How do Mutations Affect Health and Craniofacial Development

Question 1

Mutations are an important

cause of

Answer 1

poor health

Question 2

The average child is born with an estimated
— to — new mutations that were not present
in the parents

Answer 2

100-200

Question 3

– in – infants is born with a diagnosable
genetic condition that can be attributed to a
single major mutation

Answer 3

1 in 50

Question 4

types of genetic diseases (3)

Answer 4

chromosome disorders
single gene disorders
multifactorial or complex

Question 5

Chromosome Disorders (5)

Answer 5

Aneuploidy, Rearrangements/Translocations, Deletions,

Insertions, Duplications

Question 6

Single Gene Disorders (3)

Answer 6

Dominant, Recessive, Codominant

Question 7

Multifactorial or Complex (2)

Answer 7

Multiple genes, gene-environment

Question 8

aneuploidy

Answer 8

An aberration in chromosome number caused
by faulty segregation of chromosomes during
mitosis or meiosis

Question 9

1 in 400 infants is born with —

Answer 9

aneuploidy

Question 10

Most cases of aneuploidy originate in female

meiosis I and the risk rises with — —

Answer 10

maternal age

Question 11

example of aneuploidy with oral manifestations

Answer 11

Down syndrome

Question 12

Down syndrome
1866
1959
2000

Answer 12

• 1866 - John Langdon Down, an English
physician, published an accurate description of
a person with Down syndrome
• 1959 - Jérôme Lejeune identified Down
syndrome as a chromosomal condition
• 2000 - an international team of scientists
successfully identified and catalogued each of
the approximately 329 genes on chromosome
21

Question 13

Down syndrome (trisomy 21)

Answer 13

full or partial extra copy of chromosome 21

Question 14

how many babies in the US are born with downs syndrome

Answer 14

1 in 700 babies in the US

Question 15

about — per year

Answer 15

6000

Question 16

most common chromosomal condition

Answer 16

Down syndrome (trisomy 21)

Question 17

Nondisjunction occurs in –% of down syndrome cases

Answer 17

> 95%

Question 18

Mosaicism occurs in ~–% of Down syndrome cases, least common form

Answer 18

1%

Question 19

Translocation occurs in ~–% of cases

Answer 19

4%

Question 20

translocation is

Answer 20

full or partial copy of chromosome 21 attaches to

another chromosome, usually chromosome 14

Question 21

only factor that has been linked to an increased
chance of having a baby with Down syndrome resulting from
nondisjunction or mosaicism

Answer 21

Maternal age

Question 22

However, due to higher birth rates in younger women, 80% of children with Down syndrome are born to women under – years of age

Answer 22

35

Question 23

5% of the cases have been traced to the —

Answer 23

father

Question 24

— is not a factor in trisomy 21 (nondisjunction) and mosaicism

Answer 24

Heredity

Question 25

However, in one-third of cases of Down syndrome resulting from translocation there is a hereditary component – accounting for about

Answer 25

1% of all cases of Down syndrome

Question 26

Down syndrome symptoms

Answer 26

• Low muscle tone, • Small stature, • Cognitive delay (very mild to severe), and • Transverse palmar crease • a single deep crease across the center of the palm • each person with Down syndrome is a unique individual and may possess these characteristics to different degrees, or not at all • 80% of adults with Down syndrome reach age 60, and many live even longer

Question 27

About half the children with Down syndrome are born with some type of congenital --- ---. These heart problems can be life-threatening and may require surgery in early infancy.

Answer 27

heart defect

Question 28

--- ---: Some people with Down syndrome may have a misalignment of the top two vertebrae in the neck (atlantoaxial instability). This condition puts them at risk of serious injury to the spinal cord from overextension of the neck

Answer 28

spinal problems

Question 29

--- ---: GI abnormalities occur in some children with Down syndrome and may include abnormalities of the intestines, esophagus, trachea and anus. The risk of developing digestive problems, such as GI blockage, heartburn (gastroesophageal reflux) or celiac disease, may be increased.

Answer 29

Gastrointestinal (GI) defects

Question 30

--- ---. Because of abnormalities in their immune systems, people with Down syndrome are at increased risk of developing autoimmune disorders, some forms of cancer, and infectious diseases, such as pneumonia.

Answer 30

immune disorders

Question 31

--- ---. Because of soft tissue and skeletal changes that lead to the obstruction of their airways, children and adults with Down syndrome are at greater risk of obstructive sleep apnea.

Answer 31

Sleep apnea

Question 32

---. People with Down syndrome have a greater tendency to be obese compared with the general population.

Answer 32

Obesity

Question 33

---. Young children with Down syndrome have an increased risk

Answer 33

Leukemia

Question 34

People with Down syndrome have a greatly increased risk of ---. signs and symptoms may begin around age 50. Having Down syndrome also increases the risk of developing Alzheimer's disease.

Answer 34

dementia

Question 35

Down syndrome may also be associated with other health conditions, including (6)

Answer 35

endocrine problems, dental problems, seizures, ear infections, and hearing and vision problems

Question 36

People with Down syndrome should always be referred to as --- first

Answer 36

v

Question 37

Instead of “a Down syndrome child,” it should be “---.” Also avoid “Down’s child” and describing the condition as “Down’s,” as in, “He has Down’s.”

Answer 37

a child with Down syndrome

Question 38

Down syndrome is a (2), not a disease.

Answer 38

condition or a syndrome

Question 39

People “---” Down syndrome, they do not “suffer from” it and are not “afflicted by” it.

Answer 39

have

Question 40

Typically developing” or “---” is preferred over “normal.”

Answer 40

typical

Question 41

what has replaced “mental retardation” as the | appropriate term

Answer 41

“Intellectual disability” or “cognitive disability”

Question 42

--- strongly condemns the use of the word “retarded” in any derogatory context. Using this word is hurtful and suggests that people with disabilities are not competent.

Answer 42

NDSS

Question 43

Down vs. Down’s

Answer 43

down not downs

Question 44

what causes chromosomal rearrangements

Answer 44

by chromosome breakage or by recombination between mispaired chromosomes during meiosis

Question 45

Only chromosomal rearrangements that change the --- or that break up an important gene are likely to cause disease

Answer 45

copy number of genes

Question 46

1 in 1000 infants is born with a --- chromosomal rearrangement

Answer 46

symptomatic

Question 47

examples with oral manifestations

Answer 47

cri-du-chat syndrome

Question 48

Cri du chat syndrome is known as

Answer 48

Cat’s cry

Question 49

cat's cry

Answer 49

infants with this condition often have a high-pitched cry that sounds like that of a cat

Question 50

Cri du chat syndrome affects

Answer 50

1 in 20-50,000 newborns

Question 51

symptoms of Cri du chat syndrome (6)

Answer 51

``` • Intellectual disability and delayed development • Small head size (microcephaly) • Low birth weight • Weak muscle tone (hypotonia) • Transverse palmar crease • Some have heart defects ```

Question 52

Cri du chat syndrome facial features

Answer 52

``` • Widely set eyes (hypertelorism) • Low-set ears • Small jaw (micrognathia) • Rounded face (moon facies) • epicanthal folds, • broad nasal bridge, • downward-slanting palpebral fissures ```

Question 53

single gene disorders aka

Answer 53

mendelian disorders

Question 54

single gene disorders are mutations in a

Answer 54

single gene

Question 55

expressed in heterozygotes, who carry | a single copy of the mutation

Answer 55

dominant

Question 56

Severe dominant diseases are often caused by a

Answer 56

new | mutation

Question 57

expressed only in homozygotes, who | have the mutation in both copies of the gene

Answer 57

recessive

Question 58

multifactorial diseases aka

Answer 58

polygenic diseases or complex diseases

Question 59

multifactorial diseases are caused not by a single major mutation but by (2)

Answer 59

interacting genetic and environmental risk | factors

Question 60

Most of the common diseases, from (3), are | multifactorial

Answer 60

allergies to | diabetes and coronary heart disease

Question 61

Median palatal process (derived from medial nasal processes and frontonasal process) - forms the --- ---

Answer 61

primary | palate

Question 62

--- --- - derived from the frontonasal prominence

Answer 62

Nasal Septum

Question 63

--- --- - derived from the maxillary process of the first pharyngeal arch

Answer 63

Palatal shelves

Question 64

Secondary palate separates the

Answer 64

nasal cavity from the oral cavity

Question 65

what is the secondary palate needed for? (5)

Answer 65

``` swallowing (feeding) taste vomitting breathing speech ```

Question 66

- -- of CPO is different than that of Cleft Lip with Cleft Palate (CL/CP) - CPO is a specific defect in palatogenesis (weeks 7-10) - CP in CL/CP is a secondary defect for a failed lip fusion (weeks 4-7)

Answer 66

Etiology

Question 67

Syndromic cleft palate ~ ---% of cases (Cleft palate a phenotype of a known syndrome)

Answer 67

30

Question 68

Non-syndromic cleft palate – ---% of cases (not associated with a known syndrome)

Answer 68

70

Question 69

identified causes of cleft palate (3)

Answer 69

environmental nutritional/metabolic genetic

Question 70

Environmental

Answer 70

alcohol, phenytoin, retinoic acid, radiation (X-rays), | TCDD...

Question 71

Nutritional / metabolic

Answer 71

low methionine, low folic acid, maternal DM, | hypervit. A

Question 72

Genetic

Answer 72

350+ Mendelian disorders, chromosomal | aberrations

Question 73

--- is not fully understood

Answer 73

Pathogenesis

Question 74

cleft lip and palate is not just an interesting biological problem, or just an aesthetic handicap, but also (7)

Answer 74

``` ● family: shock, guilt, anxiety, depression ● babies: failure of suckling, later eating problems ● dental defects, malocclusion ● speech difficulties ● infectious complications, hearing impairment ● multiple surgery and hospital care ● psychological traumatization ```

Question 75

Current prenatal screening does a poor job of detecting --- ---

Answer 75

facial anomalies

Question 76

Cleft palate is a very early --- event, screening occurs 18-22 weeks

Answer 76

intrauterine

Question 77

(2) do not exist to easily detect a cleft palate

Answer 77

Technology and resources

Question 78

Etiology of cleft palate is multifactorial (and still poorly known): (5)

Answer 78

``` •Gene - Environment interactions •Genetic susceptibility •Environmental toxins •Nutrition •Life style (smoking, alcohol etc) ```

Question 79

A problem caused by the therapy-

Answer 79

defective maxillary growth

Question 80

A substantial amount of knowledge about the (2) of cleft palate has been accumulated

Answer 80

developmental biology of palate and the | etiopathogenesis

Question 81

Challenges:

Answer 81

• Lifestyle and environmental risk factors • Gene - environment interactions (still largely an unknown variable) • A number of molecules expressed in the palate during fusion is humbling • We know many of them - however, we know very little about their regulation and how different signaling pathway intersect and converge