Exam 1: Red Flags/Key Phrases

Question 1

Unsafe Immunization during pregnancy

Answer 1

MMR, Varicella, Oral Polio, and BCG for TB

Question 2

Pregnancy Category X drugs

Answer 2

Warfarin (coumadin) and isotretinoin (acutein). Note: Lisinopril is category D.

Question 3

APA + AMA Detail

Answer 3

NO increase in fetal autosomal aneuploidy in APA but most common aneuploidy in AMA is autosomal trisomy

Question 4

Seizure Disorder in Pregnancy

Answer 4

Avoid Valproate and Carbamazepine

Question 5

Function of SRY and PAR1+2

Answer 5

SRY = Codes for TDF (testis determining factor) + Leydig/Sertoli Effects.

PAR 1 = required for XY pairing during spermatogensis

Question 6

Male Sex Determination Genes + Function

Answer 6

SRY = most important
SRY + SF1 = upregulates SOX-9 + F6F9
SOX-9 + F6F9 = self feedback loop = male development in XY

SOX-9 = leads to change from pre-sertoli to sertoli cells
F6F9 (fibroblast growth factor) = in balance between female pathway (WNT4/RSPO/Beta-caterin) and shift to F6F9 leads to male sexual development

Note: DAX-1 = necessary for gonadal development in both sexes

Question 7

Female Sex Determination Genes + Function

Answer 7

in XX Gonads = WNT4/RSPO/Beta-Catenin dominant SOX-9/F6F9

WNT4 Pathway = ovarian development + mullerian duct formation
RSPO1 = Binds and stabilizes Beta-caternin which regulates gene transcription. Also degrades Sox-9 in ovaries.

Note: WNT4 + RSPO1 = positive self feedback loop.
Note: Estrogen not required for female differentiation

Question 8

Clinical: Campomelic Dwarf/Syndrome/Dysplasia

Answer 8

Poor dysfunctional bone structure due to absence of SOX-9 (control bone growth in fetus).

Question 9

Female Infertility Scheme: Unexplained infertility Treatment

Answer 9

3-4 Cycles of Clomiphene Citrate (blocks negative feedback of hypothalamus, acts as estrogen agonist.)
Add Intrauterine insemination, 6 cycles
1-3 cycles of FSH and IUI
IVG

Question 10

Female Infertility Scheme: Labs

Answer 10

Day 21 Progesterone (if 35 yo + FH of POF (if

Question 11

Undermasculinzed Male (DSD)

(disorders of testosterone biosynthesis)
CYP450 Oxireductase Deficiency
17 alpha - Hydroxylase Deficiency
17 beta - HSD Deficiency

Answer 11

Ambigous Genitalia: Gonads Palpable:

46XY (normal)

CYP450 Oxireductase Deficiency = Cause of Antley Bixler Syndrome (skeletal dysplasia, ambigous genitalia, abnormal steroidgenesis)
17 alpha - Hydroxylase Deficiency = Salt and Water Retention: HTN
17 beta - HSD Deficiency = Undescended Testes

Question 12

Mixed Gonadal Dysgenesis

Denys-Drash Syndrome!

Answer 12

Ambigous Genitalia: Gonads Palpable:

45XO/45XY = most common mosaicism 
(Physical = ovary and testes side, both on the same genitalia) b

Streak Gonads and Testis on opposite sides: Increase risk of wilms tumor, gonadoblastoma, and dysgerminoma

Denys-Drash Syndrome (WT1 gene mutation) - above + renal failure (nephropathy)

Question 13

Mayer-Rokintansky Syndrome

Answer 13

Ambigous Genitalia: Gonads Not Palpable:

Mutation of WNT4 gene

Congenital absence of uterus and proximal vagina BUT Ovaries and fallopian tubes are present (normal FSH and LH)

Question 14

hemochromatosis

Answer 14

Male Infertility: Endocrine

Genetic disorder of mucosal iron transport resulting in tissue deposition in the pituitary tissues = Decrease FSH and LH and therefore testosterone

Question 15

Mumps Orchitis

Answer 15

Male Infertility: Testicular (primary hypogonadism)

Infection: damage to seminiferous tubules as well as leydig cell damage (decrease testosterone)

Question 16

Prader Willi Syndrome

Answer 16

Male Infertility: Testicular (primary hypogonadism)

Most common syndromic form of obesity
Symptoms = low muscle tone in nursury

Question 17

Masculinized Female (DSD)

Answer 17

46XX Congenital Adrenal Hyperplasia

17 OH Progesterone Elevated! (Decreased cortisol, increased testosterone)

21 Hydroxylase Deficiency: Salt wasters
Virilization in Females, “Little Hercules” in Males

TX: Dexamethasone

Question 18

Normal Sperm Values

Answer 18

Volume = greater than or equal to 1.5 ml
Sperm Concentration = GTOET 15 million sperm/ml
Normal Morphology = GTOET 4%
Progressive Motility = GTOET 32%

Also, test if decrease fructose = associated with congenital absence of vas deferns, seminal vesicles, or ejaculatory duct obstruction.

Question 19

Morning Testosterone

Answer 19

if Low = primary hypogonadism (testicular/anatomic)

Question 20

Kallman Syndrome + Genes and Interaction

Answer 20

KAL1 (x linked) = loss of anosmin

KAL1 + FGFR1 interaction with Heparin
KAL1 binds to FGFR1 = inhibits binding of FGFR1 to FTFR2 + Heparin to form complex
KAL1 binds to heparin = activates and promotes dimerization via FGF2 + heparin binding.

FGF8 = ligand for FGFR1, SX: Hearing loss, high arched palate, cleft stuff.

Question 21

1st + 2nd Trimester Serum Markers : Trisomy 21

Answer 21

1st Trimester: Trisomy 21: ↑ human chorionic gonadotropin (hCG), ↓ Pregnancy Associated Plasma Protein A (PAPP-A, metalloproteinase). 80%* (+ maternal age)

2nd Trimester: 2nd Tri Serum Markers – Trisomy 21
o Triple screen: ↓ α-fetoprotein (AFP or MSAFP), ↑ human chorionic gonadotropin (hCG), ↓ Unconjugated estriol (uE3, produced by placenta)
• Detection rate ~60%, false positive rate ~5%
o Quad screen: triple screen + ↑ dimeric inhibin A (InhA, produced by placenta, inhibits FSH)
• Detection rate ~75%

Question 22

1st + 2nd Trimester Serum Markers : Trisomy 18

Answer 22

1st Trimester:
o Trisomy 18: ↓ hCG, ↓ PAPP-A. 90%*
o Trisomy 13: ↓ hCG, ↓ PAPP-A. 90%*

2nd Tri Serum Markers- Trisomy 18
o Triple screen: ↓ α-fetoprotein (AFP or MSAFP), ↓ human chorionic gonadotropin (hCG), ↓ Unconjugated estriol (uE3)
• Detection rate ~80%, false positive rate ~0.6%
o Not as well studied: triple screen + ↓ dimeric inhibin A (InhA)
• Preliminary results detection rate 100%, false positive rate ~0.3%

Question 23

1st and 2nd Trimester Ultrasound

Answer 23

1st Tri Ultrasound Screen (Pictures)
o ↑ nuchal translucency: collection of fluid at the back of fetal neck
o ↑ abnormal high-impedance flow through ductus venosus
o Tricuspid regurgitation
o No visualization or hypoplasia of nasal bone

2nd Tri Ultrasound Screen
o ↑ nuchal fold = refers to the nuchal translucency
o ↓ humerus length
o Renal pelvic dilation – kidney enlargement
o Intracardiac echogenic foci – bright spots on the heart
o Choroid plexus cyst – choroid plexus produces cerebrospinal fluid “spongy layer” of cells and blood vessels
o If these things appear in isolation, doesn’t mean too much, apparently it’s common.