Peds Final Study Guide

What are the phenotypic features of T21?

Hypotonia (often the first newborn clue)

Brachycephaly, flat occiput, flat nasal bridge, upslanting palpebral fissures, epicanthal folds, protruding tongue, midface hypoplasia

Single transverse palmar crease, sandal gap between 1st and 2nd toe

What is in the inheritance pattern/gene difference of T21?

Most common chromosomal aneuploidy in liveborns

95% nondisjunction (usually maternal meiosis I; risk increases with maternal age)

3% Robertsonian translocation

2% Mosaicism

Why would you karyotype parents of a child with T21?

Translocation down syndrome, as the risk of recurrence is higher.

What are the associated conditions with T21?

CHD (AV canal defect is classic!)

GI duodenal atresia

Congenital and acquired hypothyroidism

10x-20x increased leukemia risk

Atlantoaxial instability

What are the phenotypic features of T18 (Edwards Syndrome)?

Clenched fist with overlapping fingers

Rocker-bottom feet, hypoplastic nails

Prominent occiput, micrognathia, low-set malformed ears, short sternum

Poor prognosis, about 13% survive past 1 year.

What is the inheritance pattern/gene difference of T18?

Second most common autosomal trisomy, not inherited just a random mutation. 47, XX,+18 or 47, XY, +18

What are the phenotypic features of Klinefelter?

Prepubertal boys look normal

Teens/adult are tall with long limbs, small firm (infantile-like) tests, gynecomastia

Hypergonadotropic hypogonadism, azoospermia.

No facial hair, deep voice, lack of libido.

Osteopenia and osteoporosis in adults.

Most are infertile.

What is the genetic inheritance/pattern of Klinefelters?

Presence of an extra X chromosome (47, XXY)

What are the phenotypic features of Turner syndrome?

Relatively mild, typical intelligence, normal life expectancy.

Short stature, webbed neck, low-set ears, shield-shaped chest with widely spaced nipples, puffy hands/feet (infancy)

Cardiac defects in 45% (bicuspid aortic valve and CoA)

Horseshoe kidney and other renal anomalies

Streak ovaries, estrogen deficiency, delayed/incomplete puberty and primary amenorrhea.

What is the inheritance pattern/gene affected in Turner syndrome?

Single sex chromosome loss: 45, X

Can also have mosaic or structural X abnormalities/partial deletion.

Estimated 90% of 45, X embryos result in spontaneous miscarriage.

What are the phenotypic features of achondroplasia?

Disproportionate short stature with rhizomelic limb shortening

Macrocephaly with frontal bossing, flat midface

Trident hands, lumbar lordosis, bowing of legs

Foramen magnum stenosis (hydrocephalus, central apnea)

Later on in life: middle-ear disease/hearing loss, spinal stenosis/sciatica in adults

Normal intelligence and normal lifespan

What is the inheritance pattern/gene affected in achondroplasia?

Autosomal dominant, pathogenic variant in gene FGFR3 (fibroblast growth factor receptor type 3)

Defect in cartilage-derived bone.

80% are de novo variants (linked to advanced paternal age)

What are the phenotypic features of osteogenesis imperfecta (Brittle bone disease)?

Bone fragility - fractures with minimal trauma, low bone density

Blue sclerae

Dentinogenesis imperfecta (weak, discolored teeth)

Early conductive/sensorineural hearing loss

Short stature, wormian skull bones, scoliosis, joint hypermobility, bowed legs or arms, easy bruising

What are the different types of OI?

Type 1: most mild and most common, normal height

Type 2: lethal in utero, after birth

Type 3/4: moderate/severe deformities, short stature, mobility aids needed.

What is the treatment for OI?

Bisphosphonates

What is the inheritance pattern/gene affected in OI?

Usually autosomal dominant; many are de novo.

Mutation is COL1A1 and COL1A2, makes type 1 collagen that gives bones strength/flexibility.

What are the phenotypic features of fragile X?

Most common inherited cause of intellectual disability

Long face, large/prominent ears, prominent jaw and forehead

Macroorchidism (large tests)

Intellectual disability (mild to profound, ASD features, hyperactivity)

Connective tissue issues, joint laxity, mitral valve prolapse

Premutation carriers are typically normal but can have premature ovarian insufficiency (females) or fragile X tremor/ataxia syndrome (older males)

What is the inheritance pattern/gene affected in Fragile X?

X-linked dominant mutation in gene FMR1 with CGG trinucleotide repeat expansion, >50% of DNA has repeat sequences of 2-3 bases; normal: 0-45 repeats, full mutation >200 repeats.

When would you order karyotype testing?

To count or structure the whole chromosome (aneuploidys or translocations)

When would you order chromosomal microarray (array CGH)?

First-line for multiple anomalies/unexplained ID; detects copy-number changes

Has largely replaced routine karyotype for anomalies without a specific suspected syndrome.

When would you order FISH?

To confirm a specific deletion or rearrangement.

When would you order DNA sequencing?

To see a single gene, panel, exome (ES) or whole genome (WGS)

When would you order trinucleotide repeat testing?

For Fragile X, Huntington, etc.

What are the red flag symptoms of inborn errors of metabolism?

Developmental regression after normal development

Recurrent vomiting/dehydration/encephalopathy/lethargy/abnormal tone, esp. after illness, feeding or fasting.

Metabolic acidosis, hypoglycemia, hyperammonemia

Abnormal body/urine odor

Multisystem involvement, family history, consanguinity.

What is the symptomati child triad with inborn errors of metabolism?

Plasma amino acids, plasma acylcarnitine profile, urine organic acids (+ ammonia, glucose, gases, lactate)

What is the inheritance pattern/gene affected in PKU?

Autosomal recessive amino acid disorder

Phenylalanine hydroxylase (PAH) deficiency causes phenylalanine to not be able to covert to tyrosine.

What is the clinical presentation of PKU?

Baby eats protein, phenylalanine accumulates, and it is toxic to the developing brain.

If untreated, results in progressive intellectual disability, microcephaly, seizures, eczema, "musty/mousy" odor of breath/skin/urine, hypopigmentation.

How do you manage PKU?

Lifelong phenylalanine restricted diet + phenylalanine free medical formula/medical foods.

Still must have minimal phenylalanine in diet to maintain normal development.

Goal is to have blood phenylalanine levels maintained between 120-360 mM.

Tyrosine becomes essential for supplementation.

What is the treatment option for teens/adults?

Pegvaliase, daily injectable enzyme replacement therapy. Helps maintain reduced phenylalanine, often allows for normal diet.

What is the management for maternal PKU?

Strict control before/during pregnancy or the fetus develops microcephaly, brain injury and cardiac defects (teratogenic defect)

What is the inheritance pattern/gene affected in galactosemia?

Autosomal recessive inherited disease

Inability to metabolize galactose due to deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme which causes an accumulation of galactose-1-phosphate.

What is the clinical presentation of classic galactosemia?

Neonate consumes lactose (breast milk or cows milk formula) and can lead to liver failure.

S/sx: hepatomegaly, hyperbilirubinemia, coag disorders, hypoglycemia. Vomiting, diarrhea, poor feeding. Cataracts, neonatal seizures, lethargy/irritable.

How do you confirm galactosemia?

RBC GALT enzyme assay. But don't wait for results if suspicious, remove exposure ASAP!

What is the treatment for classic galactosemia?

Lethal if not treated within 1 week of life.

Immediately remove lactose/galactose from the diet, stop breast milk and standard cow-milk formula; use an appropriate lactose free formula and metabolic follow up.

What is congenital hypothyroidism?

Single most preventable cause of intellectual disability

T4, T3 and TSH don't cross placenta significantly (trickle effect): fetal serum reflects fetal secretion and metabolism. Maternal thyroid antibodies, iodides and hyperthyroid meds for mom cross placenta and affect fetal thyroid function.

What is the clinical presentation of congenital hypothyroidism?

Usually asymptomatic at birth, because mom's thyroid hormone protects them in utero (which is why we screen instead of waiting for sx)

Late signs if missed:

Prolonged jaundice

Large posterior fontanelle

Macroglossia

Umbilical hernia

Constipation

Lethargy

Hypothermia

Poor feeding

Hoarse cry

Later: growth failure, developmental delay

Describe the newborn screen for congenital hypothyroidism

NBS at 24-72 hours of life crucial to make early dx and start treatment

What is the initial management of congenital hypothyroidism?

Levothyroxine start newborn at 10-15 mcg/kg/day.

Dose changes with age and titrated over time to maintain TSH and T4 in normal range. Monitor TFTs frequently for life.

If there is markedly elevated TSH on NB screen, start levo after drawing confirmatory sample (don't wait for results)

If untreated there is irreversible neurocognitive damage, if treated early there are normal outcomes.

What defines short stature?

Height >2 SD below mean for age/sex. Majority of short children have 1 of 3 benign variants: familial short stature, constitutional delay or idiopathic. Only 5% have true pathology.

Describe familial short stature

Height: short (matches family)

Growth velocity: normal

Bone age: normal (=chronological age)

Puberty: normal timing

Family hx: short parents

Final adult age: short (as expected)

Describe constitutional delay

Height: short for age

Growth velocity: normal (slow tempo)

Bone age: delayed (=height age)

Puberty: delayed

Family hx: "late bloomers"

Final adult age: normal (catch-up)

Describe GH deficiency

Height: short, often severe

Growth velocity: decreased

Bone age: delayed

Puberty: normal/delayed

Family hx: usually none

Final adult age: short if untreated.

What are the screening tests for GH status?

IGF-1/IGF-BP3

What is the treatment for GH deficiency?

Recombinant human GH

What are the diagnostic criteria for DM in kids?

Any one of (confirm if asymptomatic):

Fasting glucose ≥126

Random glucose ≥200

2-hr OGTT ≥200

HbA1c ≥6.5

What is the pre-DM criteria in kids?

Fasting 100-125

2hr GTT: 140-199

What is the classic T1D presentation?

Lean child, acute polyuria/polydipsia/polyphagia + weight loss, may present in DKA. Autoantibodies to islet cell antigens are present. Weaker family hx.

What is the mechanism of T1D?

Autoimmune B-cell (islet) destruction

What is the classic T2D presentation?

Obese teen, acanthosis nigricans, strong family hx, metabolic syndrome.

What is the mechanism of T2D?

Insulin resistance + relative deficiency.

What should you check if you're unsure if a child is a type 1 or type 2 diabetic/

Check autoantibodies (T1D) and C peptide (T2)

What is the clinical triad of DKA?

1. Hyperglycemia (BG >200)

2. Ketones in blood or urine

3. Metabolic acidosis: venous pH

What is the presentation of a child in DKA?

Polyuria/polydipsia, N/V, abdominal pain, Kussmaul respirations, fruity breath, dehydration, AMS.

What are the treatment pillars of DKA?

Fluids first, then insulin infusion, correct electrolytes (watch K), monitor closely.

What is the most feared complication of DKA?

Cerebral edema.

How do you manage T1D?

Lifelong insulin. Basal-bolus regimen, with long-acting basal at bedtime and rapid-acting bolus with meals. Use an insulin pump if possible.

A1c goal

How do you manage T2D?

Lifestyle modification for all.

Metformin first line PO

GLP-1 approved in kids ≥10

If these fail, add insulin.

What are the risks of Vitamin D deficiency in kids?

Development of Rickets (decreased bone mineralization)

Bones become soft and metaphysis of long bones widen at growth plate

Poor linear growth

Bowing of legs on weight bearing

Frontal bossing

Softening of skull (ping-pong effect, craniotabes)

Risk of hypocalcemic seizures/tetany

Who is at the biggest risk of developing Rickets?

Exclusively breastfed babies

Born to Vitamin-D deficient mothers

Poor direct sun exposure

What is the treatment for vitamin D deficiency and Rickets?

Replace vitamin D and calcium

Nutritional Rickets: may give single large weekly vitamin D dose or multiple smaller replacement doses

F/u labs and x-rays (Rickets should heal if treated early)

Surgery may be required to straighten legs.