Down syndrome is a genetic disorder caused by the presence of an extra chromosome 21. It is characterized by mild to moderate intellectual disability, distinctive facial features, and often physical growth delays. The majority (95%) of cases are trisomy 21, where each cell has 3 copies of chromosome 21. Management involves screening and diagnosis during pregnancy, monitoring for common comorbidities, and early intervention for optimal development.

1. Down Syndrome
Mugemana Henri Paterne
Supervised by Prof Dr Hoda Ghareeb

2. Introduction
Definition
● Down syndrome or trisomy 21, is a genetic
disorder caused by the presence of all or part of a
third copy of chromosome 21.2
○ Usually associated with
■ Physical growth delays,
■ Mild to moderate intellectual disability,
■ Characteristic facial features.1
1. Weijerman, ME; de Winter, JP (Dec 2010). "Clinical practice. The care of children with Down syndrome". European Journal of Pediatrics. 169 (12): 1445–52.
doi:10.1007/s00431-010-1253-0. PMC 2962780. PMID 20632187.
2. Patterson, D (Jul 2009). "Molecular genetic analysis of Down syndrome". Human Genetics. 126 (1): 195–214. doi:10.1007/s00439-009-0696-8. PMID 19526251. S2CID
10403507.
→ A female karyotype with trisomy 21

3. Introduction
Classification
3 types of Down syndrome: difference at the chromosomal level
● Trisomy 21: ~ 95% → each cell in the body has 3 separate copies of chromosome
21 instead of the usual 2 copies.
● Translocation Down syndrome: ~ 3% → an extra part or a whole extra chromosome
21 is present but attached or “trans-located” to a different chromosome rather than
being a separate chromosome 21.
● Mosaic Down syndrome: 2% → Mosaic means mixture or combination. For children
with mosaic Down syndrome, some of their cells have 3 copies of chromosome 21,
but other cells have the typical two copies of chromosome 21.

4. Introduction
Clinical Picture
Pavarino Bertelli Érika Cristina, Biselli Joice Matos, Bonfim Daiana, Goloni-Bertollo Eny Maria. Clinical profile of
children with down syndrome treated in a genetics outpatient service in the southeast of Brazil. Rev. Assoc. Med.
Bras. [Internet]. 2009 [cited 2020 Dec 27] ; 55( 5 ): 547-552. Available from: https://doi.org/10.1590/S0104-
42302009000500017.

5. Clinical picture
● Congenital Cardiac Defects (CHD)
○ The leading cause of morbidity and mortality, especially in the 1st 2 yrs of life.
○ The incidence: ~ 50 %
○ Types:
■ AVSD: 40 %
■ VSD: 32 %
■ Secundum Atrial defect: 10 %
■ ToF: 6 %
■ PDA: 4 %
Introduction
https://www.ncbi.nlm.nih.gov/books/NBK526016/

6. Introduction
Clinical picture
● Gastrointestinal (GI) abnormality
○ Structural defects can occur anywhere from the mouth to anus
→ Duodenal and small bowel atresia or stenosis
→ Annular pancreas,
→ Imperforate anus
→ Hirschsprung disease: 2% of Down Sd patients & 12% of hirschsprung have Down Sd
● Prone to many other GI disorders
→ Gastroesophageal reflux (GERD)
→ Chronic constipation,
→ Intermittent diarrhea
→ celiac disease: ~ 5% of these patients, recommended yearly screening
https://www.ncbi.nlm.nih.gov/books/NBK526016/

7. Introduction
Clinical picture
● Hematological abnormalities in a newborn with Down sd ( HANDS )
○ Neutrophilia: 80 % of Down sd babies
○ Thrombocytopenia: 60%
○ Polycythemia: 34%
○ Transient myeloproliferative disorder
→ About 10% of patients with Down sd.
→ If in the fetus, it can cause spontaneous abortion.
● 10 times more at risk of developing leukemia
→ 2% of all pediatric acute lymphoblastic leukemia and 10% of all pediatric acute
myeloid leukemia
https://www.ncbi.nlm.nih.gov/books/NBK526016/

8. Introduction
Clinical picture
● Neurologic disorders
○ Reduced brain volume especially hippocampus and cerebellum
■ Hypotonia is the hallmark of babies with Down syndrome and present in
almost all of them → responsible for delayed motor development
○ 5 - 13 % have seizures → 40% before their 1st birthday
○ High risk of early-onset of Alzheimer disease
■ 50% to 70% of patients developing dementia by the age of 60
https://www.ncbi.nlm.nih.gov/books/NBK526016/

9. Introduction
Clinical picture
● Endocrine disorders
○ Hypothyroidism can be congenital or acquired.
■ Hyperthyroidism much less frequent as compared to hypothyroidism, although
the incidence rate still exceeds that of the general pediatric population.
○ Abnormalities in sexual development
■ delayed puberty in both genders
○ Insulin-like growth factor responsible for the delay in skeletal maturation and short
stature.
https://www.ncbi.nlm.nih.gov/books/NBK526016/

10. Introduction
Clinical picture
● Musculoskeletal Disorders
○ Reduced muscle & retarded gross motor skills → hypotonia & ligamentous laxity
○ Vit D deficiency → inadequate exposure to sunlight, malabsorption secondary to celiac disease, increased breakdown
because of anticonvulsant therapy…
● Refractive Errors and Visual Abnormalities
○ blepharitis (2-7%), keratoconus (5-8%), cataract (25-85%), strabismus (23 - 44%), refractive errors (18-58%)...
○ An eye exam recommended during the 1st 6 months of life and then annually
● Otorhinolaryngological (ENT) Disorders
○ Hearing loss
https://www.ncbi.nlm.nih.gov/books/NBK526016/

11. Introduction
Magnitude:
→ Prevalence
→ Incidence
● Between 1 in 1,000 to
1 in 1,100 live births
worldwide
→ Mortality
● 25-30% die during the
first year of life.
● The median age at
death: mid-50s.
● In 2010: 17000
deaths

12. Descriptive
epidemiology
● Place
→ Globally
● Person & Time
○ Advancing maternal age: 35
yrs or older
○ Father's older age is also a
risk factor in those women but
not in younger than 35

13. Risk factors
● Maternal age
● Maternal exposure to x-rays
● Parents carrying down syndrome gene

14. Management
Diagnosis
➢ Diagnosis
→ Ultrasound between 14 and 24 weeks of gestation (increased nuchal fold thickness, small or no nasal bone and large
ventricles)
→ Amniocentesis and chorionic villus sampling ( a/w small risk of miscarriages: 0.5% to 1%)
→ Percutaneous umbilical blood sampling (PUBS): PCR based method

15. Management
● Prevention (1ry level):
○ Avoiding reproduction at advanced maternal age
○ Preimplantation genetic diagnosis for couples who are at high risk of Down's syndrome
○ Folic acid supplementation
→ There is a growing body of evidence suggesting that Down Sd might be linked to abnormal folate and methyl
metabolism.This can lead to DNA hypomethylation, instability, abnormal segregation and aneuploidy.
Cuckle HS. Primary prevention of Down's syndrome. Int J Med Sci. 2005;2(3):93-9. doi: 10.7150/ijms.2.93. Epub 2005 Jul 1.
PMID: 16007260; PMCID: PMC1168873.

16. Management
● Prevention (2ry level):
○ Postnatal
■ The American Academy of Pediatrics recommends screening individuals with Down
Syndrome for particular diseases
● Eye exam every year during infancy
● Hearing tests every 6 - 12 months, depending on age
● Dental exams every 6 months
● X-rays of the upper or cervical spine between ages 3 - 5 years
● Pap smears and pelvic exams beginning during puberty or by age 21
● Thyroid testing every 12 months
https://www.wikidoc.org/index.php/Down_syndrome_secondary_prevention

17. Management
● Prevention (2ry level):
○ Birth
■ Evaluation of the red reflex can help identify congenital cataracts.
■ Movement of the eyes observed to identify strabismus.
■ Constipation should raise concerns for Hirschsprung's disease
● Heart U/S should be done immediately in order to identify congenital heart disease
● A complete blood count to identify pre-existing leukemia
● A hearing test using brainstem auditory evoked responses (BAERS) testing should be performed
● The thyroid function tests.

18. Management
● Prevention (2ry level):
○ Childhood and adulthood
■ Special growth charts are available so that DS children can be compared with other children with DS.
■ Thyroid function testing should be performed at 6 months and 12 months of age as well as yearly
thereafter.
■ Evaluation of the ears for infection as well as objective hearing tests should be performed at every visit.
■ Formal evaluation for refractive errors requiring glasses should be performed at least every 2 years with
subjective vision assessments with each visit.
■ After the age of 3, an x-ray of the neck should be obtained to screen for atlanto-axial instability. As the
child ages, yearly symptom screening for obstructive sleep apnea should be performed.

19. Management
● Prevention (3ry level):
○ Cardiac referral regardless of the clinical signs of congenital heart disease which if
present should be corrected within the first 6 months of life to ensure optimum
growth and development of the child.
○ Other specialties involved include a developmental pediatrician, pediatric
pulmonologist, gastroenterologist, neurologist, neurosurgeon, orthopedic
specialist, child psychiatrist, physical and occupational therapist, speech and
language therapist, and audiologist.

20. References
● Weijerman, ME; de Winter, JP (Dec 2010). "Clinical practice. The care of children with Down syndrome".
European Journal of Pediatrics. 169 (12): 1445–52. doi:10.1007/s00431-010-1253-0. PMC 2962780. PMID
20632187.
● Patterson, D (Jul 2009). "Molecular genetic analysis of Down syndrome". Human Genetics. 126 (1): 195–
214. doi:10.1007/s00439-009-0696-8. PMID 19526251. S2CID 10403507.
● https://www.ncbi.nlm.nih.gov/books/NBK526016/
● Cuckle HS. Primary prevention of Down's syndrome. Int J Med Sci. 2005;2(3):93-9. doi: 10.7150/ijms.2.93.
Epub 2005 Jul 1. PMID: 16007260; PMCID: PMC1168873.
● https://www.wikidoc.org/index.php/Down_syndrome_secondary_prevention