DOWN SYNDROME and OTHER TRISOMIES

DOWN SYNDROME     in humans, the most common abnormality of autosomal chromosomes trisomy 21 80-90% nondisjun...

DOWN SYNDROME

 

 

1. in humans, the most common abnormality of autosomal chromosomes
2. trisomy 21
   • 80-90% nondisjunction
   • 5% translocations
   • 3% mosaics (may be less noticeable/less severe) 
3. incidence: most common autosomal chromosomal abnormality,
   • 1 in 600-800 live births
   • rises with advanced maternal age to 1 in 20 by age 45 years
4. affected fetuses have increased risk of spontaneous abortion

Clinical features

1. hypotonia at birth (80%), low IQ, developmental delay
2. neurologic: hypotonia, premature senility, Alzheimer’s onset in 40’s
3. facies: flat occiput, microcephaly, small midface, small mandible and maxillae, upslanting palpebral fissures, epicanthal folds, Brushfield's spots in iris
4. ENT: furrowed prominent tongue, high arched palate, ear anomalies, frequent acute otitis media
5. CVS: 40% have congenital cardiac defects, particularly endocardial cushion defects
6. GI: duodenal, anal atresia and TE fistula
7. MSK: lax joints including dysplastic hips, vertebral anomalies, atlantoaxial instability
8. skin: Simian (palmar) crease, abnormal dermatoglyphics
9. hematologic: leukemias (1% lifetime risk)
10. endocrine: hypothyroidism 

prognosis: shorter life expectancy 

 

Management

1. recommended testing: echo, thyroid tests, atlanto-occipital
   x-ray at 2 years (controversial)
2. treat any life-threatening defects immediately
   (e.g. duodenal atresia)
3. mainly symptomatic
4. wide range of severity, early intervention programs to help
   children reach full potential

OTHER TRISOMIES

Trisomy 13

 

1. incidence 1:5000 live births
2. increased risk of spontaneous abortions
3. features: seizures, deafness, microcephaly, cleft lip/palate,polydactyly, retinal anomalies, single umbilical artery, cardiac defects, scalp defects
4. midline anomalies: scalp, pituitary, palate, heart, umbilicus, anus
5. prognosis: 44% die in 1 month
   
   

Trisomy 18

 

1. incidence: 1/8000 live births, female: male = 3:1
2. increased risk of spontaneous abortion
3. features: prominent occiput, micrognathia, ocular abnormalities, cleft lip and palate, low set ears, rocker bottom feet, short stature, clenched fist with overlapping digits, hypoplastic nails, clinodactyly, polydactyly,cardiac defects, hernia, severe CNS malformation, urogenital abnormalities (cryptorchidism, polycystic kidneys)
4. key point: small babies (SGA, microcephaly, short)
5. prognosis of severe FTT: 33% die in 1 month, 50% by 2 months, 90% by 12 months, profound MR in survivors