Genetic and Developmental disorders

Question 1

Development of multiple neurofibromas and pigmented skin lesions

Answer 1

Neurofibromatosis type 1

–NF-1 tumor suppressor–autosomal dominant pattern of inheritance

Question 2

Factor VIII deficiency with prolonged PTT

X-linked recessive condition

Answer 2

Hemophilia A

Question 3

Defects in Fibrillin from missense mutations in the Fibrillin gene

• -loss of vision/subluxation of lens
• -systolic click
• -mitral valve floppy
• -dilated aortic arch

Answer 3

Marfan syndrome

Question 4

Group of inherited disorders that mostly affect skin, joints, and blood vessels

decrease in tensile strength with a deficiency of enzyme lysyl hydroxylase–defect in type 1 and 3 collagen

Answer 4

Ehlers-Danlos

Question 5

Ion channel mutation

Answer 5

Cystic fibrosis–mutations in CFTR gene encoding Cl- ion channels

Question 6

Receptor mutations

Answer 6

Familial hypercholesterolemia–abnormal LDL receptor

Autosomal dominant

Question 7

Cherry red spot in the retina–mutations in the gene that encodes for hexosaminidase A

Motor incoordination
severe MR
death

Answer 7

Tay-Sachs Dz

Question 8

Neuro involvement–motor and mental impairment
Hepatosplenomegaly
accumulation of FOAMY macrophages

sphingomyelinase deficiency

Answer 8

Niemann-Pick dz

Question 9

Hepatomegaly
Renomegaly
impaired gluconeogen–hypoglycemia and hyperlipidemia

G6Pase deficiency

Answer 9

Von Gierke Dz

Question 10

bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen

deficiency of glucocerebrosidase

Answer 10

Gaucher Dz type 1 doesn’t involve CNS

Type 2 & 3 involve CNS

Question 11

Mucopolysaccharidose (MPS) seen in urine and macrophages(balloon cells)
Deficiency of a-1-iduronidase

Coarse facial features
Corneal clouding
Joint Stiffness
Hepatosplenomegaly
MI--subendothelial coronary arterial deposits

Answer 11

Hunter syndrome—X-linked recessive or Hurler syndrome

Question 12

Glucosidase deficiency–a-1,4-glucosidase

Cardiomegaly/heart failure in infancy—glycogen stored in myocardium

Answer 12

Pompe Dz

Question 13

Glycogen storage Dz
Deficiency of muscle phosphorylase–muscle cramping

Brown urine seen in 50% of cases

Answer 13

McArdle Dz

Question 14

Mutation to RBC membrane cytoskeletal protein

Answer 14

Abnormal spectrin– Hereditary spherocytosis

Question 15

Alkaptonuria with deposition of a blue-black pigment in joints –ochronosis

Answer 15

Homogentisic acid oxidase deficiency

Question 16

250-4000 tandem repeats of the trinucleotide sequence CGG- subsequent male offspring have more severe dz compared to earlier generations

Answer 16

Fragile X syndrome

Question 17

Males and females affected from dz–BUT males cannot transmit the dz to offspring

CNS and muscle involvement–cells dependent on ox/phos

Answer 17

Mitochondrial mutation

Question 18

Deformation that results from destruction of irreplaceable normal fetal tissue–rupture of the amnion with formation of fibrous bands that encircles parts of the fetus

Answer 18

Amniotic bands–early amnion disruption

Question 19

problems occurring from 9th week-term

Answer 19

Deformations

Question 20

Problems occurring from 3-9wks

Answer 20

Malformations

Question 21

Caused from renal a genesis/cystic Dz of the kidneys

Flat facial features (potter facies)
compression of skull vault
Dysplastic/displaced ears
Underdeveloped chest wall
club feet (talipes equinovarus)

Answer 21

Oligohydramnios

Question 22

Cardiac/neural/craniofacial defects

Down regulation of TGF-B signaling pathway and affect the expression of HOX genes (important for patterning of limbs/vetebrae/craniofacial structures

Answer 22

Retinoic acid embryopathy

Question 23

Fetal growth restriction–sparring of fetal brain

decrease size of placenta with oligo

Answer 23

Uteroplacental insufficiency

Question 24

Spirochetes crossing placenta during the 3rd trimester

Answer 24

Congenital syphilis

Question 25

``` Occurs during first trimester-can lead to abnormalities: cardiac--defects ocular skin cns hepatic ```

Answer 25

Congenital Rubella infection

Question 26

Hyperplasia of the fetal islets--after birth islets over function and cause hypoglycemia

Answer 26

Maternal DM

Question 27

common cause of congenital infection a term/peripartum

Answer 27

Group B streptococcus

Question 28

Preterm premature rupture of membranes due to infection infection in genital tract--causing release of collagenases and elastases--promoting rupture of membranes and release of prostaglandins that induce smooth muscle contraction and labor

Answer 28

Chorioamnionitis and funisitis--necrosis of the umbilical cord

Question 29

Most likely to produce severe CNS damage

Answer 29

Cytomegalovirus and toxoplasmosis

Question 30

Acquired via passage through birth canal

Answer 30

Herpetic congenital infections

Question 31

May cause a severe fetal anemia

Answer 31

Parvo virus

Question 32

Severe anemia and myocardial injury cause hydrops - brain often involved-- enlarged ventricles/encephalitis/necrosis - renal tubular epithelium can be infected - acquired--transplacentally/@birth/breast milk

Answer 32

Cytomegalovirus

Question 33

CNS findings--microcephaly/periventricular leukomalacia/calcifications Blind/deaf Through injection of poorly cooked contaminated food or changing cat litter

Answer 33

Toxoplasmosis

Question 34

IUGR with asymmetric growth--head normal later in gestation

Answer 34

Pregnancy induced HTN

Question 35

Infant small for gestational age usually no other problems noted increased risk for preterm premature rupture of membranes

Answer 35

Cigarette smoking during pregnancy

Question 36

Sustained, high does O2 therapy delivered with + pressure ventilation--to new born

Answer 36

Bronchopulmonary dysplasia

Question 37

Lack of sufficient surfactant to enable adequate ventilation after birth

Answer 37

Hyaline membrane dz

Question 38

complication of prematurity related to many factors: - intestinal ischemia - enterocyte apoptosis - bacterial overgrowth - formula feeding

Answer 38

Necrotizing enterocolitis

Question 39

Congenital condition resulting from an a ganglionic segment of distal colon---obstruction with distention ---NO bloody diarrhea

Answer 39

Hirschsprung Dz

Question 40

Typically incidental finding later in life associated with GI bleeding and ectopic gastric mucosa

Answer 40

Meckel Diverticulum

Question 41

Seen in setting of cystic fibrosis--can lead to obstruction in GI

Answer 41

Meconium ileus

Question 42

Maternal antibody coats fetal RBCs causing hemolysis - -+ coombs test - -fetal anemia--CHF and hydrops - -increased bilirubin level

Answer 42

Erythroblastosis fetalis

Question 43

Result of vascular anastomosis btwn halves of a monochorionic placenta - -Donor twin--smaller/decreased organ function/oligo - -recipient twin-- plethoric/hydrops/poly

Answer 43

Twin-Twin transfusion syndrome

Question 44

ABO incompatibility--IgG isohemaglutienus cross the placenta and bind to fetal cells - -mother blood type O - -Baby blood type A - -+ Coombs test

Answer 44

Immune Hydrops Fetalis

Question 45

Large, pink, intranuclear inclusions in bone marrow biopsy Can lead to in fetus: - profound fetal anemia - cardiac failure - hydrops fetalis

Answer 45

Paravovirus infection

Question 46

Caused by absence of functional phenylalanine hydroxyls genes Gives rise to hyperphenylalaninemia--impairs brain development and can lead to seizures - decreased pigmentation of skin and hair - "mousy" odor urine---phenylacetic acid

Answer 46

Phenylketonuria (PKU)

Question 47

Caused by Galactose-1-phosphate uridyltransferase deficiency--in born error of metabolism--autosomal pattern of inheritance severe liver Dz and cataracts

Answer 47

Galactosemia

Question 48

Lysosomal acid maltase deficiency--cardiomegaly and heart failure

Answer 48

Pompe Dz

Question 49

- Steatorrhea - autosomal recessive - 3-base pair deletion - respiratory infections--pseudomodas aeruginosa/burkholderia cepacia - formation of respiratory epithelial biofilms - sweat chloride - polymorphisms of MBL2 and TGFB1 genes

Answer 49

Cystic fibrosis

Question 50

No significant gross/microscopic autopsy findings | Abnormalities of serotonergic neural pathways in the medulla and respiratory tract stressor (sleeping prone)

Answer 50

Sudden infant death syndrome (SIDS)

Question 51

A birthmark often appearing as a rubbery, bright red nodule of extra blood vessels Most common tumor of infancy

Answer 51

Hemangioma

Question 52

Likely congenital/early childhood neoplasm

Answer 52

Tumor with the suffix blastoma

Question 53

Benign neoplasms composed of tissues derived from embryonic germ layers--midline location

Answer 53

Teratomas

Question 54

Loss of tumor suppression and development of Retinoblastoma--germline mutation

Answer 54

Inherited abnormal RB1 gene

Question 55

Occurs in 25% of neuroblastomas | Greater the # of copes--worse the prognosis

Answer 55

MYCN oncogene amplification

Question 56

Increased risk of development of Wilms tumor--childhood neoplasm arising in the kidney--deletion of the short arm of chromosome 11

Answer 56

WAGR syndrome

Question 57

GU defects a the first hit

Answer 57

WT1 loss

Question 58

Aniridia and CNS maldevelopment with MR

Answer 58

PAX6 loss

Question 59

can be found in the renal parenchyma adjacent to a wilma tumor and is precursor

Answer 59

Nephrogenic rests