Pediatric genetics Flashcards
(63 cards)
1
Q
Osteogenesis Imperfecta (“brittle bone disease”) is autosomal <u> </u> and involves what genes
A
- autosomal dominant
- genes alpha-1 and alpha -2 chains of type I collagen (COLA1 or COLA2)
2
Q
list the types of Osteogenesis Imperfecta
A
- Type I: Mild
- Type II: most severe (prenatal lethal)
- Type III-IX: moderate to severe
3
Q
Blue sclerae is indicative of
A
Osteogenesis Imperfecta
4
Q
clinical presentation
- short stature
- limb deformity
- scoliosis/kyphosis
- basilar skull deformity
- blue sclerae
- hearing loss
- opalescent teeth
A
Osteogenesis Imperfecta
5
Q
What imaging findings are consistent with Osteogenesis Imperfecta
A
- Wormian bones (suture bones)
- codfish vertebrae (compression fx)
6
Q
what labs should be done to evalulate for Osteogenesis Imperfecta
A
- biochemical testing: evaluate structure and quality of type I collagen
- labs: vit D, phosphorous, alk phosp may be elevated
7
Q
treatment of Osteogenesis Imperfecta
A
- Bisphosphonates-Pamidronate
- slows down bone resorption
- reduces fx rates and increases bone density
8
Q
adverse effects of Bisphosphonates-Pamidronate
A
- hypocalcemia
- osteonecrosis of jaw
- nephrotoxicity
9
Q
Marfan syndrome is autosomal . What gene is affected
A
- autosomal dominant
- FBN1 (fibrillin)
10
Q
What cardiac abnormalities are associated with Marfan’s syndrome
A
- aortic dissection
- mitral valve prolapse
11
Q
What pulmonary abnormalities are associated with Marfan’s syndrome
A
predisposed to spontaneous pneumothorax
12
Q
What ophthalmologic abnormalities are associated with Marfan’s syndrome
A
- myopia
- lens subluxation/dislocation
13
Q
clinical presentation
- tall, thin
- increased arm span/height ratio
- scoliosis
- arachnodactyly
- pectus deformity
- hindfoot valgus
- hypermobile joints with laxity
A
Marfan’s syndrome
14
Q
The steinberg sign
A
(A): positive if thumb tip extends from palm of hand
15
Q
The walker-Murdoch sign
A
(B) positive if thumb and fifth finger overlap
16
Q
How is Marfan’s syndrome diagnosed
A
- CVS or amniocentesis
- DNA testing
17
Q
Prader-Willi Syndrome is caused by
A
- spontaneous
- long arm of chromosome 15
- absence of paternal gene expression
18
Q
Prader-Willi Syndrome leads to dysfunction of
A
hypothalamus or pituitary
19
Q
what is genetic imprinting
A
expression of gene depends on gender of parent donating this gene
20
Q
loss of maternal copy of chromosome 15 results in
A
angelman syndrome
21
Q
Prader-Willi Syndrome can be due to either
A
- paternal deletion: 75% of cases
- maternal disomy
- two copies of chromosome 15 inherited from mother
22
Q
clinical presentation
- narrow forehead
- triangular mouth
- short
- depigmentation: skin and eyes
- hypogonadism
- intellectual delay
- food seeking behavior
A
Prader-Willi Syndrome
23
Q
This is characteristic of Prader-Willi Syndrome and is seen in infants and then changes in early childhood
A
- infants: profound hypotonia
- feeding difficulties
- early childhood: Hyperphagia and weight gain
- binge eating
24
Q
How is Prader-Willi Syndrome diagnosed
A
- molecular genetic test
- methylation analysis
25
Prader-Willi Syndrome is complicated by obesity which increases risk of
* type II DM
* Heart disease/stroke
* sleep apnea
* joint wear and tear
26
What is the most common inherited intellectual disability
Fragile X
27
Fragile X is due to what genetic abnormality? More severe in what patient population
* X linked recessive
* CGG repeated in FMR1 gene
* higher incidence/severity in males
* 90% are new mutations
28
Lyon hypothesis in females
* explains why the phenotypic effect of the X chromosome is the same in the mammalian female which has two X chromosomes as it is in the male which has only one X chromosome
* one of each two somatic X chromosomes in mammalian females is selected at random and inactivated early in embryonic development
29
clinical presentation
* intellectual impairment
* developmental delay
* autistic behaviors
* hyperactivity
* anxiety
* behavior/tantrums
* sz
Fragile X
30
Blue iris is associated with
Fragile X
31
What cardiac abnormality is associated with Fragile X
Mitral valve prolapse
32
clinical presentation
* soft smooth skin
* macrocephaly with prominent forehead and chin
* large ears and narrow face
* pes planus, hypotonia
* orchidism after puberty
Fragile X
33
Fragile X is associated with what 2 pre-mutations
* primary ovarian insufficiency (FXPOI)
* tremor/ataxia syndrome (FXTAS)
34
DiGeorge Syndrome is autosomal . What gene is affected
* autosomal **dominant**
* most often occurs randomly
* chromosome 22 defect: **22q11.2 deletion**
35
What is the classic triad of DiGeorge Syndrome
1. **Cardiac abnormalities**
2. **Hypoplastic thymus**: variable T-cell deficits
3. **Hypocalcemia**
* underdeveloped parathyroid
36
DiGeorge syndrome can also present with
* craniofacial abnormalities
* low set ears, wide set eyes, underdeveloped chin, bulbous nose tip
* cleft palate
* GU abnormalities
37
How is DiGeorge diagnosed
* **decreased CD3 + T cells + clinical findings**
* initial eval: urgent Echo
38
Complete DiGeorge syndrome has a life expectancy of . What is the tx for this patient
* less than 1 year without treatment
* Tx:
* thymic transplant
* HCT: hematopoietic cell transplant
39
What causes Klinefelter syndrome
47, XXY
40
clinical presentation
* **male**
* tall
* narrow shoulders
* microorchidism
* gynecomastia
* mild language delay and learning disability
Klinefelter syndrome
41
What levels of testosterone, FSH, and LH would you expect in Klinefelter syndrome
* testosterone low
* FSH/LH elevated
42
can males with Klinefelter syndrome have children
* 50% may be able to father a child with assistive technology
43
What causes Turner's syndrome
* females with 45, X
44
patients with Turner's syndrome are at a higher risk for
all X-linked recessive disorders
45
clinical presentation
* **female**
* short
* low hairline
* webbed neck
* broad chest with wide spaced nipples
* pigmented nevi
* streaked gonads
* amenorrhea
* Horseshoe kidney
* average intellect
Turner's syndrome
46
patients with Turner's syndrome have what cardiac abnormalites
* bicuspid AV (aortis stenosis)
* coarctation of aorta
* HTN
47
management of turner's syndrome
* infertility: IVF?
* estrogen and cyclic progesterone to stimulate puberty and assist with bone density
* monitor for gonadal malignancy
48
What is Patau syndrome
Trisomy 13
49
clinical presentation
* **cleft lip and palate**
* holoprosencephaly
* rocker bottom
* **CHD**
Patau syndrome
50
life expectancy of Patau syndrome
* majority die in utero
* \<5% survive beyond 6 months
51
defect in trisomy 13 is in
* prechordal mesoderm: midline craniofacial, eyes, forebrain
52
What is Edwards syndrome
* Trisomy 18
53
female to male ratio in Edwards syndrome
F:M = 3:1
54
clinical presentation
* intrauterine growth restriction with low birth weight
* hypertonia/spasticity
* horseshoe kidney
* omphalocele
* CHD
trisomy 18
55
Edwards syndrome is associated with what cardiac defects
* VSD
* PDA
56
prognosis trisomy 18
* majority die in utero
* 5% survive beyond 1 yr
* school age and adulthood is possible
57
What is down syndrome
Trisomy 21; most common chromosomal abnormality
58
what increases risk of Trisomy 21
advanced maternal age
59
clinical presentation
* open mouth
* protruding furrowed tongue
* CHD (50%)
* hypotonia
* joint laxity
* transverse palmar crease
Trisomy 21
60
can females with Trisomy 21 get pregnancy
yes, females are fertile
61
when should pregnant women be screened for Trisomy 21
* advanced maternal age
* following concerning features noted on US
* parenteral balanced robertsonian translocation
* previous h/o trisomy pregnancy
62
What screening tests are available
1. Triple test: AFP, hCG, unconjugated estriol
2. U/S
3. fetal karyotype
1. CVS: 1st trimester
2. amniocentesis: 2nd trimester
3. FISH
63
FISH: fluorescent in situ hybridization targets chromosomes
* 13, 18, 21, X, and Y
