Genetics - General and Down Syndrome

Question 1

Achondroplasia Features (4)

Answer 1

1. Macrocephaly
2. Short limbed dwarfism
3. Tremendous orthopedic problems - Always followed by orthopedics
4. Hearing problems

*Need to be followed closely

Question 2

Myotonic Dystrophy (8)

Answer 2

1. Autosomal dominant
2. Frontal balding
3. Cataracts
4. Progressive myotonia
5. Infertility
6. Cardiac conduction defects
7. MYOTONIA → inability to let go; continuous contraction of a muscle
8. Gets worse with each generation

Question 3

Neurofibromatosis Type 1 (5)

Answer 3

1. Café au lait spots
2. Neurofibromas
3. Lisch nodules
4. Optic glioma – Biggest risk
5. Macrocephaly

Question 4

Fragile X overview of manifestations (4)

Answer 4

a. Mental retardation
b. Long appearing face
c. Large ears
d. Macro-orchidism later in childhood

Question 5

Charcot Marie Tooth Type 1

Answer 5

Progressive sensory and motor neuropathy

Question 6

Familial adenomatous polyposis (5)

Answer 6

1. Adenomatous polyps of colon
2. High risk for colorectal cancer in early adulthood
3. Families do not get diagnosed, kid will get dx then mother
4. Polyposis = high risk of cancer in early adulthood
   * Kids need to be followed by GI
5. Genetic testing not done until child can give consent

Question 7

Ethical Issues with Genetic Testing in Pediatrics (4)

Answer 7

1. Identification of the genetic condition must provide a clear benefit to the child
2. Systems need to be in place to confirm the diagnosis
3. Treatment and follow up must be available for affected newborns
4. In order to go a test for genetic problem = need clear benefit by early identification
   * Huntington = occurs in late adulthood; do not need to test for

Question 8

AAP Recommendations with Genetic Testing (6)

Answer 8

1. Newborn screening test should be reviewed and evaluated periodically
2. Genetic tests require a process of informed parental consent and the older child’s assent
3. AAP does not support the broad use of carrier testing or screening in children.
4. Genetic testing for adult-onset disease should be delayed until adulthood.
   a. Insurance companies may discriminate against a patient if they find out about a disorder even though there are laws against this
5. Genetic screening and testing may not be well understood
   a. May cause psychological harm, stigmatization and discrimination.
6. Delay adult onset disease until adulthood

Question 9

Concerns about genetic testing (5)

Answer 9

1. Knowledge of increased risk status may trigger psychological affects
2. May cause discrimination by employers.
3. Testing for BRCA 1 / BRCA 2 tests as well as HNPCC (hereditary nonpolyposis colon cancer)
4. Initially was discouraged in adult.
5. Testing in childhood inappropriately eliminates possibility of future choice due to risks of stigma and discrimination

Question 10

Down Syndrome Genetic Alterations (4)

Answer 10

1. 3 different types
2. In 95%, Down syndrome is result of a random nondisjunction (trisomy 21)
3. Less commonly, it occurs as mosaicism where some cells are affects and others are normal
   i. Mosaic vs. Normal cells is important to understand
4. Balanced translocation, often involves chromosome 21 and 14

Question 11

DS Risk Factors (5)

Answer 11

1. Affects males and females equally
2. Advanced maternal age
3. Previous child with Down syndrome or another chromosomal abnormality
4. Parental balanced translocation
5. Parents with chromosomal problems (known chromosomal problems)
   * Rate goes up with age of mother, affects males and females equally

Question 12

Children with Down Syndrome, Phenotypic Signs: Head (6)

Answer 12

1. Midface hypoplasia
2. Small brachycephalic head with epicanthal folds
3. Flat nasal bridge,
4. Upward slanting palpebral fissures
5. Brushfield spots
6. Small mouth

Question 13

Children with Down Syndrome, Phenotypic Signs: Ears (3)

Answer 13

a. Small ears
b. Neck
c. Excessive skin at the nape of the neck

Question 14

Children with Down Syndrome, Phenotypic Signs: Hands and Feet (4)

Answer 14

1. Single palmar crease and short fifth finger with clinodactyly
   * Clinodactyly; short 5th finger with curve, short ears, narrow canals
2. Wide space, often with a deep fissure between the first and second toes
   * Normal phenotypic variant
3. Lymphedema – Lymphedema at birth (seen with turner too)
4. Brachydactyly (shortened digits)

Question 15

Children with Down Syndrome, Phenotypic Signs: Skin

Answer 15

Dry

Question 16

Down Syndrome Complications: Neurological

Answer 16

Developmental disability is variable, ranging from mild (IQ: 50–70), to moderate (IQ: 35–50), and only occasionally severe (IQ: 20–35)

Question 17

Down Syndrome Complications: Cardiac

Answer 17

Increased risk of congenital heart defects (50%)

*Must refer all DS children to cardiology even if you don’t hear a murmur

Question 18

Down Syndrome Complications: GI (2)

Answer 18

1. Hirschsprung’s disease (1%)
2. Gastrointestinal atresias (12%
   * Need to look carefully for atresia and down syndrome in nursery

Question 19

Down Syndrome Complications: Musculoskeletal (5)

Answer 19

1. Hypotonia
2. Extreme flexibility
3. Wide gap between first and second toe
4. Acquired hip dislocation (6%) – Due to hypotonia
5. Ankle pronation and pes planus

Question 20

Down Syndrome Complications: Other (13)

Answer 20

1. Otitis media (50%–70%)
2. Obstructive sleep apnea (50%–75%)
3. Signs of congenital heart disease—50%
   * Can develop cardiac disease with sleep apnea that goes untreated
4. Endocardial cushion defect most common (45%) with ventricular septal defects (35%) second
5. Signs of hypothyroidism and other endocrine problems—15%;
   * Yearly thyroid screen, NBS, 6 months, every year after
6. By adulthood, >60% will develop hypothyroidism
7. Signs of anomaly of GI tract 5%;
8. Celiac disease 15%
9. Ligamentous laxity—100%
10. Hematological—leukemia (0.1%) – Do CBC every year due to risk of leukemia
11. Eye—eye disease (60%), including cataracts (15%), and severe refractive errors (50%)
    * Should get referral to optho and hearing
    * Cataracts and myopia
12. Obesity—50% by early childhood
13. Premature aging

Question 21

Management of the Child with Down Syndrome (4)

Answer 21

1. Pre or postnatal karyotype
2. Radiographic swallowing assessment if marked hypotonia, slow feeding, choking with feeds
3. Recurrent or persistent respiratory symptoms and signs, FTT
4. CBC with differential yearly to identify those with leukemia
   a. 10 to 15 fold increased risk
   b. Early CBC and do it every year
   c. Do not radiate spine unless they have motor dysfunction, gait disturbance
   d. T-cell dysfunction; cold they get pneumonia

Question 22

Management of the Child with Down Syndrome: Symptoms of atlanto-axial instability (2)

Answer 22

1. Neck pain, decreased range of motion of the neck, gait disturbance, bowel or bladder dysfunction, hyperreflexia or paresthesia
2. Routine radiographs for atlanto-axial instability are no longer recommended

Question 23

Management of the Child with Down Syndrome: Optho evaluation (3)

Answer 23

1. Evaluate for cataracts in the first year of life
2. Every two years between 3 to 5 years then yearly after this (50% risk of refractive errors between 3 to 5 years)
   * Every 2 years between 3-5 then yearly for refractive
3. Prompt referral for associated conditions-Regular Ophthalmology evaluation/ENT

Question 24

Management of the Child with Down Syndrome: Other (12)

Answer 24

1. Primary prevention via education re: risk factors; secondary prevention via prenatal diagnosis
2. Monitor for growth and family support every well visit
3. Annual screening TSH, hemoglobin, hearing screen if normal screening at 6 months
4. Initial evaluation by cardiology to rule out congenital heart defect even if no murmurs are heard
5. Screen for celiac disease if symptomatic; screen for symptoms at every visit
   * If they have anemia you need to consider celiac
6. If constipation, evaluate for limited diet or fluids, hypotonia, hypothyroidism, GI malformation, Hirschsprung
   * Can prescribe miralax safely
7. Early intervention by PT, OT, speech therapists; special education; review individualized educational plan
   * Early intervention: 3x per week OT, PT, speech
8. Genetic counseling for parents and older siblings
9. Periodic full history and physical with sensory and developmental evaluations
10. Nutritional support
11. Observe for signs of autism and refer if suspicious of ASD
    * Co-morbid ASD with down syndrome
    * IF kid has solely down syndrome they do not get as many services compared with ASD
12. If chronic cardiac or pulmonary disease, 23-valent pneumococcal vaccine at age >2 y
    a. Get prevnar at age 2

Question 25

Children with Down Syndrome: Parental Education (9)

Answer 25

1. Increased risk of infections
2. Encouragement of self help skills
3. Care of dry skin
   a. Dry skin is a huge issue; can prescribe for lotion
   b. DS with extremely dry skin - will cover
   c. Delayed dentition = thyroid go hand in hand
   d. Onset of weakness, change in reflexers, remember atlano-axio-instability
4. Avoidance of contact sports and trampolines
5. Call provider if changes in gait, use of hands, bowel or bladder dysfunction or new onset of weakness due to risk of atlanto-axial instability
6. Discuss cervical spine protection during anesthesia
7. Awareness of delayed dentition
8. Psychosocial changes during puberty
9. Social Skills training

Question 26

Down Syndrome Adult Issues (3)

Answer 26

1. Transition
   a. Patient advocate and guide family during transition to adult care
   b. Group homes
   c. Facilitate transitionon: guardianship, financial planning, behavioral problems, school placement, vocational training, independence
   d. 12-14 start to plan when parents are not there
   e. Need to have very early discussion
2. Development of Intelligence
   a. Development comes to a halt in the teen years
3. Intellectual decline
   a. Higher incidence of early onset Alzheimer Disease; in 40s