Genetics Flashcards
1
Q
Dysmorphology (3)
A
- Aspect of clinical genetics that involves the syndrome diagnosis in children who have unusual facial features, congenital malformations and often have associated cognitive and motor delays.
- > 3500 syndromes
- Some are instinctive recognized by past experience, others involve pieces of puzzles
2
Q
Cleidocraniodysostosis
A
rare; abnormal pelvis, unable to delivery babies as a female
3
Q
Blaschko’s Lines
A
fine lines that occur from back to the front that may cause a pigment difference; clinical expression of generalized altered stout
- May see neurocutaneous disorders following the lines of Blaschko’s
- Lines of normal cell development in the skin
4
Q
Chromosomal Disorders (3)
A
- Part or whole chromosome is missing or duplicated
- Example: Down syndrome
- Tested by Karyotype
5
Q
Microdeletion or microduplication syndromes (4)
A
- A very small piece of chromosome is missing or duplicated
- Cannot be seen on karyotype
- Examples: DiGeorge, velocardiofacial; williams syndrome
- Tested by Fish/ Array comparative hybridization (ACGH)
6
Q
Single Gene Disorders (6)
A
- A mutation in a single gene causing a disorder
- Dominant (AD), recessive (AR), X-linked
- AD: Marfan syndrome, neurofibromatosis, type 1
- AR: cystic fibrosis, sickle cell disease, Tay Sachs disease
- X-linked: Duchenne Muscular dystrophy
- Testing: Mutation analysis, DNA sequencing and or deletion testin
* Usually micro-array
7
Q
Triplet Repeat Disorders (4)
A
- Trinucleotide repeats in certain genes exceeding the normal, stable threshold which differences for each gene.
- Results may be interference of the normal gene or gene product
- Example: Fragile X, Huntington disease
- DNA tests for number for repeats
* Male child that will have significant developmental delay
8
Q
Variable Penetrance
A
When two patients with the same disorder that don’t have the same clinical manifestation (ex: Turner Syndrome, Marfan’s Syndrome); how the gene is expressed in a patient
Ex: Some children with Down Syndrome can be very high functioning and some aren’t even able to talk (low functioning)
9
Q
Multifactorial Disorders (3)
A
- A combination of genetics and environment
- Examples: Cleft lip and palate; clubfeet; pyloric stenosis
- No current testing available
10
Q
Epigenetic Disorders (3)
A
- Changes are not in the sequencing but in the expression of the DNA
* Changes in expression but not sequencing - Examples: Prader Willi; Beckwith-Weidman syndrome
- Testing by Methylation analysis
11
Q
Diagnosing Genetic Diseases (4)
A
- Informs reproductive decision
- Preventative strategies
- Explanation of what you can do
- Massive parallel sequencing will explain what is causing the patient’s problem
* Take an 11 year old who has a sudden cardiac arrest; Genome would tell the patient’s need for implant
12
Q
Sequences
A
A defect occurs and subsequent development is abnormal
13
Q
VACTERLS ASSOCIATION
A
V -- vertebral anomalies / dysgenesis, vascular anomalies A -- anal atresia C -- Cardiac anomalies T -- trachea-esophageal (T-E) fistula E -- esophageal atresia R -- renal anomalies, radial dysplasia L -- Limb anomalies S - Single umbilical artery
14
Q
CHARGE ASSOCIATION
A
C" for coloboma "H" for heart defects "A" for atresia choanal "R" for retardation of growth and development "G" for genitourinary problems "E" for ear abnormalities
15
Q
Complexes
A
Abnormalities in adjacent structures; something occurs on one side of the face and may cause the rest of the face to cause an anomaly
16
Q
Goldenhar syndrome (6)
A
- Affects one side of the face only. :
- Partially formed or totally absent ear (microtia)
- Chin may be closer to the affected ear
- One corner of the mouth may be higher than the other
- Benign growths of the eye
- Missing eye
17
Q
Major Anomalies (2)
A
- Easily identified
2. Involve easily identified malformations
18
Q
Congenital Anomalies (2)
A
- Present at birth
2. Does not imply cause
19
Q
Minor Anomalies (3)
A
- Physical difference that occur in fewer than 4% of the population
*if they occur in more than 4% then it is normal phenotypic variation
Ex: specific creases are found on Asian children as a normal phenotypic indication … epicanthial folds found in Asian children greater than 4% of the time - More commonly in areas that are more variable and complex: face, hand
- 70% in these two area
20
Q
Types of Minor Anomalies (5)
A
- Some minor anomalies are markers for occult major malformations
- Sacral tuft of hair or deep sacral dimple: associated with occult spinal dysraphism
- Many genetic syndromes are specific patterns of minor anomalies occurring together
- Specific minor abnormalities of face, hands, feet: Down syndrome
- Three or more minor anomalies increased risk of having major malformation –> Assess for major malformation
21
Q
Most common external anomalies are in the… (4)
A
- Face
- Auricle
- Hands
- Feet
22
Q
Recognition of Minor Anomalies (3)
A
- Some minor anomalies run in families as a single variation; As high as 14% of newborns have at least one minor anomaly.
- If there are three or more minor anomalies, there is approximately a 20% chance of a major anomaly.
- Represent deformation due to altered mechanical forces affecting the development of otherwise healthy tissue
* Very common to have minor anomaly; some are just developmental deformations that are not an issue
23
Q
Normal Phenotypic Variants (10)
A
- Saddle (mildly upturned nose)
- Mild to moderate in bowing of lower leg
- Sacral dimple, not deep
- Mild syndactyly of second and third toes
- Toenail hypoplasia in the newborn
- Hydrocele of the testicle
- Epicanthal folds
- Unilateral epicanthal fold is indicative of torticollis
- Slanting of the palpebral fissures
- Brushfield spots (20% of normal newborns)
24
Q
Frequent Newborn Findings (2)
A
- Normal Phenotypic variant
- STORK BITES: Fine non-elevated pink to red capillary hemangioma at nape of neck, over central forehead and eyelids and in the lumbosacral region
25
Skull Physical Assessment Findings that may be significant (5)
1. Asymmetrical head or face
2. Brachycephaly (high hat)
3. Flattened occiput
4. Fontanels too large or small
5. Overlapping sutures (risk with Craniocyostosis)
26
Brachycephaly
most likely do to closure of coronal or lamboidal (or both) sutures
27
head shapes (3)
1. Triangular shape – metopic suture or frontal suture closed prematurely
2. When saggital suture closes prematurely -- long narrow
3. When coronal or lamboidal sutures closes prematurely -- Brachycephaly
28
Facial Proportions (3)
1. Micrognathism: small mandible
2. Retrognathism: Receding
3. Prognathism (Projection of jaw beyond that of forehead)
29
Minor Anomalies of the Face (13)
1. Ocular hypertelorism ( A low nasal bridge will give the appearance of hypertelorism
2. Telecanthus is consequence of lateral displacement of the inner canthi
3. Synophrys
4. Fused eyebrows
5. Flat bridge of nose
6. Hypotelorism
7. Anteverted nostrils
8. Epicanthal fold
9. Iris freckles
10. Upward palpebral slant (mongoloid slant)
11. Downward palpebral slant (antimongoloid slant)
12. Blue sclera
13. Different eye colors
30
Minor Malformations (2)
1. Circular pattern of hair (cowlick)
| 2. Kinky hair, brittle hair including eye brows
31
Minor Anomalies with Hair Patterning (4)
1. Look for unusual hair pattern
2. Low set hair line
3. Widow's peak
4. Webbed neck
32
Assymetrical Crying Faces (5)
- - Higher incidence of congenital heart disease
1. Ventriculoseptal defects
2. Atrial septal defect
3. Patent ductus arteriosus
4. Tetralogy of Fallot
5. Velocardiofacial syndrome (22q11 deletion syndrome)
33
Telorism
Spacing between the eyes
Hypotelorism --> less space between the eyes
Hypertelorism --> increased space between the eyes
34
Eye Distances (3)
1. Palpebral fissure length; Measure palpebral fissures; it is the space from the inner canthus to the outter canthus (how big eye opening is)
2. Mean length in a five year old is 2.5 cm
3. Short palpebral fissures is minor anomaly
35
Slanting of Palpebral Fissures (4)
1. Normal Horizontal or upward slanting with an angle 10 degrees
3. Downward slanting
4. External canthus lower than the internal canthus
36
Heterocromia
different colors in each eye; needs to be referred to the eye doctor; associated with higher risk of retinoglastoma (need dilated eye exam)
*Can also be associated with some genetic syndromes
37
Wilson Disease (Hepatolenticular Degeneration) (4)
1. Age of onset for Wilson disease - between 8 years to the mid-50's
Presents as..
1. Severe liver cirrhosis.
2. Kayser-Fleischer rings: deposition of copper in the cornea (around the eye)
3. Accompanied by neurological disorder.
4.Kayser-Fleischer rings; occur around the eye; think about Wilson’s Disease
38
Minor Anomalies of the Auricular Region (8)
1. Large ears
2. Lop ear
3. Lack of lobulus
4. Lobe crease
5. Thick helix or attached to scalp
6. Protruding ears (due to lack of development of the posterior auricular ear muscle
7. Low set ears
8. Ears slanted greater than 15 degrees from the perpendicular
39
Preauricular tags (3)
1. Found anywhere along a line drawn from the tragus to angle of mouth
2. Bilaterally in 6% of affected individuals
3. Autosomal dominant inheritance pattern
40
Preauricular pits
Small openings at anterior margin of the helix
41
Goldenhar Syndrome (7)
1. Look for facial asymmetry and microtia (small ear)
2. Unilateral or bilateral Hemifacial Microsomia (HFM)
3. Aural Atresia - Absence of the auditory canal
Other Problems:
4. cleft lip/palate
5. hearing loss
6. epibulbar dermoids (benign tumors)
7. vertebral anomalies and organ abnormalities including kidney and heart anomalies
42
PA Findings of Mouth that maybe significant (7)
1. Small or large tongue (micro or macroglossia)
2. Misshapen, missing or extra teeth
3. Early loss of teeth
4. Late eruption of teeth
5. Thin upper lip
6. Cleft uvula
7. Smooth or abnormal philtrum
43
Enamel Hypoplasia
defect in tooth enamel that results in less quantity of enamel than normal
44
Anodontia
Congenitally missing teeth
45
Hypodontia
Congenital absence of one or a few permanent teeth w/o any systemic disorders
46
Hair PA Findings that may be significant (4)
1. Excess body hair
2. Hairline and hair distribution
3. Large section of white hair in front (Waardenburg)
4. Sparse or brittle hair
47
Waardenburg Syndrome: Major Criteria (5)
* Need two major or one major plus two minor to categorize as Waardenburg
1. Sensorineural hearing loss
2. Iris pigmentary abnormality (two eyes different color or iris bicolor or characteristic brilliant blue iris)
3. Hair hypopigmentation (white forelock or white hairs at other sites on the body),
4. Dystopia canthorum (lateral displacement of inner canthi
5. First-degree relative previously diagnosed with Waardenburg syndrome.
48
Waardenburg Syndrome: Minor Criteria (5)
* Need two major or one major plus two minor to categorize as Waardenburg
1. Skin hypopigmentation (congenital leukoderma/white skin patches(Face, trunk, or limbs - 30-36 %)
2. Medial eyebrow flare (synophrys)
3. Broad nasal root
4. Hypoplasia alae nasi
5. Premature graying of the hair (before age 30) .
49
Growth Dysmorphologies (5)
A) Ht/Percentile for age:
1. Short stature
2. Tall stature
B) Weight/ percentile for age
3. Under or overweight for height
C) Head circumference
4. Macrocephaly
5. Microcephaly
50
Hair Dysmorphologies (8)
1. Normal
2. Unusual texture
3. Sparse/alopecia
4. Low posterior hairline
5. Low anterior hairline
6. Unusual pattern extra whorls
7. Unruly, uncombable
8. White forelock
51
Face Dysmorphologies (5)
1. Normal
2. Asymmetry
3. Round
4. Long/narrow
5. Myopathic - consisting of bilateral ptosis and inability to elevate the corners of the mouth, due to muscle weakness; occurs with Myasthenia Gravis
52
Myotonia
Continuous contraction of the muscles
53
Myotonic dystrophy
can’t contract the muscles; can’t release smile/can’t contract muscles
*Characterized by continuous contractions (myotonia); on physical exams they will be unable to relax facial expressions, won’t be able to release hands once it is closed, wasting of sternocleidomastoid muscle, may have cataracts, drooping of face and eyes
54
Eye Dysmorphologies (12)
Eyebrows
1. Arches
2. Medial flare
Eyelids
3. Ptosis
Eye fissures
4. Narrow
5. Wide
Eye slant
6. Antimongoloid
7. Mongoloid
8. Blue Sclera
9. Brushfield spots of iris
Pupils
10. Telecanthus -increased distance between the medial canthi of the eyes, while the inter-pupillary distance is normal
11. Hypertelorism
12. Hypotelorism
55
Ear Dysmorphologies (6)
1. Normal
2. Simplified
3. Low set
4. Posteriorly rotated
5. Pits/grooves
6. Tags
56
Palate Dysmorphologies
1. High arched Palate
2. Broad Alveolar ridges
3. Bifid uvula
57
Neck Dysmorphologies (7)
1. Normal
2. Prognathism
3. Micrognathia
4. Redundant skin
5. Torticollis
6. Pits/sinuses
7. Masses
58
Syndactyly
Fusion of soft tissue between fingers
59
Extra Digist
1. Postaxial: on pinky finger side
Type A- normal size, Type B- very small
2. Preaxial on thumb side
60
Clinodactylyl
Curved fingers (can tell finger is curving down); Minor anomaly
61
Hypoplastic Hands
Underdeveloped; Minor anomaly
62
Camptodactylyl
Broader fingers; Minor anomaly
63
Minor Anomalies of Hands (6)
1. Clinodactyly - curved
2. Syndactyly – joined
3. Hypoplastic -
4. Asymmetric length
5. Camptodactyly – borader
6. Malportion or disharmony in the length of particular segment of the hand
64
Palmer Creases (6)
1. Formed from second to fifth month
2. Once the palmar creases are formed, unchanged throughout life
3. Single palmar crease occurs unilaterally in 4 % of general population
4. Single palmar crease occurs bilaterally in 1% of the general population
5. In Chinese population: normal phenotypic variant 16.8% of Chinese have unilateral crease
6. Carefully evaluate for other problems
65
Sydney Line
crease on palm; : Head line goes completely across palm
66
Normal Palmar Crease
On Heart, head, life lines
67
Single Palmar Crease
Heart and head joined
68
Positive Thumb Sign
Long narrow, tapering fingers = eractodactyly; can take finger and close it and the thumb goes out the other end because its so long
*Indicates connective tissue disorder
69
Positive Wrist Sign
Take hands, wrap it around wrist, if hands are long they overlap
70
Minor Anomalies of the Feet (6)
1. Asymmetric length of toes
2. Clinodactyly of second toes with overlapping
3. Syndactyl
4. Short broad toenail
5. Deep crease between hallux and second toe
6. Wide gap between hallux and second toe
71
arachnodactyly
fingers are long, slender, and curved. They look like a spider's legs.
72
Significant PA Findings of Extremities (7)
1. Abnormally positioned feet
2. Arachnodactyly
3. Extremely long and thin extremities
4. Loose joints
5. Single Palmar crease
6. Polydactyly - unusual # of extremities
7. Short or tall stature
73
Pectus Excavatum (2)
1. Posterior angulation of the sternum toward the spine and abnormalities of the costal cartilages; If you push the chest in, it displaces more towards the right
2. Occurs with arachnodactyly and dilation of aorta
74
Minor Anomalies of Genitalia (2)
1. Hypoplasia of the labia majora
| 2. Shawl scrotum
