Chapter 10

Question 1

Primary cause of death in infants younger than 1 year

Answer 1

Congenital malformations, deformations, and chromosomal abnormalities

Question 2

Primary cause of death in children age 1-4

Answer 2

Accidents (unintentional injury)

Question 3

Primary cause of death in children 5-9

Answer 3

Accidents (unintentional injury)

Question 4

Primary cause of death in children 10-14

Answer 4

Accidents (unintentional injury)

Question 5

Primary errors of morphogenesis in which there is intrinsically abnormal developmental process; typically multifactorial in origin

Answer 5

Malformations

Question 6

Examples of malformations

Answer 6

Congenital heart defects
Anencephaly
Polydactyly or syndactyly
Cleft palate

Question 7

_____ result from secondary destruction of an organ or body region previously normal in development; arise from extrinsic disturbance in morphogenesis

Answer 7

Disruption

Question 8

Examples of disruption

Answer 8

Amniotic bands

Question 9

Example of deformation

Answer 9

Clubfeet

Question 10

Fetal phenotype associated with Potter sequence

Answer 10

Flattened facies
Positional abnormalities of hands and feet
Hips may be dislocated
Hypoplastic lungs
Nodules in amnion

Question 11

General cause of holoprosencephaly

Answer 11

Genetic — mendelian inheritance

Question 12

Clinical features of fetal alcohol syndrome

Answer 12

Growth retardation
Microcephaly
Short palpebral fissures
Maxillary hypoplasia
Psychomotor disturbance

Question 13

Etiology/associations with neonatal respiratory distress syndrome

Answer 13

Excess sedation of mother, fetal head injury during delivery, aspiration of blood or amniotic fluid, intrauterine hypoxia from cord around neck

Associated with male gender, maternal diabetes, and delivery by C section

Question 14

What therapy can be administered prior to birth if the fetuses lungs are underdeveloped?

Answer 14

Glucocorticoids

Question 15

2 major complications of ventilation used to treat neonatal RDS

Answer 15

Retinopathy of prematurity (retrolental fibroplasia) — leads to retinal vessel proliferation

Bronchopulmonary dysplasia — striking decrease in alveolar septation

Question 16

Infants who recover from neonatal RDS are at increased risk for what conditions?

Answer 16

Patent ductus arteriosus
Intraventricular hemorrhage
Necrotizing enterocolitis

Question 17

Etiology/associations with necrotizing enterocolitis

Answer 17

Most common in premature infants

Most cases associated with enteral feeding, suggesting that some postnatal insult (like introduction of bacteria) causes tissue destruction process

Inflammatory mediators

Question 18

What inflammatory mediator is implicated in necrotizing enterocolitis — playing a role in increasing mucosal permeability by promoting enterocyte apoptosis and compromising intercellular tight junctions?

Answer 18

PAF

Question 19

Define fetal hydrops and differentiate immune vs. nonimmune

Answer 19

Fetal hydrops = accumulation of edema fluid in fetus during intrauterine growth

Immune: type II HSR associated with Rh-group incompatibility

Nonimmune: most commonly associated with cardiovascular issues, chromosomal issues, or fetal anemia

Question 20

Morphology and clinical features of fetal hydrops

Answer 20

Pale fetus and placenta
Hepatosplenomegaly
Hyperplastic erythroid precursors in bone marrow
Extramedullary hematopoiesis in liver, spleen, kidneys, etc.
Jaundice d/t unconjugated bili
Kernicterus

Question 21

2 primary routes by which perinatal infections are acquired

Answer 21

Transcervically — most bacterial and a few viral; inhalation of infected amniotic fluid or passing through infected birth canal

Transplacentally (hematologic) — most parasitic and viral, some bacterial (listeria, treponema); gain access to fetal bloodstream via chorionic villi

Question 22

Transplacentally acquired pathogen resulting in erythema infectiosum, characterized by spontaneous abortion, stillbirth, hydrops fetalis, and congenital anemia

Answer 22

Parvovirus B19

Question 23

Describe TORCH group of infections in terms of clinical features and chronic sequelae

Answer 23

Fever, encephalitis, chorioretinitis, HSM, pneumonitis, myocarditis, hemolytic anemia, vesicular or hemorrhagic skin lesions

Chronic sequelae: growth and mental retardation, cataracts, congenital cardiac anomalies, bone defects

Question 24

Enzyme deficiency and clinical presentation of PKU

Answer 24

Enzyme def: PAH

Clinical presentation: hyperphenylalaninemia — severe mental retardation by 6 mos, seizures and other neurologic problems, decreased pigmentation of hair and skin, eczema, strong musty odor to urine

Question 25

Enzyme deficiency and clinical presentation of galactosemia

Answer 25

2 possible enzyme def: most common is lack of galactose-1-phosphate uridyl transferase (GALT), rare is deficiency of galactokinase Results in accumulation of galactose-1-phosphate in liver, spleen, lens, kidneys, heart muscle, cerebral cortex, and erythrocytes. Also accumulation of galactitol and galactonate in tissues. Liver, eyes, and brain get worst damage — hepatomegaly, cataracts, loss of nerve cells, gliosis, brainstem edema Others: FTT, vomiting, diarrhea within a few days of milk ingestion, persistent jaundice, mental retardation within 6-12 mos, aminoaciduria, E coli septicemia, hemolysis, and coagulopathy

Question 26

Inheritance of PKU and galactosemia

Answer 26

AR

Question 27

Inheritance of CF

Answer 27

AR

Question 28

CF is associated with what other conditions that may harbor CFTR mutations?

Answer 28

Idiopathic chronic pancreatitis Late-onset chronic pulmonary disease Idiopathic bronchiectasis Obstructive azoospermia

Question 29

Changes in airway vs. sweat cell transport in CF

Answer 29

Airway: ENaC activity increases, markedly augmenting Na uptake across apical membrane Sweat glands: ENaC activity decreases, producing salty sweat

Question 30

Result of possibly abnormal bicarbonate conductance in CF

Answer 30

Decreased luminal pH —> pancreatic insufficiency

Question 31

Congenital absence of vas deferens is associated with what condition?

Answer 31

CF

Question 32

Clinical features of CF

Answer 32

Chronic lung disease secondary to recurrent infections (common agent is pseudomonas aeruginosa —> lower lungs) and recurrent sinonasal polyps Pancreatic insufficiency (results in ADEK deficiency and edema) Steatorrhea and hepatic cirrhosis Malnutrition characterized by large, foul smelling stools, abdominal distension, and poor weight gain Intestinal obstruction (meconium ileus), polyposis Male infertility

Question 33

Morphological findings in SIDS cases

Answer 33

Multiple petechiae Congested lungs with vascular engorgement +/- pulmonary edema Astrogliosis of brainstem and cerebellum Persistent hepatic extramedullary hematopoiesis and periadrenal brown fat

Question 34

Delineate heterotopia from hamartoma

Answer 34

Heterotopia (choristoma): microscopically normal cells or tissues that are present in abnormal locations Hamartoma: excessive focal overgrowth of cells and tissues native to the area in which it occurs

Question 35

2 types of lymphatic tumors of childhood

Answer 35

Lymphangiomas: hamartomatous or neoplasic; characterized by cystic and cavernous spaces, tend to increase in size after birth Lymphangiectasis: represent abnormal dilations of preexisting lymph channels, usually presents as diffuse swelling of part or all of an extremity

Question 36

2 types of fibrous tumors seen in childhood

Answer 36

Fibromatosis: sparsely cellular proliferations of spindle-shaped cells Congenital-infantile fibrosarcomas: richly cellular lesions indistinguishable from fibrosarcomas in adults

Question 37

Characteristic chromosomal translocation associated with congenital-infantile fibrosarcomas

Answer 37

t(12;15)(p13;q25) - results in generation of ETV6-NTRK3 fusion transcript

Question 38

Sites of involvement for neuroblastic tumors

Answer 38

Sympathetic ganglia | Adrenal medulla

Question 39

Morphologic features of neuroblastic tumors

Answer 39

Presence of neuropil on histology, as well as Homer Wright pseudorosettes Presence of ganglion cells + primitive neuroblasts = ganglioneuroblastoma Presence of ganglion cells without neuroblasts = ganglioneuroma

Question 40

Clinical course of neuroblastic tumors

Answer 40

Large abdominal masses, fever, possibly weight loss Metastasize widely — liver, lungs, bones, bone marrow, periorbital region, skin “blueberry muffin baby” Production of catecholamines = important diagnostic feature is VMA and HVA

Question 41

Favorable prognostic factors for neuroblastic tumors

Answer 41

``` Stage 1, 2A, 2B, 4S Age <18 mos Presence of schwannian stroma and gangliocytic differentiation Low mitosis-karyorrhexis index Hyperdiploid (whole chromosome gains) No amplification of MYCN No loss of Chr 1p or 11q Presence of TRKA expression No TRKB expression or mutations of neuritogenesis genes ```

Question 42

3 groups/types of Wilms tumor and their identifying feature(s)

Answer 42

1. WAGR syndrome - WT1 deletion, aniridia, genital anomalies, mental retardation 2. Denys-Drash syndrome - gonadal dysgenesis, renal failure, risk of gonadoblastoma, precursors are nephrogenic rests; missense mutation in WT1 3. Beckwith-Wiedmann syndrome - organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly; heterogenous abnormalities in 11p15.5

Question 43

In which group of Wilms tumor is there increased risk of rhabdomyosarcoma, hepatoblastoma, pancreatoblastoma, and adrenocortical tumors?

Answer 43

Beckwith-wiedmann syndrome

Question 44

Wilms tumor, what is the difference if it is caused by germline mutations vs. sporadic mutations?

Answer 44

Germline —> bilateral masses Sporadic —> unilateral

Question 45

Morphologic features of wilms tumor

Answer 45

Classic triphasic combo of blastemal, stromal, and epithelial cell types Some tumors show anaplasia, usually with TP53 mutations (confers resistance to chemo)

Question 46

Clinical course of wilms tumor

Answer 46

Most present with large abdominal mass that may be unilateral or grow to extend over midline Hematuria, abdominal pain, intestinal obstruction, HTN Pulmonary metastases common at time of dx