Downs, Edwards, Patau, Klinefelter, Turner, and other relevant Syndromes explained. The file includes their various mechanisms and clinical features. Together with their recommended management.

1. TRISOMY 21 AND OTHER
CHROMOSOMAL
ABNORMALITIES
PRESENTERS: DAUDI CHIRANZI

2. OUTLINE
• Definitions
• Classification
• Mechanism of abnormalities
• Epidemiology
• Etiology
• Pathogenesis
• Clinical features
• Diagnostic evaluation
• Treatment

3. DEFINITIONS
• Chromosome abnormality:- Missing, extra, or irregular portion of
chromosomal DNA.
• Aneuploidy:- Abnormal number of chromosomes that are not an exact
multiple of a haploid number.
• Haploid:- Number of chromosomes in ova and sperms i.e. half the
number in normal somatic cells.-23 in normal human beings.
• Euploid:- A cell whose chromosomes are an exact multiple of 23 (46, 69,
92).
• Diploid:- State of cell containing 2 haploid sets derived from the father
and mother.

4. • Polyploid/heteroploid:- Are euploid cells with more than the normal
diploid number of 46 (2n) chromosomes
• Trisomy:- Presence of a single extra chromosome, yielding a total of
three chromosomes instead of a pair. Can be:-
• Full trisomy:- An entire extra chromosome is copied.
• Partial trisomy:- An extra copy of a part of a chromosome.
• Monosomy:-The presence of only one chromosome from a pair.
Partial where only a portion of the 2nd chromosome is present
• Mosaicism:- Describes an individual with two or more different cell
lines derived from a single zygote. Usually the result of mitotic
nondisjunction.

5. CHROMOSOMAL ABNORMALITIES
a) Chromosomal abnormalities may be classified based on which
chromosome is affected:-
• Autosomal abnormalities
1. Downs Syndrome (Trisomy 21)
2. Edwards Syndrome (Trisomy 18)
3. Patau Syndrome (Trisomy 13)
• Sex chromosome abnormalities
1. Turner syndrome (45-X)
2. Klinefelter’s syndrome (47-XXY)

6. b) Classification based on number or structure and content of the
chromosome:-
• Numerical defects/genome mutations- Abnormalities of the euploid
number of chromosomes (46) e.g. trisomy 21, trisomy 18, trisomy 13,
Klinefelter syndrome, and Turner syndrome.
• Structural defects/chromosomal mutations- From chromosome
breakage and rearrangements, e.g. balanced or unbalanced
translocation, deletion, duplication, inversion, e.g. Wilms tumor with
aniridia (11q deletion), Prader-Willi syndrome

7. MECHANISMS OF CHROMOSOMAL
ABNORMALITIES
1. Deletion- Portions of the chromosome are lost
2. Duplication- Genetic material present twice
3. Inversion- A segment of chromosome is reversed end to end (180
degrees)
4. Insertion- Genetic material is added from another chromosome
5. Translocation- Material is swapped with another chromosome
6. Non-disjunction- Failure of chromosomes to separate during
meiosis, e.g. DS, ES, PS, TS, KS, etc.

8. DOWNS SYNDROME (TRISOMY 21)
• Caused by the presence of all or part of a third copy of chromosome
21, due to nondisjunction.
• Commonest & best known chromosomal disorder in humans.
• Most common cause of intellectual disability.
• Characterized by mental retardation, dysmorphic features, congenital
malformations and other distinctive phenotypic traits.
• Associated with multiple systemic complications.

10. Epidemiology
• First-trimester prevalence of approximately 1 in 340
• 1 in 800 births globally.
• Incidence of changes at various maternal ages.
• 15-29 1:1500 live births
• 30-34 1:800 live births
• 35-39 1:270 live births
• 40-44 1:100 live births
• >45 1:50 live births
• Male:Female 1.15:1
• Life expectancy –approximately 50 yrs
• Kenya: estimates 40,000 living with it.
• The rate in Kenya, as that of global front, is increasing at 1:800.

11. Risk Factors for DS
• Advanced maternal age(>35yrs)
• Previous child with Down’s syndrome
• Family history
• A chromosomal translocation, inversion, or aneuploidy, or a partner
with one of these abnormalities
• Carriers of the genetic translocation for Down syndrome

12. Etiology
• 3 cytogenic variants
• Trisomy 21 (94% of patients)
• Chromosomal translocation (3.4% of patients) mainly the Robertsonian
translocation at chromosome 21
• Mosaicism (2.4% of patients)
• Approx. 75% of the unbalanced translocations are de novo & approx. 25%
from familial translocation.
• A free trisomy 21 results from nondisjunction during meiosis in which two
homologous chromosomes fail to separate during anaphase.
• Most common error (95%) is maternal nondisjunction in the 1st meiotic
division. Mitotic errors also occur (5%)
• The remaining errors are paternal in origin & meiosis II errors predominate.

13. Pathogenesis
1. Trisomy 21 (95%)
• Over expression of genes in q21.1-22.2 is sufficient to cause Down
syndrome, due to nondisjunction.
• The DSCR contains genes that code for enzymes e.g.
• Superoxide dismutase 1(SOD1)
• Cystathionine beta-synthase (CBS)
• Glycinamide ribonucleotide synthase-aminoimidazole
ribonucleotide synthase- glycinamide formyl transferase
(GARS-AIRS-GART)

14. 2. Robertsonian Translocation (3-4%)
• When genetic material from chromosome 21 becomes attached to
another chromosome, causing 46 chromosomes with 1 having extra
material from chromosome 13, 14, and 22 attached.
• De novo or transmitted by one of the parents.
• Translocations are of the centric fusion type.
They frequently involve
• Chromosome 14 (14/21 translocation)- Most common
• Chromosome 22 (22/21 translocation)
• 46 chromosomes, but one chromosome 21 contains the long arms of
both chromosomes 14 and 22.
• Not related to maternal age

15. 3. Mosaicism
• A postzygotic event (i.e. after fertilization).
• Most cases result from a trisomic zygote with mitotic loss of one
chromosome, hence 2 cell lines found:
• One with a free trisomy
• One with a normal karyotype
• This leads to great phenotypic variability ranging from near normal
to the classic trisomy 21 phenotype.

16. PATHOPHYSIOLOGY
• The extra chromosome 21 affects almost every organ system & results
in a wide spectrum of phenotypic consequences:-
• Decreases prenatal viability
• Increases prenatal & postnatal morbidity.
• Delayed physical growth, maturation, bone development, dental
eruption.
• Developmental abnormalities result from loss of chromosomal balance

17. Hypotheses:
• Developmental disability
Loss of chromosomal balance
• Gene dosage effect
Genes on chromosome 21 are overexpressed in cells & tissues
The extra copy of the proximal part of 21q22.3 appears to result in
the typical phenotype, which includes:
Mental retardation
Characteristic facial features
Hand anomalies
Congenital heart defects– approx. 50% (VSD & AVD), which is
characterized by complications such as bronchopneumonia.

18. • The 21q22.1- q22.3 region (DSCR) appears to contain the
genes responsible for the congenital heart disease in down
syndrome.
• A new gene DSCR1 in region 21q22.1-q22.2 is highly
expressed in the brain & the heart leading to mental retardation
and cardiac defects.

19. EDWARDS SYNDROME (TRISOMY 18)
• Incidence 1/8000
• Severe Mental retardation and many birth defects
• >90% dead in 1st year.
• Life expectancy: Only 5% live >1year
• General characteristics
• Premature births
• Polyhydramnios
• Developmental delays
• Pre & postnatal growth retardation
• Low birth weight

20. Edwards Syndrome
• Maternal advanced age is directly proportional to probability
for this disorder.
• Second most common autosomal trisomy after trisomy 21.
• Affects all organ systems.
• There is a 3:1 female-to-male ratio among affected infants.
• Three aetiologies:-
Trisomy 18- meiotic nondisjunction.
Translocation involving chromosome 18.
Trisomy 18 mosaicism

21. Clinical Features
• History
Intrauterine growth restriction
(IUGR)
Polyhydramnios
LBW
Premature births
• Head and Neck
Small and premature appearance
Tight palpebral fissures
Narrow nose and hypoplastic
Narrow bifrontal diameter
Prominent occiput
Pointy ears
low-set ears
Micrognathia
Cleft lip or palate
Small mouth
Microcephaly
• Chest
Short sternum,
Small nipples
Congenital heart disease
• VSD, ASD, PDA

22. • Hypogonadism
• Extremities
• Clinodactyly (incurving of 5th finger)
• Overlapping fingers (index over 3rd, 5th over 4th, closed fist) or
fixed finger contractures
• Rocker-bottom feet
• Limited hip abduction
• Hypoplastic nails
• Others
Hypertonia
Horseshoe kidney

23. Clinical Features

25. Complications
• Congenital heart disease occurs in greater than 50%:
Ventricular septal defects
Patent Ductus Arteriosus
• Gastrointestinal system is involved in approximately 75%:
Meckel diverticulum and
Malrotation are the predominant abnormalities
Omphalocele (Prenatally)

26. PATAU SYNDROME (TRISOMY 13)
• The least common and the most severe of the viable autosomal
trisomies.
• Life expectancy
• Only 5% live >6 months
• General
• Developmental delays
• Pre & postnatal retardation
• Renal abnormalies
• Nuclear projections in neutrophils

27. Aetiology
• Three etiologies:-
Trisomy 13- Meiotic nondisjunction
Unbalanced Robertsonian translocation, although balanced
Robertsonian translocation is also common.
Trisomy 13 mosaicism

28. Clinical features
• History
IUGR
Postnatal retardation
• Multiple congenital abnormalities.
• Classic triad:-
Micro/anophthalmia (“Without eye”)
Cleft lip and/or palate
Postaxial polydactyl

29. Clinical Features
• CNS
Holoprosencephaly with
incomplete development of
forebrain, olfactory and optic
nerves,
severe intellectual disability,
deafness
• Head and Neck
Abnormal auricles
Microphthalmia/anophthalmia
Colobomata
Sloping forehead
• Skin and limbs
Capillary hemangiomata,
• Extremeties
Clinodactyly
Polydactyly
Syndactyly
Hypoplastic/hyperconvex nails
Simian creases
• Chest (80%)-
VSD, PDA, ASD, and
dextroposition

30. • Abdomen
Omphalocele,
Incomplete rotation of colon,
Meckel diverticulum
• Renal
Polycystic kidney,
Hydronephrosis,
Horseshoe kidney
• Genitalia
Cryptorchidism in males
Bicornuate uterus in females

32. TURNER SYNDROME (45, X)
• A condition characterized by the complete or partial absence of the
second sex chromosome.
• 50% have a 45, X chromosome complement.
• 50% exhibits mosaicism and varied structural abnormalities of the X
or Y chromosome.
• In 75%, the lost chromosome is of paternal origin.
• Incidence-1 in 5,000 female live births.
• 95–99% of 45,X conceptions are miscarried.

33. Clinical Features
History
• Maternal age is not a predisposing factor for children with 45, X.
• 45,X is mostly associated with spontaneous abortion. It has been
estimated that 95-99% of 45,X conceptions are miscarried.
• Some newborns may be phenotypically normal.
• Prenatal testing: FISH is a technique that can be used for rapid
diagnosis in the prenatal detection of common fetal aneuploidies
including chromosomes 13, 18, and 21 as well as sex chromosomes.

34. Head to toe
• Small for Gestational Age
• Redundant nuchal skin (in utero
cystic hygroma)-webbed neck
• Protruding ears
• Congenital lymphedema
• Patella dislocation
• Widespread nipples
• Shield chest
• Low posterior hairline
• Increased carrying angle of elbow
(cubitus valgus)
• Madelung deformity
(chondrodysplasia of distal radial
epiphysis)
• Congenital hip dislocation
• Coarctation of aorta
• Bicuspid aortic valve
• Cardiac conduction
abnormalities
• Horseshoe kidney

35. • Hypoplastic left heart syndrome
• Gonadal dysgenesis (infertility,
primary amenorrhea)
• Gonadoblastoma (if Y
chromosome material present)
• Learning disabilities (nonverbal
perceptual motor and visuospatial
skills) [in 70%]
• Developmental delay (in 10%)
• Short stature and scoliosis
• Social awkwardness
• Hypothyroidism (acquired in 15-
30%)
• Type 2 diabetes mellitus (insulin
resistance)
• Strabismus
• Red-green colorblindness (as in
males)
• Cataracts
• Recurrent otitis media
• Sensorineural hearing loss
• Inflammatory bowel disease

37. KLINEFELTER SYNDROME
• It refers to a group of chromosomal disorders in which the normal
male karyotype (46,XY) has at least one extra X chromosome
• Incidence- 1 in 500 live born males
• Most common cause of hypogonadism and infertility in males
• 80%- have a male karyotype with one extra chromosome X—47,XXY
• 20%-have a higher grade of sex chromosome aneuploidy (48,XXXY;
48,XXYY; 49,XXXXY), mosaicism (46,XY/47,XXY), or structurally
abnormal X chromosomes.
• The greater the aneuploidy, the more severe the sexual and mental
impairment and dysmorphism.

38. Clinical Features
Presentation
• Many patients are phenotypically normal until after puberty
• Puberty occurs at normal age but testis are small
• Late development of secondary sexual characteristics
• Gynaecomastia
• Reduced intellect
• Language deficits and social domain
• Deficits in executive functions
• Infertility – aids in clinical diagnosis

40. OTHER SEX CHROMOSOME
ABNORMALITIES
1. Triple X Syndrome (XXX)
• A sex chromosome abnormality in which there are three X
chromosomes, resulting in a phenotypic female.
• About 1/1000 apparently normal females have 47XXX.
• Other physical abnormalities are rare.
• Sterility and menstrual irregularity sometimes occur.
• Mildly impaired intellect with IQ scores averaging just below 90 and
associated school problems occur when compared with siblings.

41. 2. The 47, XYY Syndrome
• A sex chromosome abnormality in which there are two Y
chromosomes and one X, resulting in a phenotypic male.
• Affected persons tend to be taller than average with a 10 to 15 point
reduction in IQ for their family.
• There are few physical problems.
• Minor behavior disorders, hyperactivity, attention deficit disorder, and
learning disabilities are increased.

42. OTHER AUTOSOMAL CHROMOSOME
ABNORMALITIES
1. Trisomy 8
• The Warkany Syndrome, which
usually characterised by:-
Mental retardation,
Specific facies,
Absent/dysplastic patellas
Joint contractures
Plantar/palmar furrows
Distinctively abnormal toe
posture
Vertebral anomalies,
Narrow pelvis,
Ureteral-renal anomalies
• Usually lethal
• Mainly caused by mosaicism

43. 2. Trisomy 9
• Almost always lethal.
• Presentation:-
Micrognathia
Bulbous nose
Low-set ears
Cleft palate
Skeletal abnormalities (e.g.
dislocated joins),
Heart abnormalities (e.g.
ventricular septal defect)
Hypoplastic genitalia
Renal abnormalities
Brain abnormalities
• Survival time after birth varies
between minutes to 9 months.
• Cause- Mosaicism

44. CHROMOSOMAL ANORMALITIES DUE
TO STRUCTURAL DEFECTS
Deletions
• Due to breakage, portions of the chromosome are lost (genetic
material is missing)
• Cri du chat syndrome- Chromosome 5
• Di George syndrome- Chromosome 22

46. Inversion

47. Duplication
• Genetic material is present twice, i.e. when a gene sequence is
repeated.

48. DIAGNOSIS
• Karyotyping
• FISH technique

49. CLINICAL MANIFESTATIONS AND MANAGEMENT
(TRISOMY 21)
MARITA NARESH

50. History
• Maternal risk factors:-
Advanced Age
Previous child with DS
Family history
Carriers of the genetic translocation for DS
Prenatal diagnosis of DS
Initial difficulty in establishing successful breastfeeding
Delay in cognitive abilities, motor developmental, language
development.
Parental concern about hearing, vision, developmental delay,
respiratory infections and other problems

51. CLINICAL FEATURES
DYSMORPHIC FEATURES
• Up slanting palpebral fissures, epicanthic folds, and brachycephaly are
nearly universal features of DS.
• Features predominantly affect the head and neck and the extremities.

52. Skull
• Brachycephaly
• Microcephaly
• Sloping forehead
• Flat occiput
• Large fontanels with late closure
• Absent frontal & sphenoid sinuses
• Hypoplasia of maxillary sinuses

53. Eyes
• Up-slanting palpebral
fissures
• Epicanthal folds
• Brushfield’s spots
• Refractive errors (50%)
• Strabismus (44%)
• Nystagmus (20%)
• Retinal detachment
• Tearing from stenotic
nasolacrimal ducts
• Congenital cataracts
(3%)
• Acquired cataract (30-
60%)
• Keratoconus in adults

54. Nose
• Flat face with increased interocular distance (hypertelorism)
• Hypoplastic nasal bone
• Flat nasal bridge
Ears
• Small with overfolded helix
• Chronic otitis media
• Hearing loss (38-78%)

56. Mouth & teeth
• (Relatively) small
mouth with tendency
to protrude tongue
• Fissured & furrowed
tongue
• Mouth breathing with
drooling
• Partial anodontia
(50%)
• Cleft lip or palate
• Malformed teeth
• Delayed tooth eruption
• Hypoplastic &
hypocalcified teeth
• Malocclusion
• Increased periodontal
destruction

57. Extremities
Short broad hands
Incurved fifth finger with hypoplastic middle phalanx
Transverse palmar crease
Space between the first and second toes (sandal gap)
Hyper flexibility of joints

59. Neonatal features
• Flat facial profile
• Slanted palpebral fissures
• Anomalous ears
• Hypotonia
• Poor Moro reflex
• Dysplasia of middle phalanx of fifth finger
• Transverse palmar (Simian) crease
• Excessive skin at back of the neck
• Hyper flexibility of joints
• Dysplasia of pelvis

60. Congenital heart defects
• Are common (40-50%) & observed in those who are hospitalized (62%) &
are a common cause of death in the first 2yrs.
Include:
• Complete atrioventricular septal defect (CAVSD) – 37%
• Ventricular septal defect (VSD) – 31%
• ASD – 15%
• Partial atrioventricular septal defect (PAVSD) – 6%
• Tetralogy of Fallot (TOF) – 5%
• PDA – 4%
• Miscellaneous – 2%

61. GIT abnormalities
• Occur in approx. 5%
• Duodenal atresia or stenosis
• Hirschsprung d’se
• Tracheoesophageal fistula
• Meckel diverticulum
• Imperforate anus
• Omphalocele
• Annular pancreas
• Increased incidence of celiac d’se

62. Endocrine abnormalities
• Thyroid; hypothyroidism, hyperthyroidism
• Congenital hypothyroidism, primary hypothyroidism, autoimmune
thyroiditis
• DM type 1
• 3 times common in DS

63. Hematologic disorders
• 65% of newborns with DS have polycythemia .
• Leucopenia, thrombocytosis is common in infancy.
• Transient myeloproliferative disorder TL/ TAM
• Almost exclusively affects newborns with DS
• Usually asymptomatic, with spontaneous resolution after 2-3 months
• Acute megakaryoblastic leukemia- most common
• Incidence 500 times greater in DS than without
• Up to 26 percent of infants with transient leukemia
• Acute lymphoblastic leukemia - 10 to 20 times higher in DS

64. Respiratory
• Sleep apnea — Obstructive sleep apnea (OSA) 30 to 75 percent of
children with DS.
• The mechanism includes soft tissue and skeletal alterations that lead to
upper airway obstruction.
• OSA in DS associated with dysphagia, gastrointestinal conditions such
as gastroesophageal reflux disease, and congenital heart disease

65. Neurological findings
• INTELLECTUAL DISABILITY; Almost all individuals with DS
have cognitive impairment.
• Most are mildly to moderately intellectually disabled, with an IQ of 50
to 70 or 35 to 50
• Developmental impairment becomes apparent in the first year of life.
Generally,
• Sitting (11 months),
• Creeping (17 months), and
• Walking (26 months) is twice the typical age

66. • Muscle hypotonia in newborns with decreased response to normal
stimuli; this improves with age.
• Articulatory problems
• Seizure disorders in 5-10% of pts.
Infantile spasms are the most common seizures observed in infancy
Tonic –clonic seizures are most common in older pts
• Early-onset Alzheimer’s and dementia

67. Behavioral and psychiatric disorders
• Psychiatric disorders affects 17.6% of individuals with DS <20 years
• Psychiatric disorders; major depressive illness or aggressive behavior
• Disruptive behavioral disorders; attention-deficit hyperactivity
disorder, conduct/oppositional disorder, aggressive behavior, OCD
• Autism is a common comorbidity of DS, affecting as many as 7%

68. Skin
• Palmoplantar hyperkeratosis
• Seborrheic dermatitis
• Fissured tongue
• Cutis marmorata
• Geographic tongue
• Xerosis
• Alopecia areata
• Growth; Short stature & obesity during adolescence

69. GUT
• Renal malformations
• Hypogenitalism (micropenis or small scrotum & testis)
• Hypospadias
• Cryptorchidism
• Delayed puberty
• Testicular cancer
REPRODUCTION
• Females with DS are fertile and may become pregnant.
• 50% risk of having child with DS
• Nearly all males with DS are infertile.
• Mechanism is impairment of spermatogenesis

70. ATLANTOAXIAL INSTABILITY
• Excessive mobility of the articulation of the atlas (C1) and the axis
(C2)
• May lead to subluxation of the cervical spine
• 13% of patients with DS have asymptomatic AAI
• Spinal cord compression due to the disorder affects approximately 2%
• SCC; neck pain, gait abnormalities, loss of bowel or bladder control,
signs of quadriparesis or quadriplegia
• Neck; Typically broad & short with excess skin on the back

71. IMMUNODEFICIENCY
• DS is associated with a variety of immunologic impairments that are
thought to be related to :
• Increased susceptibility to infection
• Autoimmune disorders
• Malignancies
• Chemotactic defects , decreased immunoglobulin levels , and
quantitative and qualitative abnormalities of the T cell and B cell

72. DIAGNOSIS
Prenatal
• Screening tests
• 1st trimester-triple /combination test
• Maternal serum beta human chorionic gonadotropin (beta-hCG)
• Maternal serum pregnancy-associated plasma protein-A (PAPP-A)
• Ultrasound measurement of nuchal translucency (NT)
• 2nd trimester-quadruple test
• Alpha-fetoprotein (AFP)
• Unconjugated estriol (uE3)
• Human chorionic gonadotropin (hCG)
• Inhibin A in maternal serum

73. Diagnostic Tests
• Amniocentesis 12-20 wks gestation.
• Chorionic Villus Sampling (CVS) 8 and 12 weeks.
• Percutaneous Umbilical Blood Sampling (PUBS) after 20 weeks.
Goal –Karyotyping
POSTNATAL
• Clinical diagnosis
• Physical features
• Tests for associated anomalies
• Confirmatory diagnosis -- Karyotyping

74. DIAGNOSIS OF ASS ANOMALIES
CVS
• ECHO for CHD
Hearing
• Auditory brainstem response (ABR),brainstem auditory evoked response
(BAER)
• Evaluate for O.M
Ophthalmic examination -Annual
• Strabismus, cataracts
CBC
• At birth to evaluate for myeloproliferative d/o and polycythenmia

75. THYROID
• TFT done at newborn period, repeat at 6,12 months ,then annually.
• DM
• Screen for DM
ATLANTOAXIAL INSTABILITY
• X-rays for AAI or subluxation at 3yrs of age.
• Evaluation for s/s of spinal injury
• Symptomatic children should have an MRI to clarify the extent of
spinal cord compression

76. TREATMENT
Treatment of associated complications to improve the quality of life

77. Treatment of assoc. complications
• Growth
• Growth monitoring(Growth chart for children with DS)
• Calcium, vitamin D supplements(to minimize bone loss)
• Prevent obesity; low caloric diet, physical activity
• Cardiac ; AVSD,ASD,VSD ,mitral prolapse repair
• Thyroid; Thyroxine
• Hearing; Rx otitis media, Hearing aids
• Sleep apnea; Correction of soft tissue and skeletal alterations
• Atlantoaxial instability; Orthopedic appliances, surgery

78. • Prompt surgical repair is necessary for GI anomalies
• Ophthalmologic
• Correction of strabismus, refractory errors
• Cataract surgery
• Periodontal disease/Dental caries
• Oral hygiene, fluoride treatments, good dietary habits
• Orthodontics
• Speech
• Dental corrections
• Speech therapy esp expressive language
• Family and parental distress; Counselling, psychotherapy

79. • Bacterial endocarditis prophylaxis in adolescents with cardiac disease.
• Patients with symptoms of arrythmias, episodes of fainting, abnormal
findings on ECG and palpitations or chest pain should refrain from
participating in sports and strenuous exercise.

81. Prognosis
• Overall outlook for individuals with DS has dramatically improved.
• Life expectancy improved from 25 years in 1983 to 60 yrs or higher
today.
• ≈ 75% of concepti with trisomy 21 die in embryonic or fetal life.
• ≈ 25-30% of DS die during the 1styr; CHD and respiratory infections
(bronchopneumonia).
• CHD is the major cause of early mortality in patients with DS.
• Mortality in the elderly ;dementia, mobility restrictions, visual
impairment, and epilepsy (but not cardiovascular disease)

82. THE END
‘‘ They are human, just like you and me.
They have feelings, fears, hopes, and dreams. They desire and deserve
patience, love, and community just as much as any other person in
the world. They have impact and when we reject them from our lives,
we are left misguided and incomplete’’.

83. THANK YOU!