What is the chromosomal error that cases trisomy 21 and what increases the risk of this happening?
Error in nondisjunction
Maternal age ≥35-40
What are the three genotypes associated with DS and what percentages of pts present with each?
Trisomy 21 95%
Unbalanced Translocation 3-4% (e.g. t(21,14))
Mosaic Tri 21 1-2% milder presentation usually
First trimester screening for Trisomy 21?
Ultrasond measrement of nuchal folds (extra folds = bad)
Beta-hCG + PAPP-A
(human chorionic gonadotropin, pregnancy-associated plasma protein A)
2nd trimester trisomy 21 screening?
Detection rate in 2nd trimester?
Quad Screen beta-hCG AFP (alpha-fetoprotein) unconjugated estriol inhibin level
Detection rate at 2nd trimester = 95%
Estimated incidence of trisomy 21?
1 in 700
At what maternal age is the risk become high?
35 and up the curve shoots up.
1/100 + maternal age risk (see graph)
age 40 risk is 1/100
—> recurrance risk is 1/50
List some common physical finding of a DS infant.
- growth parameters usually normal
- midfacial hypoplasia
- upslanting palpebral fisures, epicanthal folds
- small ears
- tounge seems large but really the oral compartment is small
- low muscle tone (hypotonia), double jointed (increased joint mobility)
- short fingers, transverse palmer crease, 5th finger incurving (clinodactyly), increased space btwn 1st & 2nd toes
- Eustation tubes too small -> ear infections
Incidence of cardiac issues in DS pts?
Some common cardiac issues?
50% of DS pts have cardiac issues
Wide range of cardiac defects:
Atrioventriclar Canal (common, needs surgical repair)
hole btwn atria
hole btwn ventricles
Incidence of GI tract issues in DS pts?
3 most common ones?
10 - 15% of infants have GI tract structural anomalies
Hirschsprng’s Disease (sympathetics non-functional in lower 1/3 of bowel, constipation)
What are the functional GI issues in DS pts?
feeding problems - very common
constipation - extremely common due to hyptonia
GERD - very common
Celiac Disease (screen with TTG +IgA)
What are the opthalmologic problems in DS pts?
blocked tear ducts myopia (near sightedness) strabismus (lazy eye) nystagmus cataracts - congenital or dev. over time
What fraction of DS pts have ear, nose and throat problems?
Common ENT problems?
chronic ear infections (small eustatian tubes)
deafness (both conductive (fluid) and sensorineural)
chronic nasal congestion
enlarged tonsils & adnoids = Obstructive Sleep Apnea, also related to obesity
What are some common endocrine disorders in DS pts?
Thyroid = most common endocrine problem seen; usually hypothyroidism but also Grave's disease Insulin Dependent Diabetes (type 1) Alopecia Areata (hair falls out in patches) Reduced fertility
Joint issues in DS pts?
**atlantoaxial subluxation - rare but bad = high level cervical paralysis
Hematologic Issues in DS pts?
Myeloproliferative disorder in newborns
increased risk of leukemia - 12 to 20 times
iron deficiency anemia
Developmental Isses in DS pts?
hypotonia = gross motor activities affected
intellectual disabilities - average is mile-moderate disabilities (50 IQ)
Speech problems - poss. due to hypotonia; tongue not fit in mouth or hearing issues or some comb. of the three
use sign language
Neurologic issues in DS pts?
hypotonia - mild to severe possible
seizures - especially infantile spasms
Psychiatric Issues in DS pts?
Autism 1 in 10 pts