genetics-clark-dysmorphology
Terms
undefined, object
copy deck
- what percentage of babies who die has a congenital birth defect
- ~33%, 1/3
- Trisomy 13 phenotype (give 3)
- Cleft lip, extra toe, extra finger, mass at base of ambililicus w/ loops, infalacele, small falus, small eyes, broad nose , scalp defect
- majority of birth defects are known T/F
- F (unknown
-
1)give 2 extrinsic factors of abnormal morphogenesis
2)relative recurrance risk? -
1)Deformation
Disruption
2) low - 1)give an intrinsic factor of abnormal morphogenesis
-
1) Malformation
2)higher recurrence risk - Deformation
-
Anomaly caused by an abnormal mechanical force that alters the shape of, but does not destroy, an otherwise normal organ without halting morphogenesis
e.g., papoose -
Deformation
give 2 classes
give examples -
1)The presence of an abnormal force
- Dislocated hip from breech presentation
- Torticollis and craniofacial asymmetry from entrapment in a bifid uterus
- Facial compression and pulmonary hypoplasia from oligohydramnios (insufficient amniotic fluid)
- Intrauterine constraint in large for gestational age babies and multiple gestations
-transverse lie
2) The absence of a normal mechanical force
- High arched palate in myotonic dystrophy - Potter sequence
-
Renal agenesis
Oligohydramnios
Pulmonary hypoplasia
In utero constraint
Genu recurvatum
Rocker bottom feet
Large flat ears - Oligohydramnios
- Consequences of Insufficient amniotic fluid
- Disruption
- Anomaly caused by an environmental or extrinsic factor that destroys otherwise normal tissue and interrupts normal morphogenesis
- teratogen
- A drug or other agent that causes abnormal prenatal development.
- give 2 major causes of disruption
-
1)exposure to teratogens
e.g. retinoic acid, thalidomide, etoh, tobacco
2)absence of morphogen
e.g., folic acid - give 2 examples of disruption
-
Microcephaly from maternal PKU
Cataract, deafness, heart defect and mental retardation from rubella
Limb anomalies from thalidomide
Ear and brain anomalies from retinoic acid
Amputations and constriction rings due to amniotic bands - Retinoic acid embryopathy
-
Increased risk of miscarriage
Ear anomalies
Facial palsy
Aortic arch anomalies - Other causes of disruption
-
Other Causes:
Maternal Disease
- Diabetes
- Phenylketonuria (PKU)
Maternal Infection
- Rubella
- Cytomegalovirus
Vascular accidents
- Hypotension, placental
- hemorrhage/abruption
- Thromboemboli
Amniotic Rupture - Amniotic Band Sequence
-
Asymmetric amputations
Circumferetial constrictions bands
Distal swelling
Normal anatomy proximal to lesions
Distal and proximal amputations
Low recurrence risk - Vascular disruption Amyoplasia
-
Hypoxia or hypoperfusion of cord
Diminished muscle mass
Policeman’s tip position of arm - Amyoplasia and Amniotic bands
-
Amniotic rupture at time of vascular event
Decreased movement may prevent serious amputations - women of reproductive age should take how much folic acid daily
- 400mcg
- Malformation (def)
-
Definition
Anomaly caused by intrinsic factors that result in abnormal tissue or defective morphogenesis - Malformation - Neural tube defect
-
Failed closure of neural tube at 28 days gestation
Multifactorial trait
3% recurrence risk
Folic acid can prevent 70% when taken prior to conception - Malformation - Ectrodactyly
-
Split hand and foot with absent middle rays
Inherited as an autosomal dominant trait
Can occur in isolation or as part of syndromes - Malformation – Cleft lip/Palate
-
Failure of premaxilla to fuse with lateral facial processes at 7 weeks gestation
Usually inherited as a multifactorial trait
Can occur in isolation or as part of syndromes - When there is more than one anomaly, the _______ between the anomalies is the key to the diagnosis
- relationship
- Syndrome (def.)
- A recognizable pattern of anomalies with a single cause
- Van der Woude syndrome - clinical signs
- -characterized by left palate, Cleft lip, Lip pits
-
Van der Woude syndrome -
genotype -
Autosomal dominant trait
IRF6 gene mutation detectable in 50%
Variable expressivity and penetrance
70% who inherit the mutation have a cleft that requires surgery -
EEC Syndrome
clinical signs & genotype -
Ectrodactyly
Ectodermal dysplasia
Cleft lip and palate
Autosomal dominant disorder - Adams Oliver syndrome
-
Autosomal dominant trait
Transverse terminal defect - Ectrodactyly
Scalp and skin defects
Symmetric lesions
Autosomal dominant trait with variable expressivity
Check parents for small scalp defect
Can be mistaken for amniotic band sequence, but symmetry of lesions rules that out. - Dysplasia (def)
- A pattern of malformations affecting the same tissue type.
- X-linked Ectodermal Dysplasia
-
Females can be mildly affected with thin hair, poor teeth and patchy sweating
Males have missing or needle-like teeth, absent sweating, dry skin, alopecia - Achondroplasia
-
Most common bone dysplasia
Autosomal dominant disorder
Mutations in FGFR3 exclusively of paternal origin
Advanced paternal age is common; most are new mutations
Different FGFR3 mutations cause similar disorders: hypochondroplasia and thanatophoric dysplasia - Thanatophoric Dysplasia
-
Most common lethal bone dysplasia
Rhizomelia-shortening of upper long bones
Trident hand - Thanatophoric dysplasia Radiographic features
-
Telephone receiver femurs
Stellate iliac bones - Osteogenesis Imperfecta, Type II
-
Lethal defect of collagen
Severe intrauterine fractures
Autosomal dominant trait
Most are new mutations
Parental gonadal mosaicism leads to recurrence in 2-6% - Osteogenesis Imperfecta, II Radiographic features
-
Accordion femur
Beaded ribs
Bent long bones Multiple fractures - Association (def.)
-
Definition
A pattern on anomalies that occur together more often than expected by chance alone, but not in any single pattern and not necessarily with a single cause. - example of Association
-
Example:
In VATER association the following anomalies occur together more commonly than would be predicted by chance yet in no particular pattern
-VSD and Vertebral defects
-Imperforate anus
-Tracheo-esophageal fistula
-Radial and Renal defects - Sequence (def.)
-
Definition
A pattern of anomalies in which a primary defect leads to one or more secondary defects; a cascade effect - Holoprosencephaly Sequence
-
- Midline CNS structures induce premaxillary process
- Premaxillary agenesis - Holoprosencephaly Sequence “The face predicts the brainâ€
-
Cebocephaly, single nostril
Check parents for single central incisor