Unit 7 - Birth Defects Flashcards
(35 cards)
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:
- NTD
- cleft lip/palate
- Down
- 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?
1: 150
- 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?
- 13q
- del(18p)
- del(7)(q36)
- dup(3)(p24-pter)
- del(2)(p21)
- 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
- microcephaly
- patent ductus arteriosus
- cataracts
what effects do the following have on birth?
- Coxsackie B virus
- Toxoplasmosis
- hyperthermia
- increased spontaneous abortion
- cerebral calcifications and head defects
- 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?
- genotype of embryo (gene-environmental factors) and mother (determine drug metabolism, resistance to infection, etc.)
- developmental stage at time of exposure (most sensitive period is weeks 3-8 during embryogenesis)
- 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?
- learning/remembering
- understanding and following direcctions
- controlling emotions
- communicating and socializing
- daily life skills (feeding, bathing)
what is included in FASD?
- ARBD (alcohol-related birth defects)
- ARND (alcohol-related neurodevelopmental disorder)
- PFAS (parietal fetal alcohol syndrome)
- 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?
- cell migration and adhesion
- cell proliferation and survival
- 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)
