Handbook of Genetic Counseling/Down Syndrome - Trisomy 21-2
Down Syndrome - Trisomy 21
Genetics
edit- 3 possible etiologies:
- Full trisomy 21 (95% of the cases)
- Due to nondisjunction during meiosis
- Usually maternal nondisjunction (90-95% of these cases)
- 75% of maternal nondisjunction occurs during meiosis 1
- 1% recurrence risk, unless the mother's age related risk is higher than 1%, in which case the age-related risk is quoted
- Unbalanced translocation (3-4% of cases)
- 50% of cases a parent carries a balanced translocation
- 50% of the unbalanced translocations are de novo and occur during fertilization
- Recurrence risk is 100% for a parental 21:21 translocation
- For a 21:14 translocation, recurrence is 16% if in the mother and 5% if in the father
- Mosaicism (1-2% of cases)
- Due to nondisjunction during mitosis, early in embryonic development
- Only cells that descend from that specific cell where nondisjunction occurred will be trisomy 21
- Usually associated with a less severe phenotype
- Full trisomy 21 (95% of the cases)
- Molecular Genetics
- Ongoing effort to define Chromosome 21 critical region
- Narrowed to 21q22
- DSCR1 is a candidate gene suspected to be involved in the pathogenesis of DS
Incidence
edit- One in every 650-1,000 children is born with down syndrome
Clinical Features
- Intelligence
- Mild to moderate mental retardation seen in most individuals (ranges from ~40-80)
- Language delays
- Cardiac
- >40% are born with congenital heart defects
- Av canal and VSD are common
- >40% are born with congenital heart defects
- Gastrointestinal
- Duodenal atresia is the most common
- Duodenal web (partial obstruction)
- Tracheoesophageal fistula
- Pyloric stenosis
- Omphalocele
- Hirschprung's disease
- Imperforate anus
- Annular pancreas
- Celiac disease
- Associations with vomiting, diarrhea, constipation, and feeding difficulties may be associated
- Auditory
- Recurrent otitis media
- Some degree of hearing loss is present in ~90% of patients
- Conductive hearing loss due to fluid accumulation
- Sensorineural hearing loss is also seen
- Craniofacial
- Macroglossia (60%)
- May cause feeding difficulty
- Dental malocclusions (100%)
- Constellation of characteristic facial features
- Brachycephaly
- Low nasal root, flat nasal bridge
- Epicanthic folds
- Small and occasionally overfolded ears
- Short neck sometime seen with redundant skin at the nape
- Brushfield spots
- Macroglossia (60%)
- Skeletal
- 14% have increased mobility of the cervical spine at the level of the 1st and 2nd vertebrae (atlantoaxial instability)
- other
- Respiratory problems can be due to midfacial hypoplasia which results in narrow airways
- Infections (recurrent croup due to narrow trachea)
- Obstructive airway disease
- Sleep apnea
- Leukemia
- Risk of developing leukemia is 15-30 times higher in Down syndrome patients than in the general population
- Hypothyroidism (15%)
- Common during adolescence
- Yearly monitoring of TSH and T(subscript)4 levels recommended
- Alzheimer's Disease
- 15% of adults with average age of onset ~50 yrs
- Eye problems
- Strabismus
- cataracts
- Seizures (5-10%)
- Correlation between age and prevalence
- Peaks at infancy and 4th-5th decade of life
- Short stature (average at 3rd percentile)
- Obesity
- Wide gap between first and second toes
- Hypotonia
- Clinodactyly of the 5th fingers
- Respiratory problems can be due to midfacial hypoplasia which results in narrow airways
Natural History/Prognosis
edit- Life expectancy has significantly increased
- No congenital heart defects: >60 yrs old
- Congenital heart defects: 30-35 yrs old
- Causes of death
- Leukemia (malignancy)
- Infections
Treatment and Management
edit- Echocardiograms, EKG, chest X-rays to monitor heart defects
- Surgery may be required
- Ophthalmology exams
- Hearing exams
- Abdominal X-rays, barium swallow or enema to follow digestive problems
- TSH levels to detect hypothyroidism
- Early intervention for MR and developmental delays
- Physical therapy for gross and fine motor skills
- Speech therapy
References
edit- Jones KL (1997). Smith's Recognizable Patterns of Human Malformation. Philadelphia: W.B. Saunders Company
- Jorde LB, Carey JC, Bamshad MJ, White RL (1999). Medical Genetics. 2nd ed.
Philadelphia: Mosby.
- Cohen WI (1999). Health Care Guidelines for Individuals with Down Syndrome: 1999 Revision (Down Syndrome Preventive Medical Check List). Down Syndrome Quarterly.
- Web References: OMIM Entry #190685
Notes
editThe information in this outline was last updated in 2000.