week 6

Question 1

———: The effect that mutations in a single gene have on multiple body systems

Answer 1

Pleiotropy

Question 2

Syndroms that exhibit Pleiotropy

Answer 2

Mafan, Tbc
(multisystem involvement)

Question 3

malformation of Cortical development (MCD) during the proliferation phase

Answer 3

• Polymicrogyria (PMG)
• Schizencephaly

Question 4

Malformations of Cortical development during the Organization phase

Answer 4

• Hemimegalencephaly
• Focal cortical dysplasia
• Microcephaly

Question 5

Malformations of cortical development during the Migration phase

Answer 5

• Lissencephaly (classical, cobblestone)
• Subcortical band heterotopia (SCBH)
• Periventricular nodular heterotopia (PVNH)
• Focal gray matter heterotopia

Question 6

disease charcaterized by “Smooth brain”
+ what type of malformation is it caused by?

Answer 6

Lissencephaly caused by Cortical malfromations during Migration

Question 7

AD cases of Classical Lissencephaly is caused by mutatios in —— on chromosone –q–

Answer 7

Classical Lissencephaly (LIS1) is caused by mutatios in LIS1 on chromosone 17q13.3

Question 8

XL forms of Classical Lissencephaly is caused by mutations on ——- gene, on chromosome –q–

Answer 8

XL forms of Classical Lissencephaly is caused by mutations on DCX gene, on chromosome Xq23

Question 9

Cobbelstone lissencephaly is an — disorder caused by mutations in ——, ——-, ——, —–

Answer 9

Cobbelstone lissencephaly is an AR disorder caused by mutations in FCMR, FRKP, PMOT1, POMT2 ,LARGE, POMGnT1

Question 10

Subcortical Band Heterotopia - SBH is caused by what type of Malformation?

Answer 10

cortical malforamtion during Migration

Question 11

Subcortical Band Heterotopia - SBH is an —, caused by —- mutations on chromosome —-

Answer 11

Subcortical Band Heterotopia - SBH is an AR, caused by DCX mutations on chromosome Xq23

Question 12

Loss of function mutations of the RET gene can cause

Answer 12

1) Hirschsprung disease
2) Renal agenesis
3) CAKUT (congenital anomalies of the kidney and urinary tract)

Question 13

Hirchsprung disease is an — disorder caused by —- mutations in –

Answer 13

Hirchsprung disease is an AD disorder caused by Loss of function mutations in RET

Question 14

—: A developmental disorder caused by absence of enteric ganglia along a variable length of intestine (neurocristopathy)

Answer 14

Hirschsprung disease

Question 15

Mowat-Wilson Syndrome is an — caused by mutations in —– gene on chromosome -q–

Answer 15

Mowat-Wilson Syndrome is an AD caused by mutations in ZEB2 gene on chromosome 2q22

Question 16

CM of Mowat-Wilson Syndrome

Answer 16

• Severe developmental delay with little or no speech
• Characteristic cranio-facial dysmorphism
• Microcephaly
• Epilepsy
• Hirschsprung disease or constipation
• Congenital heart disease
• Hypotonia
• Chracteristic uplifted ear lobes + dimple in the middle
• Friendly + happy personality
• Deep set and widely spaced eyes

Question 17

congenital anomalies of kidney and lower urinary tract (CAKUT) is an —— disorder caused by mutations in —— or ——- or ——- gene

Answer 17

congenital anomalies of kidney and lower urinary tract (CAKUT) is an AD disorder caused by mutations in RET or RET Ligand GDNF or -co-receptor GFRa1 gene

Question 18

CAKUT is genetically —–

Answer 18

Hetrogenous

* when diffrent gene mutations cause the same disease/condition

Question 19

Multiple Endocrine Neoplasia type 2 is caused by ——- mutations on ——

Answer 19

Multiple Endocrine Neoplasia type 2 is caused by Gain of function mutations on RET oncogene

Question 20

Tumors associated w/ MEN2

Answer 20

1) Medullary thyroid carcinoma (A, B)
2) Phaeochromocytoma (A, B)
3) Parathyroid adenoma/ hyperplasia (A)
4) Mucosal neuromas (B)
5) Ganglioneuromatosis of GI tract (B)

Question 21

Neurocristopathies are caused by —- mutations in —– gene

Answer 21

Neurocristopathies are caused by AD mutations in PAX3 gene

Question 22

Types of Neurocristopathies

Answer 22

Waardenburg syndrome (WSI & III)

Question 23

CF of Waardenburg Syndrome I

Answer 23

(auditory-pigmentary disorder)
– Sensorineural deafness
– Dystopia canthorum
– Pigmentary abnormalities of eyes, hair and skin

Question 24

Waardenburg syndrome type IV (WaardenburgShah syndrome) are caused by mutations in ——, —— and —– gene

Answer 24

Waardenburg syndrome type IV (WaardenburgShah syndrome) are caused by mutations in EDNRB, EDN3 and SOX10 gene

Question 25

CM of Waardenburg syndrome type IV (WaardenburgShah syndrome)

Answer 25

combine of - Pigmentary abnormalities, - hearing loss and - Hirschsprung disease

Question 26

**-----------** is a congenital anomaly that results from the primary **disturbance** of normal **morphogenetic mechanisms** **(e.g.----------)**

Answer 26

Malformation , e.g, Cleft lip

Question 27

**-----------** is a congenital anomaly caused by **distortion** of the developing embryo as a result of the application of extrinsic physical force **(e.g.------)**

Answer 27

Deformation, e.g., Talipes Equinovarus

Question 28

**---------** is a congenital anomaly which is the result of the destruction of fetal structures which have been developing normally **(e.g.,-------)**

Answer 28

Disruption, e.g., Amniotic band

Question 29

**----------**: Abnormal cellular organisation or function within a specific tissue type throughout the body, resulting in apparent structural changes

Answer 29

Dysplasia

Question 30

**----------**: is a pattern of congenital anomalies that are themselves the result of another, primary defect

Answer 30

**Sequence**

Question 31

Examples of Sequence congenital anomalies

Answer 31

1) **Oligohydramnios sequence**: renal dysplasia/ agenesis causes oligohydramnios which in **turn causes talipes** and **micrognathia** (deformation) and **pulmonary hypoplasia** **2) Pierre-Robin sequence:** mandibular underdevelopment causes tongue displacement, airway compromise and disturbed palatal fusion resulting in cleft palate

Question 32

CM of Oligohydramnios sequence

Answer 32

renal dysplasia/ agenesis causes oligohydramnios which in turn causes **talipes and micrognathia (deformation) and pulmonary hypoplasia**

Question 33

CM of Pierre-Robin Sequence

Answer 33

1) Potential fatal respiratory collapse 2) Feeding difficulties 3) Failure to thrive 4) Communication issues

Question 34

Syndromic forms of Pierre-Robin Sequence

Answer 34

- Stickler syndrome - 22q11.2 microdeletion - Various others

Question 35

Stickler syndrome is an **------** disorder caused by mutations in **------**

Answer 35

Stickler syndrome is an **AD** disorder caused by mutations in **COL2A1 (12q13), COL11A1 (1p21), COL11A2 (6p21)**

Question 36

CF of Stickler syndrome

Answer 36

* Facial dysmorphism (**flat mid-face, small nose, micrognathia**) * **Cleft palate** * Ocular features **(high myopia, retinal detachment, cataracts)** * **Sensorineural** or mixed hearing loss * Mild **spondylo-epiphyseal dysplasia with arthropathy**

Question 37

CF of 22q11.2 Deletion Syndrome

Answer 37

* **C**ardiac abnormalities * **A**bnormal facies * **T**hymic hypoplasia * **C**left palate * **H**ypocalcaemia | mnemonic : CATCH-22

Question 38

**------------** is a non-random group of congenital developmental anomalies (at least 2) that occur together more frequently than would have been expected by chance and where causal relationship has not been identified

Answer 38

Association | * these anomalies are idopathic

Question 39

CF of VACTERL association syndrome

Answer 39

* **V**ertebral * **A**norectal * **C**ardiac * **T**racheo- * **E**sophageal * **R**enal * **L**imb

Question 40

# *** CF of CHARGE syndrome

Answer 40

* **C**oloboma * **H**eart defects * **A**tresia (choanal) * **R**etardation of growth and development * **G**enital anomalies * **E**ar anomalies

Question 41

CHARGE syndrome is due to **-------** mutatios

Answer 41

heterozygous CHD7