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Flashcards in Unit 7 - Birth Defects Deck (35)
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what are the leading causes of infant mortality?

premature birth and birth defects


how many embryos spontaneously abort? how many are live-born with birth defects?

50% of embryos spontaneously abort

3-6% are born with birth defects


what are congenital malformations?

birth defects that are structural, behavioral, functional, or metabolic, and present at birth
-occur in 3% of live births (1:33), and account for 25% of deaths


per 1000 births, how many are:
-cleft lip/palate
-cerebral palsy
-heart defects

<1 NTD
1 cleft
1.25 Down
3.1 cerebral palsy
5-10 CHDs (critical for life, very susceptible to errors)


what are the known causes of birth defects?

-genetic problems (28%); Xm abnormalities or gene mutations
-environmental factors (3-4%)
-gene + environment (20-25%)
-twinning (~1%); usually if conjoined
-unknown (40-45%)


genetics of birth defects

-can be due to single gene mutations
-can be due to Xmal abnormalities
-often sporadic
-can be inherited as dominant, recessive, or X-linked


how many babies are born with defects caused by errors in number or structure of Xm? how do they come about?

-inherited or de novo


what is Axenfield-Rieger syndrome? its symptoms?

a multi-system disorder that primarily affects eyes
-hypertelorism (widely spaced eyes)
-flattened mid-face with broad, nasal bridge
-prominent forehead
-microdontia or oligodontia
-redundant periumbilical skin


what is the prevelence of Axenfield-Rieger syndrome? its inheritance? its cause?

1:200,000 in autosomal dominant pattern
-caused by mutations in at least PITX2 and FOXC1
--code for transcription factors in developing eye (anterior segment) and other body parts


what is the prevalence of holoproencephaly in embryos VS live-born infants? what are some causes?

1:250 embryos, and 1:10,000 live-born
-caused by Xmal abnormality (25-50%); numerical trisomy 13, 18, and structural
--18-25% are due to mutation in single gene
-environmental factors (maternal diabetes)


what is holoproencephaly?

structural anomaly of brain resulting from failed/incomplete forebrain division in 3rd and 4th weeks of gestation
-forebrain incompletely cleaves, causing defects in face and brain development


what are the most frequent deletions/duplications causing HPE?

1. 13q
2. del(18p)
3. del(7)(q36)
4. dup(3)(p24-pter)
5. del(2)(p21)
6. del(21)(q22.3)


what is the msot common environmental factor known to cause HPE?

maternal diabetes and recently statins
-alcohol and retinoic acid in animals


what are key genes implicated in HPE?

genes that operate on SHH (PTCH, GLI, DUSP)


what was the first linkage of infectious agents to birth defects?

rubella viral infections during pregnancy = congenital rubella syndrome
-patent ductus arteriosus


what effects do the following have on birth?
1. Coxsackie B virus
2. Toxoplasmosis
3. hyperthermia

1. increased spontaneous abortion
2. cerebral calcifications and head defects
3. disrupted neurulation and NTDs (from fever)


birth defects associated with thalidomide and when

day 35-37: absence of ears and deafness
39-41: absence of arms
43-44: phocomelia with 3 fingers
46-48: thumbs with three joints


what factors does susceptibility to teratogens depend on?

1. genotype of embryo (gene-environmental factors) and mother (determine drug metabolism, resistance to infection, etc.)
2. developmental stage at time of exposure (most sensitive period is weeks 3-8 during embryogenesis)
3. dose and duration of exposure


difference between fetal alcohol syndrome and fetal alcohol spectrum disorder

FASD refers to all alcohol-related defects (amount, timing, and genetics all contribute)
-FAS is most severe form on the spectrum


what developmental problems can alcohol-affected fetuses have?

-understanding and following direcctions
-controlling emotions
-communicating and socializing
-daily life skills (feeding, bathing)


what is included in FASD?

1. ARBD (alcohol-related birth defects)
2. ARND (alcohol-related neurodevelopmental disorder)
3. PFAS (parietal fetal alcohol syndrome)
4. FAS (most severe)


what structural defects are involved with FAS?

-small head
-epicanthal folds
-flat midface
-smooth philtrum
-low nasal bridge
-small eye openings
-short nose
-thin upper lip
-dramatically smaller brain


what are the proposed mechanisms of alcohol interference with embryo development?

1. cell migration and adhesion
2. cell proliferation and survival
3. cell signaling and gene expression

cause exencephaly and nose/lip defects


what is the most common birth defect?

malformation of the heart (1% of life briths, 10% of fetuses)


what are the causes of congenital heart defects?

majority are multifactorial (gene-environment interactions)
-12% Xmal abmormality
-2% environmental teratogens


what percentage of CHDs are atrial VS ventricular septal defects?

ASD: 10% of all CHD
VSD: 20% of all CHD (2-6 of every 1000 live births)


what is dextrocardia? when does it cause problems?

heart is positioned on right side of thorax instead of left
-caused by defects in establishing left-right body axis
-if heterotaxy, can cause septal defects, double outlet right ventricle (DORV), and transposition of great arteries (TGA)


what is DORV?

double outlet right ventricle
-aorta arises from right ventricle, with pulmonary artery (left ventricle doesn't provide anything)
-always includes VSD to help infant


what is TGA?

transposition of great arteries
-main pulmonary artery and aorta are switched in position
-often have septal defects to allow blood mixing


what are signs and symptoms of severe heart defects in newborns?

-rapid breathing
-poor blood circulation

many aren't diagnosed until children are older


22q11.2 deletion syndrome presentation

1:4000 heterogenous multisystem syndrome
-3 million bp deletion (30-40 genes)
-5-10% of cases are inherited (AD)
-80% have CHD
--teratology of Fallot and truncus arteriosus
-palate defects
-mental retardation
-mild differences inf acial features


what gives rise to the great arteries/

outflow tract of embryonic heart


what happens in babies with truncus arteriosus?

aorta and pulmonary artery fail to separate completely, and usually associated with VSD
-O2-poor and O-rich blood are mixed as blood flows to both lungs and rest of body
-single common truncal valve controlling flow, and usually abnormal
--valve can be thickened and narrowed (blocks blood when it leaves) or leaky (goes back into heart)


Tetralogy of Fallot problems

1. VSD
2. pulmonary stenosis
3. overriding aorta (increases flow)
4. ventricular hypertrophy


how do cardiac neural crest cells contribute to outflow tract?

Tbx1 --> Fgf8 --> CNCC deployment
-these genes are located in the 22q11.2 deletion region

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