ⭐ Persistent fetal fingertip pads — highly distinctive | Neonatal hypotonia, feeding difficulties; joint laxity; short stature; intellectual disability | CHD ~30-50%; cleft palate; hearing loss; seizures | KMT2D mutation (~75%); AD, usually de novo | 🔑 Fetal fingertip pads + long palpebral fissures = Kabuki

Question 20

Cornelia de Lange syndrome: features and genetics

Answer 20

* NIPBL (chr 5p13). AR*
⭐ Synophrys + long philtrum + thin upper lip + downturned mouth — classic gestalt | ⭐ Limb defects: small hands -> oligodactyly -> phocomelia (severe end) | ⭐ Severe IUGR, microcephaly, feeding difficulties, GERD | CHD ~25%; cleft palate; hearing loss; self-injurious behavior | NIPBL mutation (~60%); cohesinopathy; AD, usually de novo | 🔑 Synophrys + limb reduction + IUGR = CdLS; upper limb reduction = more severe

Question 21

Achondroplasia: features, genetics, neonatal concerns

Answer 21

⭐ Most common NON-LETHAL skeletal dysplasia | ⭐ Rhizomelic shortening, macrocephaly with frontal bossing, midface hypoplasia, trident hand | ⭐ FGFR3 gain-of-function G380R (~99%); AD; 80% de novo; paternal age effect | ⭐ KEY neonatal risk: foramen magnum stenosis -> central apnea, hypotonia, sudden death -> MRI | Normal intelligence; hydrocephalus and spinal stenosis surveillance | 🔑 Rhizomelia + trident hand + frontal bossing; G380R = most common point mutation in any AD disorder

Question 22

Osteogenesis imperfecta: types and neonatal features

Answer 22

⭐ Type I (mild): blue sclerae, fractures with minimal trauma, normal stature, conductive HL | ⭐ Type II (lethal perinatal): multiple fractures at birth, beaded ribs — death in neonatal period | Type III: fractures at birth, white/gray sclerae, progressive deformities — most severe surviving type | Type IV: white sclerae, variable fractures, dentinogenesis imperfecta | ⭐ Wormian bones on skull X-ray; COL1A1/COL1A2 (AD); bisphosphonates for Tx | 🔑 Fractures + blue sclerae + wormian bones = OI; blue sclerae most prominent in Type I

Question 23

Thanatophoric dysplasia: features and significance

Answer 23

⭐ Most common LETHAL skeletal dysplasia | ⭐ Extremely short limbs, very narrow thorax -> pulmonary hypoplasia -> respiratory failure | ⭐ Type I: curved ‘telephone receiver’ femurs; Type II: straight femurs + severe cloverleaf skull | FGFR3 gain-of-function (R248C, Y373C); de novo AD | Usually lethal in neonatal period | 🔑 Telephone receiver femurs = TD Type I; FGFR3 spectrum: TD (lethal) -> achondroplasia (non-lethal)

Question 24

PKU (phenylketonuria): genetics and neonatal management

Answer 24

⭐ PAH gene; AR; phenylalanine hydroxylase deficiency -> Phe accumulates | ⭐ NBS: elevated Phe (>360 umol/L classic PKU); start low-Phe diet ASAP | ⭐ Untreated: intellectual disability, seizures, mousy/musty odor, fair skin/hair/eyes | ⭐ Maternal PKU: elevated maternal Phe -> embryopathy (microcephaly, CHD, IUGR) even in heterozygous fetus | Sapropterin (BH4) responsive in ~25-50% of PAH mutations | 🔑 Musty odor + fair pigmentation + intellectual disability = untreated PKU; maternal PKU = teratogen

Question 25

MSUD (maple syrup urine disease): genetics and presentation

Answer 25

⭐ BCKDHA/B or DBT mutations; AR; branched-chain alpha-keto acid dehydrogenase deficiency | ⭐ Accumulation of leucine (most toxic), isoleucine, valine + keto acids | ⭐ Maple syrup/burnt sugar odor in urine AND cerumen (earwax) — pathognomonic | ⭐ Encephalopathy onset day 3-5: poor feeding -> lethargy -> opisthotonos -> cerebral edema | Tx: high-calorie glucose/lipid infusion; dialysis for severe hyperleucenemia; BCAA-free formula | 🔑 Maple syrup cerumen + encephalopathy day 3-5; leucine most neurotoxic; liver transplant curative

Question 26

Galactosemia (classic): genetics and neonatal presentation

Answer 26

⭐ GALT gene; AR; galactose-1-phosphate uridylyltransferase deficiency | ⭐ After first breast/formula feeds: conjugated jaundice, hepatomegaly, coagulopathy | ⭐ E. coli neonatal sepsis in a jaundiced infant -> think galactosemia | ⭐ Oil-droplet nuclear cataracts; hypoglycemia | ⭐ NBS positive; stop lactose/galactose -> soy formula immediately | 🔑 E. coli sepsis + jaundice + cataracts = galactosemia; even treated: cognitive delay + premature ovarian insufficiency

Question 27

MCAD deficiency: genetics and clinical significance

Answer 27

⭐ ACADM gene; AR; MOST COMMON fatty acid oxidation disorder | ⭐ Cannot oxidize medium-chain fatty acids during fasting -> energy crisis | ⭐ Hypoketotic hypoglycemia — KEY: inappropriately low ketones for degree of hypoglycemia | ⭐ C8 (octanoylcarnitine) elevated on NBS — diagnostic marker | Presentation: encephalopathy, seizures, sudden death; historically misdiagnosed as SIDS | 🔑 Hypoketotic hypoglycemia + fasting illness + elevated C8 = MCAD; prior 'SIDS' sibling

Question 28

Propionic and methylmalonic acidemia

Answer 28

***Anion gap acidosis + hyperammonemia + ketonuria in neonate = organic acidemia; PA -> cardiomyopathy; MMA -> nephropathy*** ⭐ Propionic acidemia (PA): PCCA/PCCB gene; propionyl-CoA carboxylase deficiency | ⭐ MMA: MUT gene (or cbl groups); methylmalonyl-CoA mutase deficiency | ⭐ Both: neonatal encephalopathy, anion gap metabolic acidosis, hyperammonemia, ketonuria | ⭐ PA-specific: neutropenia/thrombocytopenia + dilated cardiomyopathy (late — board favorite) | ⭐ MMA-specific: tubulointerstitial nephritis -> CKD; metabolic stroke of basal ganglia | 🔑 Anion gap acidosis + hyperammonemia + ketonuria in neonate = organic acidemia; PA -> cardiomyopathy; MMA -> nephropathy

Question 29

Isovaleric acidemia and glutaric aciduria type 1

Answer 29

⭐ Isovaleric acidemia (IVD gene): 'sweaty feet' odor — isovaleric acid (leucine catabolism) | Neonatal crisis: acidosis, encephalopathy, bone marrow suppression | Tx: leucine restriction + glycine + carnitine | ⭐ Glutaric aciduria type 1 (GCDH gene): macrocephaly at birth; striatal injury with fever -> dystonia | ⭐ GA1 can mimic non-accidental trauma: subdural hematoma + retinal hemorrhage + macrocephaly | 🔑 Sweaty feet = IVA; macrocephaly + 'subdural' + dystonia = GA1 (not always abuse)

Question 30

Urea cycle defects: presentation and key entities

Answer 30

⭐ Day 1-5: hyperammonemia, encephalopathy, respiratory alkalosis (early sign) | ⭐ OTC deficiency: most common UCD; X-LINKED recessive — only UCD that is X-linked | ⭐ OTC vs CPS1: both have low citrulline; OTC has elevated urine orotate; CPS1 does not | ⭐ Citrullinemia (ASS1): very high citrulline on plasma amino acids | Argininosuccinic aciduria (ASL): trichorrhexis nodosa later | Tx: stop protein; IV glucose; nitrogen scavengers; dialysis if NH3 >500 | 🔑 NH3 >150 umol/L in neonate = UCD until proven otherwise; urine orotate distinguishes OTC from CPS1

Question 31

Fatty acid oxidation: VLCAD and LCHAD

Answer 31

⭐ VLCAD (ACADVL): C14:1 acylcarnitine elevated on NBS; hypoketotic hypoglycemia + cardiomyopathy | ⭐ LCHAD (HADHA): C16-OH acylcarnitine elevated; hypoketotic hypoglycemia + cardiomyopathy + rhabdomyolysis | ⭐ LCHAD-specific: pigmentary retinopathy + peripheral neuropathy — unique among FAO disorders | ⭐ MATERNAL LCHAD: LCHAD-affected fetus causes AFLP/HELLP in heterozygous carrier mother | Tx: avoid fasting; MCT oil; uncooked cornstarch | 🔑 AFLP/HELLP in mother -> baby has LCHAD; retinopathy in FAO disorder = LCHAD only

Question 32

Pompe disease (GSD II): neonatal features

Answer 32

*** Floppy baby + HCM + macroglossia + giant ECG voltages = infantile Pompe; ERT (alpha-glucosiderase) is life-saving*** ⭐ GAA gene; AR; lysosomal acid alpha-glucosidase deficiency -> glycogen in lysosomes | ⭐ Classic infantile: hypertrophic cardiomyopathy + hypotonia + macroglossia in first weeks | ⭐ ECG: massive QRS voltage + short PR interval — nearly pathognomonic | ⭐ NBS: acid alpha-glucosidase enzyme activity; Tx: ERT (alglucosidase alfa) — dramatically improves survival | Without treatment: death by 1-2 years from cardiorespiratory failure | 🔑 Floppy baby + HCM + macroglossia + giant ECG voltages = infantile Pompe; ERT (alpha-glucosiderase) is life-saving

Question 33

Lysosomal storage diseases with neonatal presentation

Answer 33

***tay-sachs, niemann-pick, GM1 gangliosidosis, gaucher*** ⭐ Cherry-red macula DDx: Tay-Sachs (HEXA), Niemann-Pick A (SMPD1) (of note, type C is most common and does not have cherry red spot), GM1 gangliosidosis (GLB1), Sandhoff | ⭐ Niemann-Pick type A: hepatosplenomegaly + hypotonia + cherry-red spot; rapidly progressive | ⭐ GM1 gangliosidosis: coarse facies + hepatosplenomegaly + cherry-red spot + dysostosis multiplex | ⭐ Gaucher type 2: hepatosplenomegaly + opisthotonus + ichthyosis; GBA gene; rapidly fatal | Hydrops fetalis with severe forms (Gaucher, GM1, MPS VII) | 🔑 Cherry-red macula + neuro regression = LSD; coarse facies + hepatosplenomegaly + dysostosis = MPS or GM1

Question 34

Biotinidase deficiency: features and treatment

Answer 34

⭐ BTD gene; AR; inability to recycle biotin -> multiple carboxylase deficiency | ⭐ Classic tetrad: seizures + hypotonia + alopecia + periorificial rash | Organic aciduria, lactic acidosis, hearing loss, optic atrophy if untreated | ⭐ NBS: biotinidase enzyme activity; Tx: oral biotin — completely preventable and reversible | Holocarboxylase synthetase deficiency: similar but earlier/neonatal onset; also biotin-responsive | 🔑 Seizures + alopecia + rash + organic aciduria = biotinidase deficiency; biotin is curative — do NOT miss

Question 35

Peroxisomal disorders: Zellweger spectrum

Answer 35

* Profound hypotonia + seizures day 1 + stippled epiphyses + elevated VLCFA = Zellweger* ⭐ PEX gene mutations; complete absence of functional peroxisomes | ⭐ Neonatal: profound hypotonia, seizures (day 1), high forehead, flat facies, large fontanelles | ⭐ Stippled epiphyses on X-ray — key radiographic finding | ⭐ Hepatomegaly, renal cortical cysts on US, cholestasis | ⭐ Elevated VLCFA in plasma — screening test | 🔑 Profound hypotonia + seizures day 1 + stippled epiphyses + elevated VLCFA = Zellweger

Question 36

Mitochondrial disease: neonatal presentations

Answer 36

⭐ Lactic acidosis + encephalopathy + multi-organ involvement = mito until proven otherwise | ⭐ Leigh syndrome: symmetric T2 hyperintensity in basal ganglia/brainstem on MRI | ⭐ Elevated plasma lactate; L:P ratio >20 suggests ETC defect | ⭐ Maternal inheritance for mtDNA mutations; AR for nuclear-encoded ETC subunits | Pearson syndrome: sideroblastic anemia + exocrine pancreatic dysfunction; large mtDNA deletion | 🔑 'Everything elevated' (lactate, ammonia, organic acids) = mito; Leigh = basal ganglia lesions on MRI

Question 37

Congenital hypothyroidism: genetics and NBS protocol

Answer 37

⭐ Most common cause: thyroid dysgenesis (agenesis/ectopic) — usually sporadic | ⭐ Dyshormonogenesis (AR): TPO, TG, DUOX2 mutations -> goiter; 25% recurrence risk | ⭐ NBS: elevated TSH; screen at 24-48h (repeat if <24h or premature) | ⭐ Untreated: prolonged jaundice, large fontanelles, umbilical hernia, macroglossia, constipation, hoarse cry | ⭐ Start levothyroxine ASAP; normalize T4 within 2 weeks, TSH within 1 month | 🔑 Prolonged jaundice + umbilical hernia + macroglossia + hoarse cry = hypothyroidism; every day of delay = IQ points lost

Question 38

Congenital adrenal hyperplasia (21-hydroxylase): neonatal management

Answer 38

⭐ CYP21A2 gene; AR; >90% of CAH; elevated 17-OHP on NBS | ⭐ Classic salt-wasting (75%): adrenal crisis at 1-3 weeks — hyponatremia, hyperkalemia, hypoglycemia, shock | ⭐ 46,XX females: virilization -> ambiguous genitalia; males appear normal at birth | ⭐ Dx: elevated 17-OHP; low Na, high K, low cortisol, high ACTH, elevated androgens | ⭐ Tx: hydrocortisone + fludrocortisone + NaCl supplementation in infants | 🔑 Male neonate + vomiting + hyponatremia + hyperkalemia at 2 weeks = CAH salt-wasting crisis

Question 39

Congenital CMV: features, diagnosis, and treatment

Answer 39

⭐ Most common congenital infection (~1% live births); 90% asymptomatic at birth | ⭐ Symptomatic: SGA, petechiae/purpura, hepatosplenomegaly, jaundice, thrombocytopenia | ⭐ Periventricular calcifications — key finding (vs. toxo: diffuse/scattered) | ⭐ SNHL — most important sequela; occurs in BOTH symptomatic and asymptomatic CMV | ⭐ Dx: CMV PCR from urine or saliva within first 3 weeks | ⭐ Tx: valganciclovir x 6 months for symptomatic CNS disease | 🔑 Periventricular calcifications + SNHL = CMV; progressive HL even in asymptomatic infants

Question 40

Congenital rubella: classic triad and features

Answer 40

⭐ Classic triad: bilateral nuclear cataracts + sensorineural deafness + CHD (PDA, peripheral pulmonic stenosis) | ⭐ Blueberry muffin rash (dermal extramedullary hematopoiesis) | Hepatosplenomegaly, thrombocytopenic purpura, microcephaly, glaucoma, salt-and-pepper retinopathy | ⭐ 1st trimester risk >80%; 2nd trimester: mainly deafness/retinopathy; >20 wks: rare | Virus shed up to 1 year — contact precautions | 🔑 Cataracts + CHD + deafness = rubella triad; prevention = MMR vaccine

Question 41

Congenital toxoplasmosis: classic triad and features

Answer 41

⭐ Classic triad: chorioretinitis + hydrocephalus + diffuse/scattered intracranial calcifications | ⭐ Scattered calcifications throughout brain — vs. CMV periventricular only | ~70-90% asymptomatic at birth; sequelae develop months to years later | ⭐ Chorioretinitis = most common sequela; bilateral, recurrent | ⭐ Dx: Toxoplasma IgM/IgA in newborn; CSF PCR; ophthalmology; head CT | 🔑 Scattered calcifications + hydrocephalus = toxo; maternal risk = cat litter + raw meat; Tx: pyrimethamine + sulfadiazine + folinic acid x 1 year

Question 42

Congenital syphilis: early vs. late features and treatment

Answer 42

⭐ Early (<2 yr): snuffles (bloody/purulent rhinorrhea) — #1 early sign; maculopapular rash on palms and soles | ⭐ Hepatosplenomegaly, jaundice; osteochondritis -> 'celery stalk' metaphyses on X-ray | ⭐ Pseudoparalysis of Parrot: infant avoids moving limb due to bone pain | ⭐ Late (>2 yr): Hutchinson triad = Hutchinson teeth + interstitial keratitis + CN VIII deafness | Dx: VDRL/RPR + FTA-ABS; long bone X-ray; LP; CBC | 🔑 Snuffles + palms/soles rash + celery stalk bones = early; Hutchinson triad = late; Tx: IV penicillin G x 10 days

Question 43

Congenital Zika: features and diagnosis

Answer 43

*Microcephaly + redundant scalp folds + cortical malformations* ⭐ Severe microcephaly with craniofacial disproportion + redundant scalp skin folds | ⭐ Cortical malformations: lissencephaly, pachygyria, polymicrogyria; ventriculomegaly; cortical calcifications | Arthrogryposis, hypertonia/hypotonia, club foot | ⭐ Ophthalmologic: macular/retinal lesions, optic nerve hypoplasia, coloboma | SNHL, seizures, profound neurodevelopmental disability | 🔑 Microcephaly + redundant scalp folds + cortical malformations = Zika; no treatment; prevention = mosquito avoidance