Developmental Disorders: Causes, Mechanisms and Patterns

Question 1

teratology and teratogens

Answer 1

teratology: the study of monsters; study of congenital malformations
teratogens: agents that produce birth defects

Question 2

phocomelia

Answer 2

hands and feet seem to arise almost directly from the shoulder and the hip

Question 3

amelia

Answer 3

limb is entirely missing; caused once by thalidomide

Question 4

statistics on teratology

Answer 4

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

Question 5

factors that increase incidence of congenital malformations

Answer 5

1. parental age (maternal age: down syndrome; paternal age: achondroplasia, Alpert’s syndrome)
2. season of the year (nutritional deficiencies); anencephaly occurs more frequently in January
3. country of residence: environmental, political factors
4. race: cleft palate 1 for AA, 2x for Caucasians, 4x for Orientals
5. familial tendencies: extra digits in Amish communities

Question 6

susceptibility of embryo to teratogens

Answer 6

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

Question 7

polyploidy

Answer 7

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

Question 8

monosomy

Answer 8

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

Question 9

trisomy

Answer 9

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

Question 10

abnormal chromosome structure

Answer 10

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

Question 11

genetic mutations

Answer 11

expressed as morphological abnormalities; can be dominant or recessive

dominant: aniridia (lack of iris), polycystic kidney disease) recessive (albinism, cystic fibrosis, PKU)

Question 12

Environmental Factors: Maternal Infections

Answer 12

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

Question 13

folic acid antagonists

Answer 13

highly embryolethal; used as abortifacients

example: aminopterin (produces multiple severe anomalies such as anencephaly, growth retardation, cleft lip and palate, hydrocephaly, hypoplastic mandible)

Question 14

androgenic hormones

Answer 14

female births with various degrees of masculinization of the external genitalia

Question 15

anticonvulsants

Answer 15

phenytoin produces fetal hydantoin syndrome of anomalies including growth anomalies, craniofacial defects, nail and digital hypoplasia, mental retardation

Question 16

sedatives and tranquilizers

Answer 16

thalidomide is highly teratogenic; gross malformation of limbs, malformations of cardiovascular system,

Question 17

antineoplastic agents

Answer 17

severe organ malformations

Question 18

alcohol

Answer 18

poor postnatal growth rate, microcephaly, mental retardation, heart defects, hypoplasia of facial structures

Question 19

retinoic acid (vitamin A)

Answer 19

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

Question 20

antibiotics

Answer 20

streptomycin: deafness
tetracycline: discoloration of teeth and bones, can interfere with enamel formation

Question 21

ionizing radiation

Answer 21

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)

Question 22

temperature extremes

Answer 22

can cause teratogenic effects

Question 23

excess concentration of oxygen

Answer 23

retrolental fibroplasia

Question 24

maternal diabetes

Answer 24

high birth weight; stillbirths; increased risk for structural anomalies

Question 25

nutrition of mother

Answer 25

severely deficient in iodine, cretinism (growth retardation, mental retardation, short and broad hands, short fingers, dry skin, difficulty breathing)

Question 26

smoking

Answer 26

low birth weight and low rate of growth after birth

Question 27

mechanical factors: abnormal intrauterine pressure

Answer 27

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

Question 28

developmental disturbances: duplications and reversal of asymmetry

Answer 28

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

Question 29

DD: faulty inductive tissue interactions

Answer 29

absent or faulty inductions; absence of lens (aphakia) or of kidney (renal agenesis)

Question 30

DD: absence of normal cell death

Answer 30

syndactyly (webbed digits); atavism (persistence of phylogenetically primitive structures like tail)

Question 31

DD: failure of tube formation

Answer 31

spina bifida: incomplete fusion of neural tube

Question 32

DD: disturbances in tissue resorption

Answer 32

anal atresia: never develop anus

Question 33

DD: failure of migration

Answer 33

pelvic or horseshoe kidneys

cryptorchidism (failure of testicles to descend)

Question 34

DD: developmental arrest

Answer 34

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

Question 35

DD: destruction of formed structures

Answer 35

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

Question 36

DD: failure to fuse or merge

Answer 36

results in malformations of lower face;

Question 37

DD: hypoplasia or hyperplasia

Answer 37

hypoplastic structure is too small, hyperplastic structure is too large; incorrect amount of tissue produced

Question 38

DD: receptor defects

Answer 38

testicular feminization syndrome: lack of testosterone receptors results in development of a typical female phenotype in a genetic male

Question 39

DD: defective field

Answer 39

boundary disturbances; sirenomelia: fusion of lower limb fields; extreme example of caudal regression syndrome resulting from abnormal T gene function

Question 40

DD: secondary signaling defects

Answer 40

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

Question 41

DD: germ layer defects

Answer 41

ectodermal dysplasia includes a wide variety of anomalies from hair, teeth, skin, nails, neurological defects