Dysmorphology- Clark Flashcards
What are the major causes/etiologies and mechanisms responsible for congenital anomalies?
Congenital anomalies
•Leading cause of death in term newborns (33%).
•Major causes:
•Known (40%)
oMultifactorial disorders (20%)
oSingle gene disorders (8%)
oEnvironmental agents (6%)
oChromosome anomalies (6%)
•Unknown (60%)
oAbnormal morphogenesis is due to:
•Extrinsic factors: deformation, disruption.
•Have lower recurrence risk.
•Intrinsic factors: malformation
•Higher recurrence risk.
Define deformation and provide some examples. How are deformations due to extrinsic factors? How does a breach position or a transverse lie lead to deformation?
Definition: anomaly caused by an abnormal mechanical force that alters the shape of, but does not destroy, an otherwise normal organ w/o halting morphogenesis.
Examples:
•The presence of an abnormal force
o Dislocated hip from breech presentation.
o Breech presentation due to uterine sacculation (softening in wall of uterus).
o Torticollis and craniofacial asymmetry from entrapment in a bifid uterus.
o Facial compression and pulmonary hypoplasia from oligohydramnios (insufficient amniotic fluid).
•Oligohydramnios presents w/ potter sequence.
o Intrauterine constraint in large gestational age babies and multiple gestations (twins).
•The absence of a normal mechanical force
o High arched palate in myotonic dystrophy
Define disruption and provide some examples. What are some causes of disruptions? What is the amniotic band sequence?
Definition: anomaly caused by an environmental or extrinsic factor that destroys otherwise normal tissue and interrupts normal morphogenesis.
•Causes: teratogens
•Amyoplasia w/ amniotic band:
• Hypoperfusion/hypoxia of cord.
• Decreased fetal movement. (may help prevent amputations)
• Results in policeman’s tip.
• Asymmetric amputations.
• Circumferential constriction bands.
• Distal swelling.
• Normal anatomy proximal to lesions.
• Distal and proximal amputations.
How do teratogens lead to disruptions?
Teratogens: Retinoic Acid - Accutane (acne treatment) •Absence of external auditory canal •Ear, aortic arch, brain defects, SAb Thalidomide •Limb defects, phocomelia •Used in leprosy, rheumatoid arthritis Tobacco •Growth retardation, miscarriage Alcohol - Fetal Alcohol Syndrome •Fetal alcohol spectrum affects up to 1% of population in US •Poor growth, microcephaly •Mental retardation, short palpebral fissures, smooth philtrum, thin upper lip, “railroad track ears” (helix and antihelix mirror each other). •Heart defect, Cleft lip
What are morphogens? What is the role of folic acid supplementation in reducing birth defects? What are the current CDC guidelines for folic acid supplementation for all women of reproductive age? What are the current CDC guidelines for folic acid supplementation for women that have had a child with spina bifida or anencephaly?
Morphogen: a factor required for normal morphogenesis.
Folic acid: a water soluble B vitamin: Vitamin B9
•Deficiency results in neural tube defects, cleft lip and cardiac anomalies.
•Supplementation with folic acid reduces the incidence of many birth defects, including neural tube defects and diabetic embryopathy.
•The CDC recommends that all women of reproductive age take a folic acid supplement of 400 micrograms, daily.
•After the birth of a child with spina bifida or anencephaly, a woman should take 4 milligrams daily to reduce the chance of a neural tube defect in the next pregnancy.
Define malformation and provide some examples of isolated malformations (2) and of malformation syndromes (2).
Definition: anomaly caused by intrinsic factors that result in abnormal tissue or defective morphogenesis.
1. Adams Oliver syndrome:
•Autosomal dominant trait variable expression and incomplete penetrance.
•Has symmetrical lesions.
2. Isolated Neural tube defect
•Failure to close neural tube at 28 days.
•Prevented by taking folic acid.
3. Isolated cleft lip/palate
•Failure of premaxilla to fuse w/ lateral facial processes.
•Usually inherited as a multifactorial trait.
4. Van der Woude syndrome
•Autosomal dominant trait
•Single gene disorder.
•Can result in lip pits too.
Define syndrome and provide some examples (5).
Syndrome: a recognizable pattern of anomalies w/ a single cause.
1. Aarskog syndrome:
•Shawl scrotum, short stature, mild webbing, anteverted nares.
2. Cornelia de Lange syndrome:
•Cohesin complex defects – proteins play a role in sister chromatic cohesion.
3. Kabuki syndrome:
4. Angelman syndrome:
•Deletion in maternally derived chromosome 15q11.2
5. Rett syndrome
•X-linked trait seen almost solely in female.
•Lack of purposeful use of the hand.
Define dysplasia and provide some examples (2).
Dysplasia: a pattern of malformations affecting the same tissue type.
1. X-linked ectodermal dysplasia
•Females can be mildly affected w/ thin hair, poor teeth and patchy sweating.
•Males have missing or needle-like teeth, absent sweating, dry skin, alopecia.
2. Skeletal dysplasia:
•Achondroplasia
oMost common
oMutations from paternal parent.
oAdvanced paternal age.
•Lethal: Thanatophoric and osteogenesis imperfecta type II
Define association and provide some examples (1).
Association: a pattern of anomalies that occur together more often than expected by chance alone, but not in any single pattern and not necessarily w/ a single cause.
1. VATER association
•VSD and Vertebral defects, Imperforate Anus, Tracheo-Esophageal fistula, Radial and Renal defects.
Define sequence. What is the holoprosencephaly sequence? What are some causes of the holoprosencephaly sequence and what are some microforms present in the parents?
Sequence: a pattern of anomalies in which a primary defect leads to one or more secondary defects; a cascade effect.
Holoprosencephaly:Failure of cleavage of cranial hemispheres: lobar, semilobar and alobar.
•Sequence: the face predicts the brain.
o Lack of Cupid’s bow.
o Lack of midline frenulum.
o Single central incisor on brain MRI
o Deletion of Sonic hedgehog (SHH) gene detected by array CGH.
o Cebocephaly = single nostril
•Causes: Can be due to chromosome anomalies (41%), microdeletions (8.5%) or mutations (14%).
•Maternal diabetes strongly associated w/ HPE.
•Microforms present in parents: hypotelorism, ansomia, single incisor, and microcephaly.
