Random Congenital Diseases

Question 1

What is the pathophysiology of Cystinuria?

Answer 1

Defect in dibasic amino acid transporter - lysine, arginine, ornithine, and cystine. Causes recurrent stone formation. Low urine pH is a risk factor.

Question 2

What is the pathophysiology of Kallmann syndrome?

Answer 2

Defective migration of GnRH-releasing neurons into the hypothalamus. Defective olfactory bulb (anosmia). Hypogonadotrophic hypogonadism.

Question 3

Pathophysiology of testicular feminization synbdrome?

Answer 3

Complete androgen insensitivity. 46XY, phenotypically female, but rudimentary vagina, absent uterus. Delayed secondary sex characteristics. Develops testes which should be surgically removed to prevent ca.

Question 4

Trisomy 21: signs

Answer 4

• Low AFP, estriol
• Increased beta-hCG, inhibin A
• Nuchal translucency on ultrasound
• On inspection
  
  • Flat facial features
  • Single palmar crease
  • Excess skin at nape of neck
  • Slanted palpebral fissures

Question 5

Associations: low AFP? elevated AFP?

Answer 5

low AFP: Down’s

elevated AFP:

• multiple gestation
• neural tube defects (spina bifida, anencephaly)
• abdominal wall defects (omphalocele, bladder extrophy)

Question 6

Edwards syndrome?

Answer 6

Trisomy 18

• Microphthalmia, low-set ears, small mandible (micrognathia)
• Microcephaly, neural tube defects, Arnold-chiari
• Clenched hands with overlapping fingers
• Rocker-bottom feet
• VSD, PDA
• Meckel’s diverticulum, malrotation

Question 7

Patau syndrome

Answer 7

Trisomy 13

• Microphthalmia
• Microcephaly, MR, holoprosencephaly
• Rocker-bottom feet
• Adominal wall defects (omphalocele etc)
• Cleft lip, palate, polydactyly

Question 8

Cri-du-chat syndrome

Answer 8

5p-

• Microcephaly, MR
• High pitched cry
• Epicanthal folds
• Cardiac abnormalities

Question 9

Williams syndrome

Answer 9

7q11.23-

• Elfin facies
• Hypercalcemia (sensitivity to vitamin D)
• MR but well-developed verbal skills
• extreme friendliness
• cardio problems

Question 10

DiGeorge and related?

Answer 10

22q11- (velocardiofacial syndromes)

• Defect in 3rd and 4th pharyngeal pouches
• Cleft palate, abnormal facies
• Thymic aplasia
• Cardiac defects

Question 11

Hypospadias, epispadias, and bifid scrotum

Answer 11

• Hypospadias: non-fusion of urethral folds (labia minora and vaginal vestibule in females)
• Epispadias: malposition of genital tubercle
• Bifid scrotum: nonfusion of labioscrotal folds (labia majora in females)

Question 12

Turner syndrome: signs

Answer 12

45XO

• Short stature, webbed neck, low posterior hairline, shield chest, widely spaced nipples
• Streak gonads - few atretic follicles
• No secondary sex characteristics
• Cardiac: coarctation, bicuspid aortic valve
• infantile: Cystic hygromas

Question 13

Common polygenic disorders (8)

Answer 13

• Androgenic alopecia (also X-linked?)
• Epilepsy
• Ischemic heart dz
• Schizophrenia
• Glaucoma
• Hypertension
• Malignancy
• Type II DM

Question 14

Ciliopathies

Answer 14

• Kartagener syndrome
  
  • primary ciliary dyskinesia: dynein arms nonfunctional
  • chronic sinusitis and bronchiectasis
  • infertility
  • situs inversus
• Bardet-biedl syndrome
  
  • blindness
  • polydactyly
  • obesity
• ADPKD and ARPKD
  
  • AD
    
    • adult onset, large cysts
    • flank pain, hematuria, hypertension
    • associated with berry aneurysms, mitral valve prolapse
  • AR: infantile presentation; associated with congenital hpeatic fibrosis

Question 15

What cells produce Mullerian inhibitory factor (MIF)?

Answer 15

Sertoli cells

Question 16

How many chorions/amnions for

• Dizygotic twins
• Monozygotic twins, early separation
• Monozygotic twins, late separation
• Monozygotic twins, very late separation

Answer 16

• Dizygotic twins - always dichorionic and diamniotic; placenta may fuse
• Monozygotic
  
  • 0-4 days separation: diamniotic, usually monochorionic (rarely dichorionic)
  • 8-12 days separation: monoamniotic, monochorionic; increased risk of fetal death due to umbilical cord entanglement
  • 12+ days separation: can be conjoined twins

Question 17

McCune-Albright - sx. What’s special?

Answer 17

Defect in G-protein signaling

**Unilateral **Polyostotic fibrous dysplasia (bone replaced)

Endocrine abnormalities (precocious puberty)

Cafe au lait spots

Mosaicism - postzygotic mutation

Question 18

Fanconi Anemia

Answer 18

DNA DSB/crosslink repair. Pancytopenia, tumors & leukemia, short stature.

Question 19

Osler Weber Rendu - aka?

Answer 19

Hereditary Hemorrhagic Telangiectasia. Name says it all - GI bleeds, etc. Autosomal Dominant.

Question 20

Rett syndrome

Answer 20

X-linked dominant disorder (females only; males die in utero). Cerebroatrophic hyperammonemia. Develop normally then regress.

Question 21

Peutz-Jaeghers syndrome. Mutation, inheritance, sx.

Answer 21

Mutation in STK11 on chromosome 9.

• Pigmented mucocutaneous macules (first) - mouth, hands, feet.
• hamartomatous polyps in GI tract - can present with bleeding or pain

Question 22

Alkaptonuria - defect, effects. What is the serious effect?

Answer 22

Homogentisic acid oxidase in tyrosine degradation pathway.

Urine darkens upon standing; ochronosis (darkening of tissues eg sclera, ears).

Arthritis can be significant sequela.

Question 23

Cholesterol ester storage disease. Pathophys, sx.

Answer 23

AKA Wolman disease. Deficient lysosomal acid lipase.

Hepatosplenomegaly, fibrosis, hyperlipidemia with low-normal HDL, lymphadenopathy.

Can look a bit like Niemann Pick.

Question 24

von-Hippel-Lindau. Mechanism of hemangioblastomas? Other Sx?

Answer 24

mutation in VHL-1 gene chr 3.

Normally, this gene suppresses expression of HIF-1a; get cavernous hemangiomas in skin, mucosa, organs.

VHL-1 is a TSG: bilateral renal cell carcinoma, pheochromocytoma