Developmental Disorders: Causes, Mechanisms and Patterns Flashcards
teratology and teratogens
teratology: the study of monsters; study of congenital malformations
teratogens: agents that produce birth defects
phocomelia
hands and feet seem to arise almost directly from the shoulder and the hip
amelia
limb is entirely missing; caused once by thalidomide
statistics on teratology
2-3% of newborns 4-6% children (defects noted later) 20% cause stillbirth 30% of infants admitted to pediatric units 50% of defects have no known cause
factors that increase incidence of congenital malformations
- parental age (maternal age: down syndrome; paternal age: achondroplasia, Alpert’s syndrome)
- season of the year (nutritional deficiencies); anencephaly occurs more frequently in January
- country of residence: environmental, political factors
- race: cleft palate 1 for AA, 2x for Caucasians, 4x for Orientals
- familial tendencies: extra digits in Amish communities
susceptibility of embryo to teratogens
weeks 1-3: low; will either kill the embryo or are compensated for by the powerful regulatory properties of the early embryo
maximal susceptibility: weeks 3-8: period when most of the major organs and body regions are first being established
anomalies arising from 3-9th month tend to be functional or involve disturbances in the growth of already formed body parts
different organs have different periods of susceptibility during embryogenesis
polyploidy
chromosomal number is higher multiples than 2 of the haploid number of chromosomes
most cases abort spontaneously
seems to be caused by either polyspermy or lack of separation of polar body during meiosis
monosomy
lack of one member of a chromosome pair; result of nondisjunction
most embryos re not viable;
Turner’s syndrome: female phenotype but the gonads are sterile
trisomy
triplet instead of the normal chromosome pair; result of nondisjunction
Trisomy 21: Down syndrome; mmentally retarded and have characteristic broad face with flat nasal bridge; heart defects;
trisomy of chromosomes 13 and 18: severely malformed fetuses man yof which do not survive to birth; severe mental retardation and other defects of CNS; cleft lip and cleft palate; polydactyly (t13) and rocker bottom feet
abnormal chromosome structure
reciprocal translocations: recombination between 2 nonhomologous chromosomes
isochrome formation: two daughter chromosomes are formed, each lacking one chromosome arm but with the other arm doubled
deletions and duplications
cri du chat syndrome: deletion of short arm of chromosome 5; craniofacial abnormalities, windpipe abnormalities learning disabilities
genetic mutations
expressed as morphological abnormalities; can be dominant or recessive
dominant: aniridia (lack of iris), polycystic kidney disease) recessive (albinism, cystic fibrosis, PKU)
Environmental Factors: Maternal Infections
may interfere with formation or destroy formed structures
most caused by viruses: rubella (cataracts, deafness, cardiovascular defects, fetal growth retardation),, cytomegalovirus (microcephaly, microphthalmia, cerebral calcification, intrauterine growth retardation)
toxoplasma gondii (protozoan)–microcephaly, hydrocephaly, cerebral calcification, microphthalmia, mental retardation, prematurity
spirochete treponema pallidum (syphilis)–dental anomalies, deafness, mental retardation, skin and bone lesions, meningitis
folic acid antagonists
highly embryolethal; used as abortifacients
example: aminopterin (produces multiple severe anomalies such as anencephaly, growth retardation, cleft lip and palate, hydrocephaly, hypoplastic mandible)
androgenic hormones
female births with various degrees of masculinization of the external genitalia
anticonvulsants
phenytoin produces fetal hydantoin syndrome of anomalies including growth anomalies, craniofacial defects, nail and digital hypoplasia, mental retardation
sedatives and tranquilizers
thalidomide is highly teratogenic; gross malformation of limbs, malformations of cardiovascular system,
antineoplastic agents
severe organ malformations
alcohol
poor postnatal growth rate, microcephaly, mental retardation, heart defects, hypoplasia of facial structures
retinoic acid (vitamin A)
malformation of neural crest derivatives; variety of facial structures, outflow tract of heart, thymus
retinoic acid affects Hox genes, especially with genes in cranial and pharyngeal region
antibiotics
streptomycin: deafness
tetracycline: discoloration of teeth and bones, can interfere with enamel formation
ionizing radiation
response is dependent on dose and related to the stage at which the embryo is irradiated
can produce breaks in DNA and known to cause mutations ; defects of CNS (spina bifida to mental retardation)
temperature extremes
can cause teratogenic effects
excess concentration of oxygen
retrolental fibroplasia
maternal diabetes
high birth weight; stillbirths; increased risk for structural anomalies
nutrition of mother
severely deficient in iodine, cretinism (growth retardation, mental retardation, short and broad hands, short fingers, dry skin, difficulty breathing)
smoking
low birth weight and low rate of growth after birth
mechanical factors: abnormal intrauterine pressure
oligohydramnios: reduced amount of amniotic fluid causing club foot, congenital hip dislocations, skull deformation
amniotic bands constricting digits or extremities of fetus cause intrauterine amputations; form as result of tears to the extraembryonic membranes during pregnancy
developmental disturbances: duplications and reversal of asymmetry
twinning; conjoined twins are a problem ; can be joined at any site to any degree; parasitic twinning (one member of twin is relatively normal, but the other is represented by a much smaller body, often consisting of just the torso and limbs attached to an area such as the mouth or lower abdomen of the host twin)
situs inversus: complete reversal of asymmetry of internal organs
DD: faulty inductive tissue interactions
absent or faulty inductions; absence of lens (aphakia) or of kidney (renal agenesis)
DD: absence of normal cell death
syndactyly (webbed digits); atavism (persistence of phylogenetically primitive structures like tail)
DD: failure of tube formation
spina bifida: incomplete fusion of neural tube
DD: disturbances in tissue resorption
anal atresia: never develop anus
DD: failure of migration
pelvic or horseshoe kidneys
cryptorchidism (failure of testicles to descend)
DD: developmental arrest
cleft palate and cleft lip; thyroglossal duct: persisting epithelial cells mark the path of the thyroid glad as it migrate from the base of the tongue to its normal position
DD: destruction of formed structures
if structure is in the early primordial stage, any tissues to which the primordium would normally give rise are missing or malformed
phocomelia: damage to proximal blood vessels destroy primordia of proximal limb segments
DD: failure to fuse or merge
results in malformations of lower face;
DD: hypoplasia or hyperplasia
hypoplastic structure is too small, hyperplastic structure is too large; incorrect amount of tissue produced
DD: receptor defects
testicular feminization syndrome: lack of testosterone receptors results in development of a typical female phenotype in a genetic male
DD: defective field
boundary disturbances; sirenomelia: fusion of lower limb fields; extreme example of caudal regression syndrome resulting from abnormal T gene function
DD: secondary signaling defects
loss of one structure has a domino effect ; cyclopia primary defect is deficiency of forebrain tissue that results from deficient shh signaling; facial defects secondary to this
DD: germ layer defects
ectodermal dysplasia includes a wide variety of anomalies from hair, teeth, skin, nails, neurological defects
