week 6 Flashcards
———: The effect that mutations in a single gene have on multiple body systems
Pleiotropy
Syndroms that exhibit Pleiotropy
Mafan, Tbc
(multisystem involvement)
malformation of Cortical development (MCD) during the proliferation phase
- Polymicrogyria (PMG)
- Schizencephaly
Malformations of Cortical development during the Organization phase
- Hemimegalencephaly
- Focal cortical dysplasia
- Microcephaly
Malformations of cortical development during the Migration phase
- Lissencephaly (classical, cobblestone)
- Subcortical band heterotopia (SCBH)
- Periventricular nodular heterotopia (PVNH)
- Focal gray matter heterotopia
disease charcaterized by “Smooth brain”
+ what type of malformation is it caused by?
Lissencephaly caused by Cortical malfromations during Migration
AD cases of Classical Lissencephaly is caused by mutatios in —— on chromosone –q–
Classical Lissencephaly (LIS1) is caused by mutatios in LIS1 on chromosone 17q13.3
XL forms of Classical Lissencephaly is caused by mutations on ——- gene, on chromosome –q–
XL forms of Classical Lissencephaly is caused by mutations on DCX gene, on chromosome Xq23
Cobbelstone lissencephaly is an — disorder caused by mutations in ——, ——-, ——, —–
Cobbelstone lissencephaly is an AR disorder caused by mutations in FCMR, FRKP, PMOT1, POMT2 ,LARGE, POMGnT1
Subcortical Band Heterotopia - SBH is caused by what type of Malformation?
cortical malforamtion during Migration
Subcortical Band Heterotopia - SBH is an —, caused by —- mutations on chromosome —-
Subcortical Band Heterotopia - SBH is an AR, caused by DCX mutations on chromosome Xq23
Loss of function mutations of the RET gene can cause
1) Hirschsprung disease
2) Renal agenesis
3) CAKUT (congenital anomalies of the kidney and urinary tract)
Hirchsprung disease is an — disorder caused by —- mutations in –
Hirchsprung disease is an AD disorder caused by Loss of function mutations in RET
—: A developmental disorder caused by absence of enteric ganglia along a variable length of intestine (neurocristopathy)
Hirschsprung disease
Mowat-Wilson Syndrome is an — caused by mutations in —– gene on chromosome -q–
Mowat-Wilson Syndrome is an AD caused by mutations in ZEB2 gene on chromosome 2q22
CM of Mowat-Wilson Syndrome
- 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
congenital anomalies of kidney and lower urinary tract (CAKUT) is an —— disorder caused by mutations in —— or ——- or ——- gene
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
CAKUT is genetically —–
Hetrogenous
* when diffrent gene mutations cause the same disease/condition
Multiple Endocrine Neoplasia type 2 is caused by ——- mutations on ——
Multiple Endocrine Neoplasia type 2 is caused by Gain of function mutations on RET oncogene
Tumors associated w/ MEN2
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)
Neurocristopathies are caused by —- mutations in —– gene
Neurocristopathies are caused by AD mutations in PAX3 gene
Types of Neurocristopathies
Waardenburg syndrome (WSI & III)
CF of Waardenburg Syndrome I
(auditory-pigmentary disorder)
– Sensorineural deafness
– Dystopia canthorum
– Pigmentary abnormalities of eyes, hair and skin
Waardenburg syndrome type IV (WaardenburgShah syndrome) are caused by mutations in ——, —— and —– gene
Waardenburg syndrome type IV (WaardenburgShah syndrome) are caused by mutations in EDNRB, EDN3 and SOX10 gene
CM of Waardenburg syndrome type IV (WaardenburgShah syndrome)
combine of
- Pigmentary abnormalities,
- hearing loss and
- Hirschsprung disease
———– is a congenital anomaly that results from
the primary disturbance of normal morphogenetic mechanisms (e.g.———-)
Malformation , e.g, Cleft lip
———– is a congenital anomaly caused by distortion of the developing embryo as a result of the application of extrinsic physical force (e.g.——)
Deformation, e.g., Talipes Equinovarus
——— is a congenital anomaly which is the result of the destruction of fetal structures which have been
developing normally (e.g.,——-)
Disruption, e.g., Amniotic band
———-: Abnormal cellular organisation or function within a specific tissue type throughout the body, resulting in apparent structural changes
Dysplasia
———-: is a pattern of congenital anomalies that are themselves the result of another, primary defect
Sequence
Examples of Sequence congenital anomalies
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
CM of Oligohydramnios sequence
renal dysplasia/ agenesis causes oligohydramnios which in turn causes talipes and micrognathia (deformation) and pulmonary hypoplasia
CM of Pierre-Robin Sequence
1) Potential fatal respiratory collapse
2) Feeding difficulties
3) Failure to thrive
4) Communication issues
Syndromic forms of Pierre-Robin Sequence
- Stickler syndrome
- 22q11.2 microdeletion
- Various others
Stickler syndrome is an —— disorder caused by mutations in ——
Stickler syndrome is an AD disorder caused by mutations in COL2A1 (12q13), COL11A1 (1p21), COL11A2 (6p21)
CF of Stickler syndrome
- 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
CF of 22q11.2 Deletion Syndrome
- Cardiac abnormalities
- Abnormal facies
- Thymic hypoplasia
- Cleft palate
- Hypocalcaemia
mnemonic : CATCH-22
———— 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
Association
* these anomalies are idopathic
CF of VACTERL association syndrome
- Vertebral
- Anorectal
- Cardiac
- Tracheo-
- Esophageal
- Renal
- Limb
***
CF of CHARGE syndrome
- Coloboma
- Heart defects
- Atresia (choanal)
- Retardation of growth and development
- Genital anomalies
- Ear anomalies
CHARGE syndrome is due to ——- mutatios
heterozygous CHD7
