I. EPIDEMIOLOGY

Maximal trisomy 21 births from mothers aged:

• 28 yrs (but this is only because the maximal birth rate is for this maternal age).
  
• Around 37 yrs.
  
• The risk increases with maternal age: <0.1% below 30 yrs; between 0.1% and 1% at ages 30-40 (0.2% at 34 yrs, 0.5% at 38 yrs, 0.7% at 39 yrs); >1% above 40 yrs (5% at 46 yrs, 15% at 50 yrs).

II. CLINICAL EXAMINATION

• evocative face +++:
  
  
  • frequent microcephaly, short neck, flat occiput and brachycephaly;
    
  • moon-shaped face;
    
    
  • flat nasal bridge;
    
  • "socket" nostrils;
    
    
  • hypertelorism (or pseudo-hypertelorism);
    
  • epicanthus (regresse with age);
    
  • upward slanting palpebral fissures;
    
  • Brushfield spots in the iris (pathognomonic, detectable in blue eyes).
    
    
  • macroglossia; glossitis exfoliativa (geographic tongue); scrotal tongue at late childhood and in adulthood;
    
  • mouth frequently open; frequently open mouth;
    
  • narrow/ high arched palate; high arched narrow palate;
    
  • late appearing/malformed teeth (numerical anomalies, agenesis of lateral incisors...);
    
  
  
• hands and feet:
  
  • short and broad;
    
  • brachymesophalangia of the 2nd and 5th fingers;
    
  • clinodactyly of the 5th finger;
    
  • flat feet;
    
  • first toe set apart from the others by a gap, with a crease.
  
  
  
• dry skin, mottled skin (livedo), with frequent infections around orifices.
  
  
• hyperlaxity of ligaments.
  
• frequent umbilical hernia.

• hypotonia +++ at birth (hold his head at 6 mths, sits at age 1 yr, walks at age 2 yrs).
  
• the mental retardation, not obvious in the infant, will soon become manifest.
  
• children's behaviour:
  
  • affectionate, gentle, cheerful;
    
  • language difficulties;
    
  • like to play, to mime, to tidy up meticulously;
    
  • normal memory.
  
  
• seizures (in 3% to 9%, as compared to 1% in the general population).

• transverse palmar crease in 75% of cases. Beware: it is also present in 1% of the general population; therefore, out of 8 transverse palmar creases at birth, 7 come from the general population and only 1 from a Down syndrome baby (1% risk X 699/700 births versus 75% risk X 1/700 births): one MUST NOT make a diagnosis of trisomy 21 on this isolated sign and throw parents into a panic.
  
• axial triradius in t" (in 75%).
  
• transversality index > 30.

• Heart (40%):
  
  • atrioventricular septal defect (10 %);
    
  • ventricular septal defect (10 %);
    
  • patent foramen ovale (5 %);
    
  • persistence of ductus arteriosus (5 %)...
  
  
  
• Digestive (10 %):
  
  • duodenal stenosis (1/3 of duodenal stenosis are found in trisomy 21patients);
    
  • imperforate anus...
    
  
  
• Ocular:
  
  • cataract (congenital or acquired);
    
  • astigmatism;
    
  • myopia;
    
  • strabismus;
    
  • congenital glaucoma;
    
  • nystagmus.
  
  

• Hematologic:
  
  • ³transient leukemoid reaction² may occur
    
  • sometimes with a relapse as acute leukemia (lymphoblastic (ALL) or more frequently non-lymphoblastic (ANLL) leukemias; M7-ANLL (megakaryocytic) is particularly frequent. Watch the hypersensitivity to methotrexate.
  
  
  
• Immunological:
  
  • tuberculine hyporeactivity;
    
  • immune deficiency.
  
  
  
• Metabolic:
  
  • hyperuricemia;
    
  • abnormal glycemia;
    
  • increased TSH (frequent); hypo or hyper thyroidy.
  
  

III. DIAGNOSIS: THE KARYOTYPE

• sporadic (de novo) cases.
  
• role of maternal age (see above in epidemiology).
  
• recurrence risk: 1 to 2 %.
  
• karyotype: 47,XY,+21 ou 47,XX,+21.
  
• due to meiotic non-disjunction:
  
  • of maternal origin:
    - lst division: 70 %
    - 2nd division: 20 %
    
  • of paternal origin:
    - lst division: 5 %
    - 2nd division: 5 %
  
  

• sporadic cases.
  
• karyotype: 46, XY / 47, XY,+21 or 46, XX / 47, XX,+21.
  
• post zygotic event (mitotic).
  
• most often, the phenotype is typical, at times attenuated.

• de novo or transmitted from a parental translocation (being a balanced translocation in the parent); genetic coonseling is especially needed in the latter case.
  
• karyotype with 46 chromosomes; the extra chromosome 21 is most often translocated with another acrocentric (groupe D: 14, 13 or 15 or groupe G: 21 or 22) chromosome; example: 46, XY, t(14;21).
  
• genetic counseling and recurrence risk:
  
  • t(Dq;21q) et t(21q;22q)
    
    of maternal origin: risk = 15 %
    of paternal origin: risk = 5%
    
    
  • t(21q;21q): risk = 100 %:
    
    either --> trisomy 21
    or --> spontaneous miscarriage (monosomy 21).
    
    
    
  • Other:
    
    • partial trisomy 21 (rare). -->(the segment responsible for most of the syndrome/phenotype is band 21q22.3.
      
    • associated with other chromosome anomalies (rare).
    
    
    
    

IV. EVOLUTION

• statural delay (adult = 1,50 m); weight excess (--> diet).
  
• voice becomes hoarse.
  
• pelade may appear.
  
• puberty is delayed but normal; poor libido;
  
• fecondity in the female ( --> contraception).
  
• hypothyroidy, Basedow (--> T3, T4, TSH, reverse T3 regular determination).
  
  
• mental development:
  
  • intelligence quotient (IQ) = 50 (mean (and median)); between 30 and 80; Gaussian curve, as in the general population but with a mean shift to 50 instead of 100; vary according to age);
    
  • social insertion: partly according to the familial environment, the guidance and reassurance that the family receives, and according to the medical, paramedical, and pedagogic cares instaured;
    
  • psychomotor therapy from the age of 6 mths, kinesitherapy, orthophony latter; nursery school, followed if possible by a class of handicapped children within a normal primary school; latter, school and professional school in specialized institutions; apprenticeship, manual professionnal activity; insertion into active life; they must not stay at parents home, where they would remain with a child status, and finally where they would grow old faster as parents get old.
  
  
  
• early aging:
  
  • behaviour may suddenly switch from that of a happy and sociable child to a sad, inactive and inexpressive adult;
    
  • risk of senile dementia (Alzheimer disease).
  
  

V. PROGNOSIS

• life expectancy, formerly poor, has greatly increased, due to antibiotherapy and surgery.
  
  
• prognosis can be impaired by:
  
  1 - the extreme susceptibility to infections.
  2 - malformations, cardiac malformations in particular.
  3 - acute leukemia (in 1 % of trisomy 21 infants/children, i.e. 20 times more frequently than in the general population).
  
  
  
• intellectual prognosis: (see evolution).

VI. TREATMENTS

• surgery in the case of malformation(s).
  
• antibiotherapy of infections; antifungal treatment of athletic foot.
  
• medical-paramedical-pedagogic cares; psychomotor therapy, kinesitherapy, orthophony.
  
• thyroid function repeated examinations (once a year).
  
• ophtalmologic tests (watch the hypersensitivity to atropine), auditive tests.
  
• cervical X-rays (cervical instability--> risk of cervical vertebrae dislocation).
  
• flat foot (special shoes, tricycle are recommended).
  
• flat dorsum (swimming recommended).
  
• keloid scars (surgery only when needed, avoid plastic surgery).
  
• artistic creativity should be developed and supported.

Contributor(s)

Written	08-2000	Jean-Loup Huret, Pierre-Marie Sinet
		CNRS UMR 8602, Faculté de Médecine Necker Enfants Malades, Paris, Franc

Citation

This paper should be referenced as such :

Huret JL, Sinet PM . Trisomy 21. Atlas Genet Cytogenet Oncol Haematol. August 2000 . URL : http://AtlasGeneticsOncology.org/Educ/PolyTri21Eng.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Apr 17 13:58:23 2008

For comments and suggestions or contributions, please contact us