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Common chromosomal disorders :post_office: (:dango: Down syndrome (:film…
Common chromosomal disorders :post_office:
Basic molecular genetic
One chromosome
Cell division & Cycle
Mitosis
Meiosis
Meiotic nondisjunction
First
meiotic division
After combine with haploid gamete results in offspring of
Trisomic
x 2
Monosomic x 2
Second
meiotic division
After combine with haploid gamete resulting in
Disomic (normal) x 2
Trisomic
Monosomic
:star: assoc. with Advanced maternal age
Chromosomal disorders
Common chromosome disorders
Autosomal
abnormalities
:dango:
Trisomy 18 (Edwards Syndrome)
:dango:
Trisomy 13 (Patau Syndrome)
:dango:
Down syndrome
Sex chromosome
abnormalities
:peach:
Klinefelter syndrome
:peach:
Turner syndrome
47, XYY syndrome
Trisomy X (47, XXX)
:koala:
Types
Numerical abnormalities
Aneuploidy
Def: :arrow_up: or :arrow_down: in Diploid no.
assoc. with Advanced maternal age
Autosome
Trisomy 47, XX + 13/18/21 (:dango:
Trisomy ต่างๆ)
Sex chromosome
:peach:
Klinefelter
47, XXY
Monosomy 45 X
Polyploidy
Def: Multiple of the haploid no. (23)
eg. Triploidy 69,XXY — mostly
nonviable
usually present with Abortion
Structural abnormalities
:grapes:
:sunflower:
Robertsonian translocation
Long arm of
2 Acrocentric chromosome fuse near the centromere
Loss of short arm
Karyotype has
only 45 chromosome
Normal phenotype
:arrow_up: risk of Abortion & Unbalanced Abnormal offspring
I/C for Chromosome study
:check:
Genetic disorders
:grapes:
Chromosomal
disorders —
0.6%
of live births
Single gene
disorders —
1.2%
of live births
eg. G6PD def
Multifactorial
disorders: Environment + Genetic
eg. cleft lips cleft palates
Somatic
cell mutation: Malignancy
Others
Microdeletion
syndrome
eg. DiGeorge syndrome
Mitochondrial
disorders
Imprinting
disorders
:dango:
Down syndrome
:pig2:
Causes
Trisomy 21 (95%) (47,XX/XY, +21)
result fr Nondisjunc (90% fr mom)
Translocation (4%)
result fr
Robersonian translocation
between 21q & another acrocentric chromosome
➯ need to do
chromosome study
on
BOTH parents
Mosaic (1%)
each cells express itself differently
:frame_with_picture:
Dysmorphic features
HEENT: Brachycephaly, Flat facial profile, Upward slanting palpebdal fissure, Short neck&redundant skin
Skin & Ext: Simian crease, Hypoplasia of middle phalanx of 5th finger, Widening of 1st web space of toe
:film_frames:
Associated anomaly
:<3:
Cardio 40-50%
: CAVC, VSD, ASD, PDA, TOF
:shallow_pan_of_food:
GI 10-15%
: Duodenal atresia, Hirschspung ds
:necktie:
Thyroid
: Hypothyroid 15-30% at any age, Autoimmune thyroidits
:eye:
Eye
: Refractive error, Strabismus 60%
:ear::skin-tone-2:
Ear
: Hearing loss 60%
:meat_on_bone:
Atlantoaxial subluxation
or
instability
15%
:red_circle:
Hemato
: Transient proliferative disorder 10%,
Leukemia 1%➯ <3 yr — AML; >3 yr — ALL
Hypotonia
Frequent respiratory tract infection due to Low muscle tone, Abnormal eustachian tube & decrease B&T cell function
Developmental delay
:green_apple:
Rx
Genetic counseling & Familial support group
Early stimulation program
Treat CHD, hypothyroidism
Quadruple screening (
rec. in mother > 35 yr
)
:arrow_down: AFP, Estriol
:arrow_up: β-hCG, Inhibin-A
Amniocentesis is the next
:heartpulse:
Health supervision
:grapes:
:<3:
CHD
: Echo at Birth
:shallow_pan_of_food:
GI
: by
Clinical at birth
:necktie:
Thyroid
:
TFT
birth,
6-12mo
then yearly
:eye:
Eye
:
birth-6mo.
then yearly by Ophthalmologist
:ear::skin-tone-2:
Ear
: ABR or OAE
birth-3mo.
then
q 6 mo.-1 yr
then
yearly
Note: ABR = Auditory Brainstem Response, OAE = Otoacoustic emissions
:red_circle:
Hemato
: CBC
birth
and
adolescent
or
if symptomatic
:meat_on_bone:
C1-C2 subluxation
: Film
3-5yr
or
when plan contact sport
or
symptomatic
:sleeping_accommodation:
OSA
:
1yr
& each visit
:station:
Recurrence risk
Trisomy 21:
1%
risk of DS in pregnant woman at specific age
15%
in mom who is Balanced translocation carrier &
5%
in dad
100%
in parent with
Balanced translocation of t21;21
:dango:
Trisomy 13 (Patau syndrome)
:frame_with_picture:
Clinical pictures
Small for GA (SGA)
Profound Mental retardation (MR)
Microcephaly, CNS abnormalities:
Holoprosencephaly (50%)
HEENT:
Head: Scalp defect, Microcephaly
Ear: ~
Eye: Microphthalmia (ตาเล็กๆ), Eye anomalies
Mouth: Cleft lip/Cleft palate
Nose: Bulbous nose
Hand: Clenched hand, Postaxial polydactyly
Feet: Rocker bottom feet, Postaxial polydactyly
Heart:
Congenital HD 80-90%
:heartpulse:
Urogenital defects
: Cryptorchidism (ไข่ไม่ลงถุง), Bicornuate uterus, Hypoplastc ovaries, Polycystic kidney
Omphalocele
90%
died
within 1 yr old
:pig2:
Causes
Trisomy 13:
90% assoc. with advanced maternal age
Unbalanced translocation
5-10%
➯ need to do
Chromosome study
on
both parents
Mosaic
1%
:station:
Recurrence risk
Trisomy 13:
1%
Higher if 1 of the parents is Balanced translocation carrier
:dango:
Trisomy 18 (Edwards syndrome)
:earth_asia:
Incidence
1:8,000 live births
:female_sign: > :male_sign: =
3
: 1
70% deaths are due to
Cardiopulmonary arrest
Central apnea
— commonly seen in NB period
:frame_with_picture:
Clinical pictures
Small for GA (SGA), spasticity
HEENT:
Head: Microcephaly, Prominent occiput, Micrognathia
Ear: Low set ears or Malformed ears
Eye: Microphthalmia (ตาเล็กๆ), Eye anomalies
Mouth: Cleft lip/Cleft palate
Nose: Bulbous nose
Hand: Clenched hand
Feet: Rocker bottom feet
Heart:
Congenital HD 90%
:heartpulse:
Survives to 1 wk only 45%,
to 6 mo. just 9%,
to 1 year 5%
Chest: Short sternum
:pig2:
Causes
Trisomy 18:
assoc. with advanced maternal age
Unbalanced translocation ➯ need to do
Chromosome study
on
both parents
Mosaic
:station:
Recurrence risk
Trisomy 18:
0.65 - 1%
Higher if 1 of the parents is Balanced translocation carrier
:green_apple:
Mx
Quadruple screening
:arrow_down: AFP, Estriol, β-hCG
:peach:
Turner syndrome
:earth_americas:
Incidence
1: 2,000
female
live births
Spontaneous abortion > 99%
:frame_with_picture:
Clinical pictures
Infant
:baby::skin-tone-3:
Lympedema of hand & feet
Cystic hygroma
Short 4th-5th metacarpal & metatarsal bones
Childhood
:children_crossing:
Short stature
Webbed neck
Chest: Windely spaced nipple, Broad shield chest
Cubitus valgus (not seen 100% tho)
:film_frames:
Associated anomaly
:heartbeat::
CHD 40%
: Bicuspid aortic value (
1st
), COA (
2nd
)
:horse::
KUB 60%
: Horseshoe kidney
:necktie:
Thyroid
: Autoimmune thyroidits
:ear::skin-tone-2:
Ear
: Recurrent otitis media ➯ frequently? ➯ Sensorineural hearing loss
Gonadal
agenesis: Delayed puberty, infertility
Normal intelligence :) (tho can hv LD - learning disorder in some)
:heartpulse:
Health supervision
:heartbeat:: check BP & peripheral pulse, compare arm & leg SBP, consult cardiologist
:horse:
KUB 60%
: U/S KUB if abnormal monitor UTI & renal func.
:necktie:
Thyroid
: test
after age 4 yr
then
q 1-2 yr
:ear::skin-tone-2:
Ear
: NB hearing screening ➯ then check for serous otitis & otitis media on every visit ➯ later hearing test
6mo.
and
12mo.
Consider
Estrogen replacement therapy
when
reaches pubertal age
Feeding problem
: due to impaired oral motor func
Congenital hip dysplasia examination
in infant
Scoliosis
check yearly in late childhood
:eye:
Eye
: exam for Strabismus
F/U growth & consult endocrinologist for GH therapy
usu.
starts
after Height fall < P5
➯ can :arrow_up: final adult height up to 8-10 cm
Check for
developmental delay
&
learning disorder
esp. before enter school
Genetic counseling
:peach:
Noonan syndrome
AD, affected both sexes
:frame_with_picture:
Clinical like Turner-liked phenotype
Short stature
Low posterior hairline
Webbed neck
Shield chest
:film_frames:
Assoc. anomaly
:heartpulse:
CHD
typically involving
Rt-sided lesion
eg PS, ASD secundum, Hypertrophic cardiomyopathy
:pig2:
causes
Multiple gene multations can cause Noonan
:peach:
Klinefelter syndrome
47, XXY
:pig2:
Causes
Maternal meiotic error 50% (assoc. with advanced maternal age)
:frame_with_picture:
Clinical pictures
Taller > average long arm & legs
Gonads: Small testes, infertile, 1/3 gynecomastia
infertile = found in SI not success or SI success but no child
10-15 IQ point lower than siblings