Developmental Disorders - Lecture 19 Flashcards
Malformations
Primary errors of morphogenesis, are usually multifactorial, involving a number of etiological agents including genetic and enviromental factors
Disruptions
Distrurbances in otherwise normal morphogenetic processes, example: amnionic band
Deformations
Disturbances in otherwise normal morphogenic processes caused by abnormal biomechanical forces like uterine constraints. Clubfoot is an example
Sequences
A series of events triggered by one initiation factor.
Example: oligohydroamnios - decresed amniotic fluid - which leads to a variety of events like fetal compression and problems that stem from that
Syndromes
Syndromes are constellations of congenital anomalies that are thought to be pathologically related but cannot be explained on the basis of a single local intial event
Ie viral infection
Critical period
A window of time in develop where the developing organism is susceptible to insult or development problems
Causes of congenital anomalies
Unknown - 50%
Multifactorial - 25%
Environmental - 7%
Genetic - chromosomal 10%, monogenic 8%
Gene mutation
Include inborn errors of metabolism - rare
Most commonly autosomal recessive or x-linked
Often effect enzymes and biochemical pathways
Examples: phenylketonuria
Galactosemia
Cystic fibrosis
Chromosomal genetic factors
Rearrangements - deletions, duplicatiions, inversiions, translocations
Aneuploidy
- changes in chromosome number (not 2N)
- trisomy 21, trisomy 13, turner syndrome, poly-X syndrome
Euplody
Addtion of a complete set of chromosomes
Retention of polar body or fertilization by moroe than one sperm
Early spontaneous abortion
What are some infectious agents that can cause birth abnormalities?
Viral infections - rubella, CMV, HSV, Varicella-zoster, flu, mumps, bacterial and protzoans
radiation
Maternal diabeties
Thalidomide
Alcohol
Retinoic acid
Folic Acid
What are the effects of thalidomide, alcohol, retinoic acids and folic acid on birth abnormalities?
Retinoic acid - defects mostly related to the neural crest, so facial structures, outflow track of the heart and the thymus.
thalidomine - extreme limb malformation, cardiovascular malformation, no ears, urinary system, GI and facial defects
alcohol - fetal alcohol syndrome
folic acid - anencephaly, growth retardation, cleft lip and palate, hydrocephaly, hypoplastic mandible and low-set ears.
What are the effects of radiation or maternal diabetes on birth abnormalilties?
Radiation - predominately CNS defects from spina bifida to mental retardation but also cleft palate, microcephaly, malformation of the viscera, limbs and skeleton
Diabetes - high birth weight and stillborns
Dysplasia
An abnormality caused by mechanical forces
-amnionic band constriction
Association
A group of anomalies seen in more than one individual that cannot yet be attributed to a definitive cause
What is teratology? What is a teratogen?
Teratology literally means “study of monsters”, clinically its the study of congenital malformations
A teratogen is an enviromental agent that causes birth defects
Gene mutations associated with birth abnormalities
include inborn errors of metabolism
- mostly autosomal recessive or x-linked
- affect enzymes and biochemical pathways
examples:
- phenylketonuria: accumulation of phenylalanine
- galactosemia: tissue accumulation of galactose 1-phosphate
-cystic fibrosis: CFTR chlorine transporter mutation
what are chromosome rearrangements? and examples
deletions, duplications, inversions, translocations
ex - cri du chat syndrome - mentally retarded and microcephaly
aneuploidy
changes in chromosome number beyond the 2N state includes: trisomy 21 trisomy 13 turner syndrome poly-X syndrome
Turner Syndrome
X0 - only one X chromosome, 45 total
characteristics:
female with underdeveloped sex characteristics, low hairline, broad chest, folds on neck, usually sterile and usually of normal intelligence
Poly-X Syndrome
XXX
usually tall and thin, often fertile and most have normal intelligence
what are example of infectious agents that cause birth abnormalities?
Rubella virus cytomegalovirus treponema toxoplasmosis zika virus herpes simplex varicella-zoster flu mumps
Causes and symptoms of neonatal respiratory distress syndrome
immaturity of the lungs, in premature birth, lack of pulmonary surfactant. Pulmonary surfactant makes inspiring easier
Causes and symptoms of hydrops
accumulation of edema fluid in the fetus. common cause is blood group incompatibility between mother and fetus - immune hydrops
mother Rh-, baby Rh+
Nonimmune hydrops - causes: cardiovascular defects such as congenital cardiac defects and arrhythmias, chromosomal anomalies and kernicturus
