Down syndrome is a genetic condition caused by trisomy of chromosome 21. It occurs in about 1 in 700 live births. Clinical features include intellectual disability, characteristic facial features such as a flat face, upward slanted eyes, and a protruding tongue. Individuals with Down syndrome also have an increased risk of certain medical conditions such as congenital heart defects and thyroid problems. Prenatal screening and diagnostic tests can identify Down syndrome in utero. Lifelong medical care is important to monitor development, screen for associated conditions, and support quality of life.
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Down syndrome
1. Down syndrome
Dr. Neha Sharma
DNB (Pediatrics) Resident, III rd Year
Santokba Durlabhji Memorial Hospital,
Jaipur
2. OUTLINE
GENETICS
CLINICAL FEATURES
PRENATAL DIAGNOSIS
AGE SPECIFIC HEALTHCARE GUIDELINES
RECURRENCE
COUNSELLING
3. Brief Historical Perspective
2.5k year old artefacts
depicting typical
features
First described by
John Langdon Down
in 1866
Discovered that cells
had an extra
4. Genetics
Trisomy 21 (47, +21), - 94 %
frequency maternal age
Robertsonian Translocation involving
chromosome 21- Approx. 3-4 %, not
related to maternal age.
Trisomy 21 Mosaicism – 2 to 3 %
cases
6. Chromosome 21
≥ 400 genes
2/3 of these are “compensated”
1/3 are over-expressed referred to as being
“dosage sensitive.”
May be “typical” or “amplified”
13. Maternal Age
(Years)
Incidence in term
live births
15-29 1 in 1500
30-34 1 in 800
35-39 1 in 270
40-44 1 in 100
> 45 1 in 50
Relation with maternal age
contd.
Ref: Smith’s Recognizable
patterns of Human malformations
7th edn.
15. Site of Translocation Percentage
Both parents normal <1%
Mother carrier 10%
Father carrier 2.5%
Either parent t(21q;21q) 100%
Mosaics <1%
16. Mosaicism
Non disjunction event early in
embryogenesis in a normal embryo
Down Syndrome embryo undergoes
division
some cells revert to normal
Considerable variability in proportion of
affected cells in tissues
17. Clinical features
Most Common pattern of
Human malformation
Most Common genetic cause
of severe Intellectual Disability
30. Intellectual Disability
From Levine MD, Carey WB, Crocker AC, editors: Developmental-behavioral
pediatrics, ed 2, Philadelphia, 1992, Saunders.
31. Clinical features in Adolescence
and Adult
Puberty
- in Girls menarche is only slightly
delayed. Fertility presumed
- in Boys are usually infertile due to low
testosterone levels
Increased risk of dementia (50-60% by
70)
Increased risk of Alzheimer’s
Shorter life expectancy (58.6 yrs)
32. Prenatal Diagnosis
PRENATAL SCREENING
-“Triple/Quad/Pentad screen" can be done
in
1st & 2nd trimesters (alone or sequentially or
in combination)
Alpha-fetoprotein
Unconjugated Estriol
Free β subunit of Human Chorionic
Gonadotropin (hCG)
Inhibin A
36. A New Maternal Blood Test?
January 2011, a research group from
China
Study in the British Medical Journal
High rate of correct diagnosis of
Trisomies
Using the mother's blood
Looks for “cell-free DNA” of foetal origin
could eliminate the need for 90% of
invasive diagnostic testing
Large scale trial ongoing
37. Counts sections of
DNA by high speed
sequencing
More than expected
foetal DNA denotes an
abnormality
PPV 45.2 cf 4.2 by
standard blood tests
(10 times more
sensitive)
Similar results for
Edwards Syndrome
Courtesy Illumina
38. Amniocentesis
15 – 18 wks GA
20 ml fluid
Ultrasound guided
Pregnancy loss 1 in 300
10 – 13 wks GA
Needle biopsy under
ultrasound guidance
Pregnancy loss 1 in 100
Chorionic Villus Sampling
43. Healthcare Guidelines (Age
Specific)
INFANCY (2-12 MONTHS)HISTORY
◦ Parental concerns
◦ Respiratory infections
(especially otitis media)
◦ Constipation (use
aggressive dietary
measures, consider
Hirschprung’s)
◦ Vision/Hearing
EXAM
◦ General
neurological, neuromotor, m
usculoskeletal exam
◦ TMs (refer to ENT if you
cannot see them and are
suspicious of otitis)
LAB, CONSULTS
◦ If not done as
newborn, pediatric cardiology
evaluation and ECHO ( VSD
or AV septal defect ,quiet
progressive pulmonary
hypertension)
◦ BERA or other assessment of
hearing by 6 months if not
done as newborn.
◦ Pediatric opthalmology
evaluation by 6-12 months if
not done as newborn.
◦ ENT for recurrent otitis.
◦ T4, TSH (if not done)
45. Self Help Skills
SKILL Down syndrome
Average (mo) Range(mo)
Normal Children
Average (mo) Range(mo)
EATING
Finger feeding 12 8 - 28 8 6 - 16
Using
spoon/fork
20 12 - 40 13 8 - 20
TOILET TRAINING
Bladder 48 20 - 95 32 18 - 60
Bowel 42 28 - 90 29 16 - 48
DRESSING
Undressing 40 29 - 72 32 22 - 42
Putting clothes
on
58 38 - 98 47 34 - 58
From Levine MD, Carey WB, Crocker AC, editors: Developmental-
behavioral pediatrics, ed 2, Philadelphia, 1992, Saunders.
46. Healthcare Guidelines (Age Specific)
INFANCY (2-12 MONTHS)
DEVELOPMENTAL
◦ Early Intervention
◦ Physiotherapy, Oral Therapy evaluations
◦ Developmental assessment
RECOMMENDATIONS
◦ Family support
◦ SBE prophylaxis as indicated
47. Healthcare Guidelines (Age Specific)
CHILDHOOD (1-12 YRS)
HISTORY
◦ Parental concerns
◦ Current level of functioning
◦ Current programming (3-4
year old program, school,
special education)
◦ Behavior problems
◦ Ear problems
◦ Sleep problems
◦ Constipation
◦ Obesity
◦ Review audiologic and thyroid
function tests
◦ Review opthalmologic and
dental care
EXAM
◦ General pediatric and
neurologic exam.
LABS, CONSULTS
◦ T4,TSH yearly
◦ ECHO if not done
◦ Auditory testing yearly (1-3
yrs),every 2 years (3-
13Years)
◦ Eye exams every 2 years if
normal, more often if
abnormal
◦ Lateral C-spine films (neutral,
flexion and extension) at 3
years and l2 years for
48.
49. Healthcare Guidelines (Age
Specific)
CHILDHOOD
DEVELOPMENTAL
◦ Enroll in appropriate educational program
◦ Consider augmentive communication device as indicated
RECOMMENDATIONS
◦ Twice daily tooth brushing
◦ Caloric intake below RDA
◦ Monitor diet, high fiber
◦ Exercise
◦ Oral Therapy, Physiotherapy as needed
◦ SBE prophylaxis as needed
◦ Monitor family needs for respite care, supportive
counselling, behavior management techniques
◦ Consider pneumovax and annual flu vaccines
◦ Reinforce the importance of good self-care skills
(grooming, dressing, money management skills)
50. Healthcare Guidelines (Age Specific)
ADOLESCENCE (12-18 YEARS)
HISTORY
◦ Interval medical history
◦ Sleep apnea
◦ Vision/Hearing
◦ Behavioral problems
◦ Address sexuality issues
EXAM
◦ General physical and
neurological exam (r/o
atlanto-axial dislocation
◦ Obesity
◦ Pelvic if sexually active
LAB, CONSULTS
◦ T4, TSH yearly
◦ Hearing and Vision every
other year
◦ ECHO for individuals
without CHD once in early
adulthood (18-20 years)
to rule out valvular
disease
◦ Consider gynecologist
experienced in working
with special needs
individuals for pelvic
exam for sexually active
teenager (r/o sexual
abuse)
51. Healthcare Guidelines (Age Specific)
ADOLESCENCE (12-18 YEARS)
RECOMMENDATIONS
◦ Begin transition planning
◦ Dental exams twice yearly
◦ SBE prophylaxis as needed
◦ Annual flu shot
◦ Diet and exercise program
◦ Update estate planning and custody arrangements
◦ Social/recreational programs
◦ Discuss plans for alternative long term living arrangements if
eligible
◦ Reinforce good self-care skills
◦ Vocational issues
◦ Smoking, drug, alcohol education
◦ Health and sex education including counselling regarding
abuse prevention
52. Healthcare Guidelines (Age Specific)
ADULT (>18 YEARS)
HISTORY
◦ Interval medical history
◦ Sleep apnea
◦ Thyroid
◦ Monitor for loss of skills,
behavioral changes, mental
health problems, dementia
(decline in function memory
loss, ataxia, seizures)
◦ Incontinence of urine and/or
stool
◦ GERD
◦ Atlanto-axial instability
◦ Obesity
EXAM
◦ General physical and
neurologic exams
◦ Monitor weight
◦ Pap smears for sexually
active women every 1-3 years
◦ Pelvic every 3 years for non-
sexually active women
◦ Yearly breast exams
◦ Testicular exam for men
◦ Prostate exam for men
53. Healthcare Guidelines (Age Specific)
ADULT (>18 YEARS)
LAB, CONSULTS
◦ T4, TSH yearly
◦ Eye exam every 2 years
◦ Auditory testing every 2 years
◦ Repeat C-spine films once in adulthood
◦ ECHO to rule out valvular disease once in early
adulthood
◦ Mammograms yearly from age 50 years
◦ Mammograms yearly from age 40 years for women
with first degree relative with breast cancer
◦ Twice yearly dental exams
◦ Mental health referral ?
54. Healthcare Guidelines (Age Specific)
ADULT (>18 YEARS)
RECOMMENDATIONS
◦ Consider augmentive communication device
◦ Vocational issues
◦ Discuss plans for alternative long term living arrangements
◦ Discuss advanced directives. Update estate planning
◦ Guardianship issues
◦ Social/recreational programs
◦ Reinforce self-help skills
◦ Bereavement counselling when indicated
◦ SBE prophylaxis for patients with cardiac disease
◦ Annual flu shot
◦ Diet and exercise programs
55. Healthcare Guidelines (Age Specific)
ADULT (>18 YEARS)
PSYCHIATRIC DISORDERS
◦ r/o medical causes for changes in behavior, loss of skills,
incontinence, change in appetite, weight, sleep or energy
level, aggressive behavior, crying.
◦ Consider pain from GERD, dental abscess, sinusitis, otitis,
fracture, glaucoma
◦ Thyroid
◦ Sleep apnea
◦ Polypharmacy
◦ Depression
◦ Psychosis and schizophrenia uncommon
◦ OCD
◦ Anxiety disorders
◦ Dementia (Alzheimer)
56. Mortality
Median age of death increased from 25
yrs in 1983, to 58.6 years currently
Most likely cause of death: CHD,
Dementia, Hypothyroidism and Leukemia.
Improved survival due to increased
placements of infants in homes and
changes in treatment for common causes
of death
Survival is better for males and Blacks
57. Risk of recurrence
Increased by 1% above baseline risk for
maternal age.
Detection of translocation is an indication
for genetic analysis of parents
◦ Both parents normal : 2 – 3 %
◦ Mother a carrier : 2 %
◦ Chromosome 14 translocation
Increased risk of other trisomies in future
pregnancy
58. Counselling
Genetic information
◦ Caused by extra chromosome 21 material
◦ Diagnosis confirmed by chromosome analysis
◦ Recurrence risk for future pregnancies
Physical features
◦ Hypotonia
59. Counselling
Associated medical complications
◦ Heart defect possibly requiring open heart
surgery
Intellectual disability and developmental
delay
◦ Mild-to-moderate intellectual disability
◦ Developmental delay in achieving milestones
◦ Need for physical, occupational, and speech
60. Counselling
Long-term prognosis
◦ Inclusion in regular classes
◦ Special education classes
◦ Participate in community sports, activities
◦ Have friends
◦ More like other children than different
61. Counselling
Informational resources and referrals
◦ Local support groups
◦ Advocacy organizations and websites
◦ Early intervention centers
◦ Printed or written material
◦ Fact sheets or brochures
◦ Books
◦ Contact with families raising a child with
DS
trained at the London Hospital, was the first to recognize what he called “Mongolian idiocy” as a syndrome when publishing a paper on mental retardation , called it a “throwback” to a “lower” race, “children appeared similar, like brothers and sisters”,disorder became known as “Mongolism.”
Translocation with other acrocentricchromosomes 13,14,15, 22. Supernumary chromosome maternal in 90% .
compensated meaning that the amount of their product is similar to that seen in a typical populationMost of these are expressed at 1.5 x the typical amount (as expected).Some of these actually have amplified expression (more than 1.5 x the typical amount).
Smith’s, Nelson’s, overall incidence 1 in 660 liveborn
In AML, acute megakaryocytic leukemia is the most common subtype.
25% live upto 63yrs
Interpretation depends on the correct gestational age estimation, most appropriately done by USG, during the 1st trimester using fetal nuchal translucency (NT) thickness that can be done alone( <= 70% sensitive) or in conjunction with maternal serum β-hCG and pregnancy-associated plasma protein-A (PAPP-A) ( 87% sensitive) 1st 2nd trimester screen with NT and BPP ( Integrated screen) 95% detection rates
Nuchal translucency and nuchal fold, correlated with the CR length, done in 11 – 14 weeks
false positive rates of detection 0.5 % cf 4.2 % for trisomy 13 n 18 combined screening tests
Depression: sad, irritable mood, disturbances in appetite, sleep, energy, loss of interest in previously enjoyable activities, skill and memory loss, self-talk, withdrawal. Depression may be seen in reaction to loss: death in the family, loss of caretaker, roommate.
fewer than expected deaths by solid tumors and ischemic heart disease, increased risk of adult deaths due to congenital heart disease, seizures, and leukemia. leukemias accounted for 60% of all cancers in people with Down and 97% of all cancers in children with Down syndrome. decreased risk of solid tumors in all age groups, including neuroblastomas and nephroblastomas and epithelial tumors in adults with Down syndrome.
If one parent carries a balanced translocation, the recurrence risk depends on the sex of the carrier parent and the specificchromosomes that are fused.4
