peds: genetics Flashcards
chromosome nomenclature
total #, XX (or XY) del(+) (# ) (r(q)#)
r/q # is the band on that chromosome
eg 46XXdel(14)(r23)
47XY +21
chromosome structure
cells contains ___ chromosomes (___ pairs)
structure
p & q arms
- cells contain 46 chromosomes, 23 pairs
- pair of chromatid, joined by centromere
- p short arm on top
q long arm on bottom
types of structural abnormalities (4)
- deletions: portion of or entire chromosome missing
- duplications: a portion of chromosome is duplicated => extra genetic material
- translocations: a portion of 1 chromosome is transferred to another
- inversions: a portion of chromosome has broken off, inverted and reattached => inverted genetic material
numerical abnormalities
sciency word
and sciencey word for too many and too few
aneuploidy= wrong # of chromosomes
monosomy = missing a chrom trisomy = an extra one in the pair
global developmental delay (GDD) def
delay in achieving 2 or more developmental milestones; motor, speech, cognition, social or emotional
non-disjunction error def and when does it occur in cell reproduction type of chromosomal abnormality
def: when entire chromosome or sister chromatids dont separate and => different cells; occurs most commonly in older cells during meiosis or mitosis
=> numerical abnormality
autosomal trisomy
type of error
associated with…
most common disease (2)
non-disjunction error
associated with advanced maternal age
#1= trisomy 21 = downs syndrome trisomy 18 = edwards syndrome
2 most common sex chromosome aneuploidys
cause
- turners syndrome = 45X
female missing part or all of an X chrosome - Kleinfelter Syndrome = 47XXY
male has an extra X chromosome
these are both caused by non-disjunction errors
Turners syndrome
chromosome name
some of the most common symptoms (5)
dysmorphic features
45X
dysmorphic features short webbed neck, puffy hands and feet, short stature
- usually 1 kidney => can’t play contact sports*
- hypothyroidism => delayed growth (usually short)
- lack estrogen => absent sexual develoment and osteoporosis
- frequent middle ear infections* => developmental delays
- visual spatial defects
Kleinfelter syndrome
chromosomal name
3 symptoms
47XXY
- learning disabilities
- frequent inner ear infections => speech and language delay
- poor coordination
4 most common diseases associated with structural abnormalities
- Cri-du-chat - deletion chromosome 7
- williams syndrome - deletion chrom 7
- prader willi syndrome - deletion chrom 15
- angelman syndrome - deletion chrom 15
Cri-du- chat symptoms (7)
and dysmorphic features
caused by du novo deletion of chrom 7
- cat like cry*
- hypotonia & low birth weight; failure to thrive
- MR mod -> severe; microcephaly
- stabismum
- self injurious
- scolosis
- congenital heart defects
dysmorphic features: large mouth & microcephaly
Prader - Willi syndrome
common symptoms (7)
dysmorphic features
from du Novo deletion chrom 15
- respiratory difficulties
- poor suck/swallow reflex at birth => failure to thrive and later children become obese and obsessed with food
- sleep apnea => day time drowsniess
- low -> mod MR; GDD
- strabismus
- poor motor coordination
- behavioral issues; stubborn, tantrums, physical agression
dysmorphic features= short, small hands/feet & narrow face
angelman syndrome
cause
common symptoms
dysmorphic features
deletion chrom 15 from mother
symptoms:
1. seizures starting at 2-3
2. tremors
3. hypotonia/ GDD
4. expressive language more impaired than receptive => use sign language
5. wide base ataxic gait with jerky movements
6. ADD/ADHD
7. inappropriate happy affect with episodes of laughing** tell tale sign*
this is how you know its not autism
dysmorphic features; microcephaly & large mouth
Williams syndrome
cause
symptoms (5)
deletion chromosome 7
- CV disease* => HTN (so be aware when exercising)
- RU fused => limited pro/supination
- mild cognitive impairment => ADHD
- delay with speech/ fine & gross motor skills
- visual spatial difficulties
4 types of single gene disorders
- autosomal dominant; only need one parent to have
- autosomal recessive; both parents must have gene but usually no family Hx
- X-linked recessive; female carries, but only males affected
- mitochondrial disorders
3 examples of autosomal dominant disorders
- osteogenesis imperfecta
- congenital myotonic dystrophy
- neurofibromatosis (NF1)
NF1 von recklinghausen
pathophysiology (2)
signs (1)
symptoms (7)
(neurofibromatosis)
- gene which encodes neurofibromin, which is a tumor supressor by keeping cells from growing or diving too rapidly
- mutations of this gene => tumors all over body
signs: cafe au lait spots on skin, >6 or larger than a quarter
symptoms:
- skeletal abnormalities, short with scolosis & long bone nonunion
- decreased bone mineral density => cant do contact sports
- optic glioma => vision loss by age 4
- pectus excavatum
- learning disabilites, ADHD
- poor coordination & clumsy
- hypotonia
biochemical disorders def (2)
- metabolism errors caused by metabolic enzyme deficiencies
2. enzyme absent or not working properly => neuromotor / musculoskeletal deficits
2 biochemical disorders
- phenylketonuria - part of newborn screen, looks for elevated metabolites
- lysosomal storage disease => accumulation of undegraded materials in lysosome
eg tay-sachs & gauchers
2 examples of X-linked recessive disease
- hemophilia
2. duchenne muscular dystrophy
X-linked dominant
2 diseases
- fragile-X
2. Rhetts syndrome
fragile X syndrome
pathophys
symptoms (6)
mutation on FMR1 gene on X chromosome => doesn’t synthesize chemical needed for proper brain development
symptoms
- GDD by 2 years
- intellectual disability
- autism spectrum
- SZ
- poor coordination, balance, motor planning
- hyperextensible joints
Rhetts syndrome pathophys dx who it affects symptoms rhetts vs. autism
mutations on MeCP2 gene on X chromosome which regulated proteins involved with brain development
dx is a blood test
almost exclusively affects females
development is normal in early infancy until the MeCP2 regulation is needed, then develop backwards
often misdiagnosed for autism but these girls are more interested in people than objects
Rhetts diagnostic criteria (3)
- normal development until 6-18m
- slowing of head growth rate at 2-4 months (=> MR)
- gait abnormalities & sterotypic hand movements*- ringing hands
rhetts syndrome stages I-IV symptoms & ages at each stage life expectancy stage I stage II (4) stage III (4) stage IV (5)
stage I- 6-18 months
subtle slowing of development & less eye contact
stage II = rapid loss of acquired skills, ages 1-4
- autistic behaviors; loss of spoken language and social skills
- hand wringing
- slow head growth => microcephaly (and MR)
- gait abnormalities wide BOS, ataxic & toe walking
stage III = plateau; pre-school - school age (2-1)
how most girls stay the rest of their lives
1. SZ
2. apraxia (=> motor difficulties)
3. hyperventilation & breath holding
4. communication skills may improve
stage IV = motor deterioration
- reduced mobility
- muscle weakness
- rigid spasticiy dystonia
- NM scolosis
- osteoporosis risk
life expectancy ~4-
mitochondrial disorders
pathophys
who we get them from and why
parts that are most affected (2) & why
- alteration in mitochondrial DNA fragments inherited from mother
- only from mother because zygote gets all of its mitochondria from the egg
- CNS and muscle affected because of large amts of mitochondria in tissue
clinical features of mitochondrial disorders (4)
- myopathies of general weakness & decreased balance
- exercise intolerance
- encephalopathy
- retinal degeneration
multifactorial disorders
def
2 examples
- combination of genetic and environmental factors
eg
- birth defects = cleft palate
- adult onset = cancer
4 diseases pectus excavatum is associated with
- MVP (mitral valve prolapse)
- scolosis
- marfans
- NF1 von Recklinghausen
4 diseases (or categories) hypotonia is associated with
- genetic syndromes (eg downs syndrome)
- neurological diseases (eg CP)
- metabolic diseases
- endocrine disorders
3 characteristics of failure to thrive
- weight < 3rd-5th % for age
- progressive loss of weight to <3rd-5th %
- decrease in % for height & weight in short amt of time
