Down Syndrome Flashcards
Causes of Down Syndrome
95% of cases
Trisomy 21
i.e. parents have normal chromosomes
If Down Syndrome results from Trisomy 21, where the parents have normal chromosomes, what is the recurrence risk?
1/100 + risk of maternal age
What is responsible for the minority of Down Syndrome cases (3-4%)?
Unbalanced translocation between chromosome 21 and another acrocentric chromosome
Which are the acrocentric chromosomes?
13, 14, 15, 21, 22
If Down Syndrome is due to unbalanced translocation, what becomes exceedingly more important?
To check karyotype of parents
What is the least common type of Down Syndrome?
Mosaic Trisomy 21 (mixture of normal and cells containing 21)
1-2% patients
Phenotype tends to be more mild
DS
Prenatal counseling
What causes DS?
What increases risk?
Error of Nondysjunction
Increasing risk with maternal age
DS
Prenatal screening
1st trimester
Ultrasound measurement of nuchal folds + beta-hCG + PAPP-A
(pregnancy associated plasma protein A)
Detection rate - 82-87%
DS
Prenatal screening
2nd trimester
quad screen
- beta-hCG
- AFP (alpha-fetoprotein)
- unconjugated estriol
- inhibin level
Detection rate = 80%
DS prenatal screen
The 1st trimester screen usually has a 82-87% detection rate, and the 2nd trimester screen usually has an 80% detection rate; what do they have combined?
95%
If you suspect DS based on 1st or second trimester screening, how can you confirm?
By chromosome analysis via amniocentesis or CVS (chorionic villus sampling)
DS and Cell free DNA
Screens maternal serum for fetal cells - not perfect - false positive and false negatives associated with this screen
DS (Trisomy 21) is the most common chromosomal abnormality seen in liveborn infants, what is it’s estimated incidence?
1/700 births
What three kinds of trisomy may be seen in liveborn infants?
13, 18, 21
Is trisomy 21 the most common chromosomal abnormality
No! Not if you are being picky about the wording… it is not the most common chromosomal abnormality but it is less life threatening than abnormalities that cause pre-term death, thus it is the most common in birth
Features of infants with DS
Common physical features at birth
Are growth parameters abnormal?
No, growth parameters are usually normal
DS physical features @ birth
ENT and Eyes
midfacial hypoplasia (small midface)
upslanting palpebral fissures
epicanthal folds (skin covering inner corner eyelid)
small ears
large appearing tongue (too small compartment)
DS physical features @ birth
Muscles and appendages
low muscle tone, increased joint motility
short fingers, transverse palmar crease, Vth finger incurving (clinodactyly), increased space between toes 1 and 2
DS Common Medical Issues
Cardiac Issues
Seen in approximately 50%
All types of anomalies may be present but AV canal is common
Echocardiogram in the newborn period is recommended
DS Common Medical Issues
Gastrointestinal
Infants
10-15% of infants have structural anomalies
Esophageal atresia - esophagus end in blind ended pouch rather than connecting to stomach
Duodenal atresia - closure of a portion of the lumen of duodenum
Hirschsprungs - ganglion cells of intestine absent - inhibited paristalsis
DS Common Medical Issues
GI in Children
Feeding Problems - very common
Constipation - very common
GERD - Very common
Celiac Disease - recommended screening is TTG + IgA
DS Common Medical Issues
Ophthalmologic
Blocked tear ducts - can lead to conjunctivitis
myopia
lazy eye
Nystagmus
Cataracts - may present in newborn or infancy
Nystagmus -
repetitive uncontrolled movements of the eye
What ophthalmologic test is imporant for DS in infancy?
Light Reflex
DS Common Medical Issues
ENT
Chonic ear infections
Deafness - both sensorineural and conductive
Chronic nasal congestion
Enlarged tonsils and adenoids
Consequence of enlarge tonsils and adenoids in DS?
Obstructive apnea - preschool age is common time to present with this problem - also issue in older children who develop obesity
Down Syndrome
Endocrine and Autoimmune Problems
Thyroid disease - most commonly hypothyroidism (1/4 but adolescence), which may be congenital or acquired
Insulin dependent diabetes
Alopecia Areata
Reduced fertility (but normal puberty)
Can DS have babies?
Not males
Rare instances females
DS Orthopedic Problems
Hips
Joint subluxation
Atlantoaxial subluxation
subluxation = incomplete or partial dislocation
DS Hematologic Issues
Myeloproliferative disorder in the newborn (looks preleukemic)
increased risk for leukemia - 12-20x
iron deficiency anemia - usually attributable to feeding deficiencies
DS Developmental Issues
Hypotonia effects gross motor development (baby walks @1 DS baby walks 2-5)
Spectrum of intellectual disability - average is mild moderate disabilities
Speech problems
- importance of sign language
What do we mean when we say mild intellectual disability in DS?
Average IQ about 50
DS Neurologic Problems
Hypotonia - spectrum from mild to severe
Seizures, especially infantile spasms
DS Psychiatric issues
Depression
Early Alzheimer’s
Autism 1/10 patients
DS transition to adult care issues
Adult providers suck (basically)
DS and independence
Independence and self help skills is sometime more important than academic
Appropriate social skills can be taught
Communication skills are key to success
Patient should try to learn main disabilities / problems / medications / allergies
DS and Genetic Research
“Down Syndrome Region” on chr21q
Mouse model - chromosomes 16 and 10 (similar behavior to 21 in humans)
Down syndrome and autism: why does this happen?
Increased incidence of autoimmune disorders
