(1-20-15)
Categories of biological contribution to phenotypical development (Cattell, 1950)
- Hereditary-direct parental contribution
- Innate-mutation and segregation of genetic material
- Congenital-acquired in uterus; occurring between conception and completion of the birth process
- prenatal effects: acquired in uterus
- natal effects: associated with the birth process
- Constitutional-alteration of body by life experience
Hereditary Influences: Mechanisms of Genetic Transmission
- Biological foundation
- chromosome, genes, alleles, DNA
- karyotype: arrangement of chromosomes in standard order
- mitosis: common cell reproduction
- meiosis: cell division from germ cells (46 chromosomes) to gametes (sex cells) (23 chromosomes)
- Classical genetic principles: Gregor Mendel, 1866
- dominant and recessive characteristics: relationships between genes
- phenotype, genotype
- Exceptions to Mendelian Inheritance
- additivity: blood type
- polygenetic inheritance: height, neural tube defects, possibly aspects of intelligence
- imprinting
- Angelman Syndrome and Prader-Willi Syndrome usually arise from deletion of genetic material from a site on chromsome 15 (15q11-13). If the deletion occurs on the chromosome 15 inherited from the mother Angelman syndrome results, if from the c15 passed from the father Prader-Willi syndrome results.
- Seeming exceptions to Mendelian inheritance: sex-linked characteristics
- Autosomes and Sex Chromosomes
- X-linked characteristics
- Hemophilia
- Red-green color blindness
- Baldness
- Some forms of muscular dystrophy, anemia, albinism
- X chromosome inactivation in females
Hereditary Influences
Recessive gene disorders (1000+ catalogued)
- Phenylketonuria (PKU)
- one of over 23 Overflow Aminocidurias
- Gene for human phenylalanine hydroxylase is on chromosome 12.
- gene incidence app. 1 in 100
- occurrence app. 1 in 10,000 to 15,0000 live births
- IQ usually below 50, often below 20
- Disturbance in pigment formation yields affected children with fair, lightly pigmented skin, blond hair, and blue eyes. A “sweet” or “mousy” (animal-like) odor is reported. No specific dysmorphic features. App. 25% major motor seizures.
- treatment by 65 days, mean IQ 93+16
- treatment 1st month: 95
- treatment 2nd month: 85
- Termination of diet is followed by neuropsychological and behavior problems.
- It is especially important that women with PKU return to a diet before becoming pregnant to decrease risks of congenital abnormalities and mental retardation in children exposed prenatally to high levels of maternal phenylalanine.
- Glactosemia
- inborn error carbohydrate metabolism
- app. 1 in 62,000 live births
- Clinical expression is variable: untreated infants may die of liver and kidney failure, some degree of mental retardation was common, vision impairments due to cataracts.
- With careful dietary management, intellectual functioning is usually found to be in the normal range; speech, language, and visuospatial deficits may still be over represented.
- Tay-Sachs Disease (Amaurotic Family Idiocy)
- one of a number of recessive lipid diseases characterized by a regressive course
- Family Microcephalus
- anomaly of cranial formation: sever MR
- Hypothyroidism (Inherited Cretinism)
- absence, insufficiency, or error in production of thyroid hormone
1-22-15
Dominant Gene Disorders (1200+ catalogued)
- Tuberous Sclerosis Complex (previously known as Epiloia: epilepsy + anoia [mindlessness], an inappropriate and pejorative label for the disorder since up to 30% may show normal range intelligence)
- tumors of brain & skin
- Tuberous sclerosis results from an autosomal dominant trait with variable penetrance and a high mutation rate (Harris, 1998, p. 297)
- Huntington’s Chorea
- progressive neurological deterioration
- Primary Microcephaly
- likely mild MR or borderline intellectual functioning
- Neurofibromatosis
- (NFI) chromosome 17
Innate Influences
Autosomal nondysjuctions
- Down’s Syndrome (Trisomy 21, “Mongolism” was the term used by Edward Down, the British physician who gave the early, English language description of this pattern of developmental disorder)
- App. 7,000 infants in the U.S. are born with Trisomy 21 (Harris, 1998, p. 272)
- App. 1 in every 600 live births.
- moderate to mild MR, app. 10% in borderline to low normal range
- “distinctive” face (facial stigmata): epicanthan fold, upturn, outward slanting eyes, wide nasal bridge, brachycephaly, large tongue and lips, furrowed tongue; short stature; broad hands with short fingers; congenital heart defects (50%)
- Incidence correlated with maternal age.
- Some cases result from paternal nondisjunction, which appears less correlated with the father’s age.
- estimates set maternal nondisjunction in approximately 80% of cases, paternal nondisjunction in approximately 20% of cases (Jongbloet, Mulder, & Hamers, 1982)
- Three main types:
- 95% cases due to meiotic nondisjunction of autosomal chromosome pair 21 resulting in triplication of the entire 21st chromosome.
- 4% cases involves translocation of a portion of chromosome 21q to another chromosome
- 1-2% mosaic form, may be under recognized, two cell lines, one trisomic and one normal, usually less severe impairment
- Trisomy 22, 18, 13, 14, 15, 8
- Trisomy 18: Trisomy E; Edward’s Syndrome
- Trisomy 13: Patau Syndrome, Bartholin-Patau
- MR and physical defects
Sex Chromosome Nondysjunctions
- Klinefelter’s Syndrome (47, XXY)
- Turner’s Syndrome (45, XO)
- Est. to be among most common chromosomal abnormalities, showing in 3% of early fetuses; but live birth frequency of 1 in 2,500 to 5,000 female births–suspected that 99% of affected fetuses spontaneously abort
- short stature; “streak ovaries”, failure of gonadal differentiation; characteristic neuropsychological profile:
- intelligence usually in normal range
- “spatial deficit”: problems with space-form perception, spatial skill, left-right discrimination, visuomotor coordination, visual memory, lower Performance IQ than Verbal IQ scores
- XYY Syndrome: so called “super male” syndrome
Structural Abnormalities
- Ring Chromosomes (usually Ring 18): MR
- Chi du Chat’s Syndrome (short arm one #5)
- Williams Syndrome (Williams-Beuren) (#7)
- “elfin” face (“Williams syndrome face”)
- characteristic social disinhibition and friendliness toward adults, including strangers
- impaired visuospatial abilities, poor performance on facial discrimination tasks, hyperactivity, mental retardation, extreme acuteness of hearing
- hemizygous deletion on chromosome 7 in 97% of cases evaluated
- Prader-Willi Syndrome
- most involve deletions or rearrangement of chromosome 15
- 40% deletion, 30% rearrangement, 30% no discernable chromosomal abnormality, possibly point mutation
- mild to borderline MR, poor visual-spatial skills, appetite disorder, physical features
Mutations
- Tuberous Sclerosis Complex
- 25% of clinical cases may reflect spontaneous mutations
- Cardio-facio-cutaneous (CFC) syndrome
- a sporadic, complex developmental disorder: involves craniofacial features, cardiac anomalies, hair and skin abnormalities, postnatal growth deficiency, hypotonia, and developmental delay
- heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase (MAPK) pathway cause CFC syndrome. In the majority of cases there is a mutation in the BRAF gene, located on 7q (Rodriguez, et al., 2006)
- familial ideopathic epilepsy:
- an inherited epilepsy of newborns
- found to be one of the “channelopathies“, or disorders of ion channel function, associated with mutations in genes coding for a potassium channel
- unstable triplicate expansions: new mechanism of dynamic mutation due to heritable unstable DNA elements
- Fragile X syndrome
- FMR-1 (fragile X mental retardation) gene
- Prevalence of fragile X estimated to be 1 in 1,250 males and 2 in 2,500 females; found in all human gene pools. One of the more common known causes of mental retardation.
- Affected individuals show a repetitive DNA base sequence (CGG) of at least 230 repeats at the Xq27.3 site; 52 to 230 repeats produce an asymptomatic permutation carrier state; 6 to 54 repeats represent the normal range.
- Behavioral phenotype: mental retardation, ADHD, gaze aversion, speech and language delays in children with normal IQ
- possibly Huntington’s chorea
Congenital Influences
Prenatal
- General Condition of the Mother
- Malnutrition
- Specific Dietary Deficits
- Vitamin D: Rickets
- Iodine: Cretinism
- Maternal Illness
- TORCH group (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, Syphilis)
- the “Rubulla bulge” refers to children born with Rubulla related birht defects resulting from 1964 epidemic of “German measles”; an estimated 20,000 to 30,000 children were affected with approximately 8,000 born deaf, 3,500 born blind, 1,790 cognitively impaired. (Thompson & O’Quinn, 1979)
- Rubulla as been virtually eliminated in the U.S.
- HIV
- TORCH group (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, Syphilis)
- Blood Type Incompatibility
- Rh- mothers; Rh+ children
- ROGAM
- Drugs: quantitative vs. qualitative effects
- Thalidomide
- Progestines: Progestine-induced hermaphroditism
- Alcohol: Fetal Alcohol Syndrome
- Nicotine
- Chemical Toxins: PCB’s and IQ
- Radiation
Natal
- Anoxia
- Fetal Distress
- Cerebral Palsy
- Prematurity (& Postmaturity)
- Gestation age vs. gestation weight
- Birth Weight (premature)–% Disability (IQ<70, CP)
- <1,500 grams —————-4%
- <1,000 grams —————-10%
- < 750 grams —————–18%
Constitutional
- Illness
- Toxic Exposure
- Brain Injury
Learning (experiential) influences on development
Mechanisms of Learning
- respondent (classical or Pavlovian conditioning):
- associative learning based on contiguous pairing
- esp. relevant for maintenance of homeostasis and possible
- development of emotional behavior
- operant (instrumental)
- learning from consequences (rewards, punishments)/contingencies
- esp. relevant for influencing the level of performance/frequency of actions
- observational (vicarious learning, modeling)
- learning from noting the actions and experiences of others, may be
- symbolic (based on stories, reading, etc.)
- esp. relevant for language acquisition and social development
Social Interaction
- Among the major effects of social engagement are:
- 1) attachment phenomenon
- 2) language development
- 3) cognitive development (Vygotsky)
- 4) social skill acquisition
- 5) self-image, gender identity, values & attitudes
- The agents of social development include:
- 1) parents
- 2) siblings & extended family
- 3) peers
- 4) subgroups (clubs, church/synagogue/mosque, gangs)
- Interaction of Biology and Experience
- Temperamental traits (possibly more biological) interact with child rearing patterns (possibly more experiential) to produce unique outcomes, for good and ill.
- Children influence, as well as are influenced, by their environments.
- Risk and protective factors are often interactive: their joint effects are seldom simply additive or linear.
- 2 risk factors are usually worse than 1, but often are more then “twice” as bad as 1.
- Particular combinations of risk factors are often especially destructive (or more benign):
- “difficult temperament” + inconsistent parenting is an especially unfortunate combination.
Maternal Age
Mother’s Age | Trisomy 21 Incidence per 1,000 Live Births |
15-19 | 0.6 |
20-24 | 0.5 |
25-29 | 0.8 |
30-34 | 0.8 |
35-39 | 2.8 |
40-44 | 7.6 |
45-49 | 27.5 |
Channelopathies
(4-17-07)
Voltage-gated sodium and potassium channels are proteins; they span the width of the cell membrane and cantain a fluid-filled pathway, the ion pore, through which ions pass. Ion channels are present in every cell of the body, not only neurons. In 2003, 51 years after ionic hypothesis formulated by Hodgkin and Huxley (Nobel prize for physio/med in 1963), Roderick MacKinnon received Nobel prize in chemistry for first 3D picture of atoms that form the protein of two ion channels, a non-gated potassium channel and a voltage-gated potassium channel.
Mutations in the genes that code for ion channel proteins lead to diseases referred to as “channelopathies, or disorders of ion channel function. “Familial ideopathic epilepsy”, an inherited epilepsy of newborns, has been found to be associated with mutations in genes coding for a potassium channel.