Down syndrome, caused by an extra chromosome 21, is the most common chromosomal abnormality with an estimated incidence of 0.1% in live births, leading to various health issues and intellectual disabilities. The condition can manifest in three forms: standard trisomy 21, translocations, and mosaicism, with management necessitating a multidisciplinary approach including genetic counseling, early screening, and targeted therapies. Clinical features range from physical abnormalities and vision issues to higher risks of neurological disorders, emphasizing the importance of early intervention and tailored educational strategies.

1. By –
Anumeha Sharma
MPT (Neurology)

2. Introduction
 Named after a physician, “John Langdon
Down” in 18th century.
 Down syndrome is the most common
chromosomal abnormality. The estimated
global incidence of this of this
chromosopathy is around 0.1% in live birth.
 In 1959 a French doctor, named “Jerome
Lejeune” , discovered it was caused by the
inheritance of an extra chromosome 21.

3.  It is an chromosomal disorder caused by an
error in cell division resulting in the presence
of an additional third chromosome 21 or 21
trisomy.
 A ‘syndrome’ means a group of recognisable
characteristics occurring together. A
‘congenital’ syndrome is one present at birth.
 Down syndrome is one of the most leading
causes of intellectual disability and various
health issues.

5. Standard trisomy 21
 In this type of aberration, the carrier has 47
chromosomes, including three chromosomes 21.
 It accounts for nearly 90% to 95% of DS cases.
 The majority of free trisomy 21 cases (85-90%)
originates from errors in maternal meiosis.
 In particular, maternal meiosis I is the most
frequently affected stage of nondisjunction
(>75%), whereas maternal meiosis II errors
account for >20%.
 In 5% of free trisomy 21, paternal meiotic errors
can be observed, here meiosis II nondisjunction is
more frequent than meiosis I errors.

6. Nondisjunction is the failureof homologous chromosomes or sister
chromatids to separate properlyduring cell division.

8. Translocations
 Translocation occurs before fertilisation
where a part of an extra copy of chromosome
21 breaks off during cell division and
becomes translocated (attached) to another
chromosome in the egg or sperm cell.
 Affected individuals have two normal copies
of chromosome 21, in addition to an extra
attached chromosome 21.

9.  DS due to translocation is the only variant
that occurs independent of maternal age and
may be inherited from either parent.
 Approximately 4% of people with DS have
translocation,which may either be reciprocal
or Robertsonian.
 Reciprocal translocations are the most
common type and involve an exchange of
chromosome between any of the different
types, for example, between chromosome 1
and chromosome 9.

10.  Robertsonian translocations only involve
exchanges among chromosome numbers 13,
14, 15, 21 and 22.

12. Mosaic variant
 The mosaic variant is the least common
pattern of transmission of DS, occurring in 1%
– 2% of people with DS, and the error in cell
division occurs after fertilisation.
 Affected individuals have some cells with an
extra chromosome 21 and others with the
normal number, and this results in some body
cells containing 47 chromosomes and others
having the usual 46 chromosomes.

13.  The greater the number of normal cells in DS,
the higher the chances of higher cognitive
functions, with a possibility of less intellectual
impairment.

16. Risk Factors
 Advancing maternal age – usually women of
age 35 or above.
 Mothers who already have child affected with
down syndrome.
 Being carriers of the genetic translocation for
Down syndrome.

18. Habitual risk factor
 Maternal cigarette smoking
 Use of oral contraceptive
 Peri-conceptional alcohol consumption by
mother
 Exposure to radiation
 Low socio-economic status

19. Clinical Features
 DS is a multisystem disorder that affects the
individual physically, medically and
psychologically.
 These patients have a wide array of signs and
symptoms like –
 intellectual and developmental disabilities or
neurological features
 congenital heart defects
 gastrointestinal (GI) abnormalities
 characteristic facial features, and abnormalities.

20. Physical appearance
 Brachycephaly (disproportionately shorter or
small head or skull shape)
 Unusually round face
 Short neck
 Small ears
 Flat nasal bridge
 Microgenia (an abnormally small chin)
 Macroglossia (protruding or oversized
tongue) due to small oral cavity, small chin.

21.  Almond shape to the eyes caused by an
epicanthic fold of the eyelid and oblique
palpebral fissures.
 Other features include shorter limbs
 A single transverse palmar crease (a single
instead of a double crease across one or both
palms)
 Lax ligaments, excessive space between
great toe and second toe
 Dry skin, muscle hypotonia (poor muscle
tone) and brachydactyly (shorter fingers and
toes).

23. Ocular and visual features
 High refractive errors (when the eye cannot
clearly focus image from the outside world)
 Amblyopia (lazy eye) and strabismus (crossed
eye)
 Accommodative and vergence anomalies,
ptosis, blepharitis (eye lid inflammation),
nasolacrimal duct obstruction
 Nystagmus

24.  Keratoconus (conical cornea)
 Brushfield’s spots(speckling of the iris)
 Cataracts
 Glaucoma and retinovascular anomalies

28. Neurological disorders
 Reduced brain volume especially
hippocampus and cerebellum
 Hypotonia (defined as low resting muscle
tone, has been reported in nearly 80% of
new-borns with DS)
 Because of hypotonia Down syndrome
patients have joint laxity that causes
decreased gait stability and increased energy
requirement for physical exertion.
 Five percent to 13% of children with Down
syndrome have seizures

29.  Forty percent of patients with Down
syndrome develop tonic - clonic or
myoclonic seizures in their first 3 decades.
 Lennox - Gestaut syndrome is also seen to be
more prevalent in children with Down
syndrome.
 Dementia occurs more commonly in patients
older than 45 years of age with Down
syndrome.

30.  The risk of developing early-onset Alzheimer
disease is significantly high in patients with
Down syndrome with 50% to 70% of patients
developing dementia by the age of 60 years.
 Nearly all the patients with Down syndrome
have mild to moderate learning disability.

31. Diagnosis

33. Diagnosis
 Screening and diagnostic tests.
 The prenatal screenings do not give definite
results but provide the probability of a foetus
having DS
 If screening test gives a positive finding for
DS, a pregnancy may have DS, a diagnostic
test is performed to confirm if the baby
actually has DS.

34.  There are different methods used for the
prenatal diagnosis of Down syndrome.
Ultrasound between 14 and 24 weeks of
gestation
 Amniocentesis and chorionic villus sampling
 FISH(fluorescent in situ hybridization), QF-
PCR (quantitative fluorescence PCR), and
MLPA(multiplex probe ligation assay)- also
used for prenatal diagnosis.

35.  A relatively new method called as Paralogue
Sequence Quantification (PSQ) uses the
paralogue sequence on Hsa21 copy number.
 It is a PCR based method that uses the
paralogue genes to detect the targeted
chromosome number abnormalities which
are known as paralogue sequence
quantification.

36.  There are non-invasive prenatal diagnostic
methods which are being studied to be used
for the diagnosis of Down
syndrome prenatally.
 These are based on the presence of foetal
cells in the maternal blood and the presence
of cell-free foetal DNA in the maternal serum.

37.  Few other recent methods like digital PCR
and next-generation sequencing (NGS) are
also being developed for the diagnosis of
Down syndrome

38. Management

39. American Academy of Paediatrics
(AAP)

41. Management
 The management of patients with Down
syndrome is multidisciplinary.
 New-born with suspicion of Down syndrome,
should have a karyotyping done to confirm
the diagnosis.
 The family needs to be referred to the clinical
geneticist for the genetic testing and
counselling of both the parents.

42.  Parental education is one of the foremost
aspects regarding the management of Down
syndrome, as parents need to be aware of the
different possible conditions associated with
it so that they can be diagnosed and treated
appropriately.
 Treatment is basically symtomatic and
complete recovery is not possible.

43.  These patients should have their hearing and
vision assessed and as they are more prone to
have a cataract, therefore timely surgery is
required.
 Thyroid function tests should be done on a
yearly basis and if deranged should be
managed accordingly.

44.  A balanced diet, regular exercise, and physical
therapy are needed for the optimum growth and
weight gain, although feeding problems
do improve after the surgery.
 Cardiac referral should be sent for all the
patients 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.

45.  Clinical geneticist - Referral to a genetics
counselling program is highly desirable
 Developmental pediatrician
 Cardiologist - Early cardiologic evaluation is
crucial for diagnosing and treating congenital
heart defects, which occur in as many as 60%
of these patients
 Pediatric pneumonologist -Recurrent
respiratory tract infections are common in
patients with DS.

46.  Ophthalmologist
 Neurologist/Neurosurgeon – As many as 10%
of patients with DS have epilepsy; therefore,
neurologic evaluation may be needed
Orthopedic specialist
 Child psychiatrist - A child psychiatrist should
lead liaison interventions, family therapies,
and psychometric evaluations
 Physical and occupational therapist
 Speech-language pathologist
 Audiologist

47. Assessment
 When recording history from parents, the
clinician should include the following
 Parental concern about hearing, vision,
developmental delay, respiratory infections, and
other problems
 Feeding history to ensure adequate caloric
intake
 Prenatal diagnosis of Down syndrome
 Vomiting secondary to GI tract blockage by
duodenal web or atresia (closed or absent orifice)

48.  Absence of stools secondary to Hirschsprung
disease(nerve cells in the colon don’t form
completely).
 Delay in cognitive abilities, motor development,
language development (specifically expressive
skills), and social competence
 Arrhythmia, fainting episodes, palpitations, or
chest pain secondary to heart lesion
 Symptoms of sleep apnea, including snoring,
restlessness during sleep, difficulty awaking,
daytime somnolence, behavioral changes, and
school problems

49.  Symptoms of atlanto-axial instability include
the following:
 About 13-14% of patients have radiographic
evidence of atlanto-axial instability but no
symptoms
 Only 1-2% of patients have symptoms that
require treatment
 Symptoms include easy fatigability, neck
pain, limited neck mobility or head tilt,
torticollis, difficulty walking, change in gait
pattern, loss of motor skills, incoordination,
clumsiness, sensory deficits, spasticity.

50.  Hyperreflexia, clonus, extensor-plantar reflex,
loss of upper-body strength, abnormal
neurologic reflexes, change in bowel and
bladder function, increased muscle tone in
the legs, and changes in sensation in the
hands and feet
 Physical Examination
 Clinical Features

51. Assessment tools
 Test of infant motor performance
 Alberta infant motor scales
 Peabody development scales
 Gross Motor Function Measure
 Pediatric Evaluation of Disability Index
 Pediatric Balance Scale

52. Motor Development

53. Physiotherapy Management

54.  Some of the common issues that
physiotherapists will address are:
 Delayed developmental milestones
 Impaired Balance
 Decreased strength
 Reduced levels of physical activity
 Sensory Deficits
 Reduced mental health and emotional well-
being

55. Major Goal
 The general goal is to maintain alignment
and encourage normal movement forces to
promote optimal biomechanical forces for
best musculoskeletal development and
prevention of anticipated malalignment and
instabilities.

56. Learning Differences
 Generally, children with intellectual disabilities
such as Down syndrome have been found to:
 Be capable of learning
 Benefit from frequent repetitions in order to
learn
 Have difficulty generalizing skill
 Need more frequent practice sessions in order to
maintain learned skills
 Need extended time to respond, and
 Have a more limited repertoire of responses

57.  Intervention must include an understanding
from a functional, dynamic systems perspective
 The general goal is to anticipate gross and fine
motor delay and provide interventions to
minimize it by:
 Teaching the caregivers appropriate positioning
and handling activities to use throughout early
infancy and childhood to promote antigravity
control and weight bearing.

58.  Designing activities to encourage the
development of antigravity muscle strength
in all positions,
 Emphasizing trunk extension and extremity
loading, which tend to increase axial muscle
tone,
 Encouraging the emergence of righting and
postural reactions through use of rotation
within and during movement,
 Encouraging dynamic rather than static
exploration of movement,

59.  Facilitating the emergence of developmental
milestones when chronologically appropriate,
including supported sitting and standing,
when trunk control and alignment are able to
be established
 Anticipating the delay in postural control
responses and providing functional
opportunities to enhance development in
areas of cognition, language, and
socialization,

60.  Teaching parents and other team members
activities and position choices that will
enhance the child’s overall development.
 Suggestions include:
 Use of aligned compression or weight-
bearing forces to stimulate longitudinal bone
growth as well as thickness and density of the
bone and shaft.

61.  Aligned, supported weight bearing to
promote joint stability.
 Facilitation of muscular co-contraction, force
production, and increased muscle tone.
 Therapists should avoid exaggerated neck
flexion, extension, rotation, and positions or
movements that may cause twisting or undue
forces.

62.  With caution, joint approximation or
compression of the cervical spine should be
performed gently but these activities are
contraindicated in children with identified
atlantoaxial instability.
 Extreme caution must be taken, and any
activity that may result in cervical spine injury
should be avoided.

63. Motor Learning Considerations
 Reduce hands-on support when safe, to avoid
dependence.
 Practice new skill in new environment.
 Provide visual and tactile cues.

64. Sensory Integration Therapy

65. Sensory Integration Therapy

66. Neuro Developmental
Technique
 NDT is an approach which focuses on the
quality of movement and coordination rather
than individual muscle group function
 This hands-on approach is achieved by the
physiotherapist having several ‘key points of
control’, including the head, shoulders, trunk
and/or pelvis to guide and alter movement

67. Neuro Developmental Technique

69. Perceptual Motor Training
 PMT incorporates activities which help to
explore balance, coordination and body
awareness and is not skills-based.
 So, rather than being taught a certain skill,
individuals are provided with an environment
in which to explore and determine what their
bodies can do

72. Other Interventions
 TreadmillTraining
 Two-Wheeled BicycleTraining
 Balance training
 GaitTraining
 Strengthening exercise
 Aerobic Exercise
 EnduranceTraining
 Post-surgical Management