Ch 10: Diseases of Childhood/infancy Flashcards
What happens with exposure to cyclopamine?
Inhibits Hedgehog signaling
Leads to:
Holoproencephaly
Cyclopia
What happens with exposure to Valproic acid?
Reduced expression of HOX proteins, which are important for patterning of limbs, vertebrae, and craniofacial structures
Leads to: Limb mutations (similar to thalidomide)
What happens with exposure to Vitamin A deficiency?
All-trans retinoic acid is key for normal development
Leads to:
Eyes, GU, CV, diaphragm, lung probs
What happens with exposure to Vitamin A toxicity?
Too much inhibits TGF-B, important for palatogenesis
Leads to:
CNS and cardiac defects
Craniofacial defects = cleft lip/palate
How would you classify preterm?
Anytime before 37 weeks of gestation
What are the risk factors associated with preterm premature rupture of membranes?
Prior history of PPROM
Vaginal bleeding
Maternal smoking
Low SE status and poor maternal nutrition
What is the MOD behind PPROM?
Infectious agents activated TLR –> deregulate prostaglandin expression –> uterine smooth muscle contraction
What are some common infections seen with PPROM?
Ureaplasma urealyticum mycoplasma hominis Gardnerella vaginalis Trichomonas Gonorrhea Chlamydia
What can result with PPROM?
Gives rise to RDS, necrotizing enterocolitis, sepsis, intraventricular and germinal matrix hemorrhage
What gives rise to fetal infections and what sx do you see?
TRCH: Toxoplasmosis Rubella Cytomegalovirus Herpes virus
SX:
fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, vesicular or hemorrhagic skin lesions
What is neonatal RDS? What is the mechanism behind it?
It is a hyaline membrane disease
Commonly associated with preterm males, maternal diabetes, and C-section delivery
There is a lack of surfactant (SP-B and SP-C) production from type 2 pneumocytes, which is accelerated at week 35 of gestation
Lungs will collapse with each successive breath. compounded by soft thoracic wall that get pulled in as diaphragm recedes
What would you see in imaging with RDS?
CXR shows ground-glass infiltrates
What would you see on physical examination of lungs with RDS?
Collapsed alveoli
Necrotic cellular debris on autopsy that is incorporated with eosinophilic hyaline membranes lining bronchioles and alveoli
What are some immediate complications with RDS? What is the mechanism behind them?
Retrolental fibroplasia = retinopathy of maturity, VEGF level low then increase, which causes retinal vessel proliferation –> lesions
Bronchopulmonary dysplasia = inflammatory cytokines IL-1, TNF, IL-6, IL-8 may play a role
What are some long term complications with RDS?
Patent ductus arterioles
Intraventricular hemorrhage
Necrotizing enterocolitis
In who do you see necrotizing enterocolitis most commonly?
Pre mature infants (1 in 10 for very low birth weight)
How is necrotizing enterocolitis triggered?
It is multifactorial
Likely triggered by eating
No single bacterial pathogen has been linked
What is the mechanism behind necrotizing enterocolitis?
PAF (platelet activating factor) –> increases mucosal permeability by promoting enterocyte apoptosis and reducing intercellular tight junctions
What problems does necrotizing enterocolitis lead to in the GI tract?
Target terminal ileum, cecum, and right colon
Leads to distention
Mucosal or transmural coagulative necrosis, ulceration, bacterial colonization and submucosal gas bubbles
Often leas to strictures from fibrosis involved in healing process
How is necrotizing enterocolitis managed?
Most managed conservatively, some need bowel resection
What happens with exposure to Parovirus B19?
Common cause of transplacental infections
Commonly targets erythroid cells
Leads to: erythema infectious (face-slap rash)
What happens with exposure to Group B streptococcus?
Most common cause of early-onset perinatal sepsis and meningitis (within first 7 days of life)
What happens with exposure to Listeria and candida?
Most common cause of late-onset sepsis (7 days to 3 month)
What is immune hydros caused by?
Caused by blood cell antigen incompatibility b/w mother and fetus
B/w Rh- and Rh+ father –> first pregnancy leads to IgM antibodies against Rh+ –> repeat exposure leads to IgG ab that can cross placenta and attach fetus
What are Sx of immune hydrops?
Hemolysis –> anemia –> hypoxic injury to liver –> reduced plasma oncotic pressure –> generalized edema and anasarca (generalized body swelling)
What are the major causes of non-immune hydrops?
1) Cardiovascular
2) Chromosomal anomalies = most common is Turner syndrome (cystic hygroma)
3) Fetal anemia (not Rh- or ABO associated) = usually caused by Parovirus B19, which targets erythroid precursors and causes apoptosis of RBC
What are Sx of non-immune hydrops?
Fetal anemia –> fetal and placenta pale
Liver and spleen enlarged from cardiac failure
Bone marrow = compensatory hyperplasia –> increase hematopoietic activity causes large amounts of immature cells in circulation (erythroblastosis fetalis)
What is PKU? Who is it seen in? What is it caused by?
Common PKU = seen in Scandinavian patients
Caused by autosomal recessive defect in phenylalanine hydroxylase –> unable to convert Phe to Tyr
Try gets shunted into minor pathways (metabolites = toxic) –> abnormal smell
What Sx do you see with PKU and how do you treat it?
Musty odor to body/urine
Severe mental retardation
Decreased pigmentation of hair and skin, eczema
TX = limit Phe in diet (non effective in its with BH4 deficiency)
What is Galactosemia?
Most commonly occurs due to defect in galactose-1-phosphate uridyl transferase (GALT)
Galactose1P accumulates in liver, spleen, lens, kidney, heat, cerebral cortex, erythrocytes
Causes activation of separate pathways –> produces galactitol and galactonate
What Sx do you see with galactosemia?
Jaundice, failure to thrive
Hepatomegaly, widespread scarring similar to cirrhosis
Opacification of lens = cataracts
Mental retardation, alteration in nerve cells (particularly in dentate nuclei of cerebellum)
Amino acuduria
Prone to Ecoli septicemia
Hemolysis and coagulopathy
What is cystic fibrosis? What is its genetic association?
Abnormal Cl- channel, results in highly viscous secretions in lungs that can obstruct airway
1/2500 births - most commonly in caucasians
3 BP deletion, F508 on CTFR
Autosomal recessive
Found on 7q31.2
What Sx do you see in cystic fibrosis?
Influenza
Pseudomonas aeruginosa infections (neutrophils!)
Bronchiectasis and atelectasis
Meconium ileus + rectal prolapse
Hepatic steatosis, focal biliary cirrhosis
Recurrent pancreatitis
Male infertility
What is sudden infant death syndrome (SIDS)?
Sudden death of infant <1 yr old which remains unexplained after thorough investigation
Delayed development in arousal and cardiorespiratory control
Skin = petechiae
What are the risk factors for SIDS?
Vulnerable infant –> maternal smoking, sleeping with parents, overly soft surfaces and thermal stress
Critical development period in homeostatic control
Exogenous stressor
SIDS is a disease of exclusion. What do you need to rule out?
Trauma
What is the most common tumor of infancy? What Sx do you see?
Hemangioma - resolves with age
Skin = flat, large lesions refereed to as port wine stains
Can be associated with von Hippel-Lindau disease
What is a lymphangioma?
Hamartomatous or neoplastic
Usually in neck, axilla, mediastinum and retroperitoneal tissue
What is lymphangiectasis?
Abnormal dilations of preexisting lymph channels
Usually present as diffuse swelling of part or all of extremity
What is the MOD behind congenital infantile fibrosarcoma? What is the prognosis?
Commonly due to 12: 15 translocation
Forms ETV6-NTRK3 fusion –> constitutively active –> excess RAS and PI3K/AKt signaling
Good prognosis
Describe immature vs. mature teratomas.
Immature = malignant teratoma mixed with another germ cell tumor; potential for malignancy depends of amount of immature tissue present
Mature = benign, well-differentiated cystic lesions
What are sacrococcygeal teratomas?
Most common type of teratoma
More so in girl
Seen in coordination with other midline defects = meningocele, spina bifida
What is a neuroblastoma?
Differentiation of primitive neuroblasts into mature elements. Can be small in situ lesions or overt tumors
Describe the inheritance pattern of neuroblastomas.
Usually sporadic
1-2% are familial
Familial often include germline mutation in ALK gene
What is the histology of a neuroblastoma?
Small cells with dark nuclei, cytoplasm and poorly difined borders
Homer-Wright pseudo rosettes = tumors with neutrophils around them
Can stain for enolase and catecholamine-containing granules
What does the presence of Schwann cells indicate in a neuroblastoma?
It is more of a mature ganglioneuroma
Associated with more favorable outcome
In who mostly are neuroblastoma present?
Children under the age of 2 with large and masses, fever, and weight loss
How can you diagnose a neuroblastoma?
90% produce catecholamines –> elevated levels of catecholamines in the blood + VMA and HVA
What skin sx do you see with a neuroblastoma?
Disseminated neuroblastomas with multiple mets can cause deep blue discoloration of skin = blueberry muffin babies
What are the important prognosis factors of neuroblastomas?
1) Age + stage = above 10 mo. gives worse prognosis
2) Morphology
3) Amplification of MYCN = bad –> associated with deletion on chromosome 1
4) Ploidy = hyper diploid –> better prognosis
5) Expression of neurotrophin receptor
What is a Wilms tumor?
Most common primary renal tumor and 4th most common pediatric malignancy in US
Can be bilateral (synchronous) or unilateral (metachronous)
B/l presents 10 mo earlier and usually has germline mutation
What Sx are associated with Wilms tumor?
Will present with large abd masses, HTN, hematuria, fever
What molecule plays are role in Wilms tumor production?
Beta cadherin
Where is metastasis common with Wilms tumor?
Lung
The risk of Wilms tumor is increased with a least 3 recognizable groups of congenital malformations associated with distinct chromosomal loci. What are then?
1) WAGR/WAGI syndrome
2) Denys-Drash syndrome
3) Bekwith-Wiedeman syndrome
Describe WAGR/WAGI syndrome.
33% risk - Germline deletion of 11p13
WAGR = Wilms, Anirdia, Genital anomalies, mental retardation
Result in mutations in:
WT1 = Wilms tumor associated gene
PAX6 = provides instructions for making protein that is involved in early development of eyes, spinal cord, and pancreas
Describe Denys-Drash syndrome.
90% risk
Gonadal dysgenesis (male pseudohermaphrodism) Early onset nephropathy --> renal failure Increase risk of gonadoblastoma
Describe Beckwith-Weidemann syndrome.
Example of genomic imprinting - 11p15.5 (WT2-IGF2)
Some have CDKN1C mutation - cell cycle regulator that broadly inhibits multiple CDKs
Increased risk of heptoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma
SX = Organomegaly, macroglossia, hemihypertropgym omphalocele, adrenal cytomegaly
