A Case of Developmental Delay

Important Terms:
Developmental delay & Global developmental delay (GDD):
Developmental delay not a standard term but GDD is.

GDD is defined as delay in 2 or more of the following

developmental domains:
Gross/fine motor,
Speech/language,
Cognition,
Social/personal, and
Activities of daily living in young children less than 5 years of
age.

Mild Moderate Severe

C.A.-F.A.= <33% C.A.-F.A=34-66% C.A.-F.A= <66%

Other Problms:
Dissociation Deviation

 Difference in rates of  Deviation in usual

development of different
streams
 15% difference in DQ
scores of two domains
sequential acquisition of
developmental milestones
within a developmental
stream

 May or may not be

associated with GDD
Developmental Disability:

 An umbrella term, of which GDD is a part.

 It is diverse group of chronic conditions that are due to mental
and/or physical impairments.

 Dementia:
Loss of mental ability severe enough to interfere with
normal activities of daily living, lasting more than six
months, not present since birth, and not associated
with a loss or alteration of consciousness.
Intellectual Disability:
The following 3 criteria must be met:
1. Deficits in intellectual functions: reasoning, problem-
solving, planning, abstract thinking, judgment, academic
learning and learning from experience, confirmed by
both clinical assessment and individualized, standardized
intelligence testing.

2. Deficits in adaptive functioning : failure to meet

developmental and socio-cultural standards for personal
independence and social responsibility.

3. Onset of intellectual and adaptive deficits during the

developmental period.
Intellectual disability:
 Without ongoing support, the adaptive deficits limit
functioning in one or more activities of daily life, such as
communication,social participation and independent
living, across multiple environments, such as home,
school, work and community.

 The various levels of severity are no longer based on the

intellectual quotient (IQ) but are, rather, defined by
adaptive functioning .
Developmental Quotient:
Calculated as Developmental age/ Chronological age X 100

 Intelligence quotient:
 A numeric expression of a person's intellectual level as measured
against the statistical average of his or her age group.

 It is determined by dividing the mental age by the

chronologic age and multiplying the result by 100.

 Average IQ is considered to be 100.

A Case of Developmental Delay
 Case preparation
 Case presentation
Case Preparation
Case may be in the form of:
 Developmental delay is the only complaint.

 Delay is associated with other neurological or systemic

symptoms.
 Incidentally diagnosed delayed development.
History
 Exact age of onset / age at which mother first appreciated a
delay.

 Ask about major milestones in each field that mother can

remember; based on this an approximate mental age can be
calculated.

 History should be able to tell us about onset, progression and

severity of the delay.

 Ask about other neurological symptoms like seizures,

unconsciousness, any episodic nature and behavioral traits.
Domain specfic inquiry
 Do you have any concerns about how your child talks and makes
speech sounds?
 Do you have any concerns about how your child understands what you say?
 Do you have any concerns about how your child uses his or her hands
to do things?
 Do you have any concerns about how your child walks or runs?
 Do you have any concerns about how your child behaves?
 Do you have any concerns about how your child gets along with others?
 Do you have any concerns about how your child does things for him or
herself?
 Do you have any concerns about your child’s learning?
 Do you have any concerns about your child’s hearing or vision?
History
 Focus on milestones which are-
1. easily remembered

2. temporally current

3. provide data on type of delay (static, progressive, acute)

 List of useful milestones:

• Social smile Recognition; stranger anxiety

• Walks independently Scribbles spontaneously
• Runs Specific Ma-ma, Da-da
• Jumps Walks up and down stairs
RISK FACTORS FOR POOR
DEVELOPMENT:
BIOLOGICAL FAMILY AND SOCIAL

 Prenatal  Poverty
 Perinatal  Education

 Neonatal  Neglect, abuse

 Postnatal  Stimulating environment

History:
 A detailed family history (up to 2 generations) is
required in cases of suspected genetic/ metabolic
diseases.

 Risk of lead exposure should be assessed from

occupational/ environmental history (young age, old
house, pica, occupation, smoke etc.)
Consanguinity:

A consanguineous marriage is defined as a union between

two individuals who are related as second cousins or
closer, with the inbreeding coefficient (F ) equal or
higher than 0.0156 (Bittles 2001), where (F) represents a
measure of the proportion of loci at which the offspring
of a consanguineous union is expected to inherit
identical gene copies from both parents.
degree of consanguinity:
Degree of Percentage of shared Relationship
Consanguinity genes

First Degree 50% Parents, Siblings,

Children

Second Degree 25% Grandparents, Uncle,

Aunt, Nephew,Niece,
Half sibling

Third Degree 12.5% First Degree cousin

3.1% Second degree cousin

Some clues from History:
 Consanguinity indicates a genetic etiology.

 Most metabolic disorders show neuroregression pattern.

 There is no problem in differentiating a static disorder from a

fast progressive disorder or neuro-regression presenting late.

 Problem arises when there is a slowly progressive disease. In

such cases DQs measured at intervals of 3-4 months will help.

 Symptoms of grey and white matter diseases overlap in first 2

years of life.
 DEVELOPMENTAL
EXAM

ACUTE
DELAY DQ=100

DQ=50 PROGRESSIVE DELAY

DQ=50 STATIC
DELAY
Normal Pattern
Static insult to developing Brain (C.P.)
Prenatal Onset
total lack of development
Early Onset Slow Course
Childhood Onset Rapid Course
Late Infantile or Childhood onset Acute Non-
Progressive Course
Streams of development:
NEUROCOGNITIVE Linguistic, Non verbal visual-motor,
social and adaptive

NEUROMOTOR gross motor, fine motor

NEUROBEHAVIORAL attention, impulsivity, activity

Pattern of developmental delay in various disorders

Disorder Gross motor Fine motor Social Language

Mental + + to ++ ++ to +++ +++
retardation (ID)

Cerebral palsy +++ ++ + +

with mild MR

CP with MR +++ +++ +++ +++

Hearing -- -- -- +++
impairment
Impaired vision -- ++ -/+ --

SMA +++ +/++ -- Receptive

normal,
expressive may
be delayed
PRACTICE QUESTIONS:
DEVELOPMENT:
Approach to a child with delayed speech.

Cause and approach to a preschool child with

developmental regression.
Developmental screening tests for Indian children.

Define developmental delay and developmental

dissociation.
PSYCHOLOGY:
Rumination, Pica

Childhood depression

Clinical manifestations, diagnosis and management of:

ASD, ADHD
DEVELOPMENTAL EXAMINATION:
 It combines informal and structured observations.

 Crucial to note qualitative information, how a task is

done, rather than being over-focused on success/failure
on a domain-specific activity.

 Simultaneous information is gathered about multiple

domains

 Important to decide about vision and hearing early.

4 useful steps:
1. Recollect age specific milestones in the domain you are
going to examine (typical development).
2. Elicit the parental concerns.
3. Observe and confirm.
4. Decide about the presence of delay and severity.

Importnat to remember cut-off-age limits to decide about

significant delay. e.g. not reaching for an object/not
showing interest in objects at 6 months of age.
Motor development in an 18 months old:

ₒ
BED-SIDE TOOLS REQUIRED:
 Torch
 Dangling red ring 6.5 cm
diameter
 Red ball 5.0 cm diameter
 Ten 2-5 cm sized colourful
cubes
 Temple bell
 Rattle 100001996-Bayley4-kit-assessments-1-size-W530-tablet.jfif

 Cup with handle

 Bunch of keys
 Pellets or beads
 Picture book
 Crayons and paper
 Percussion hammer
Examination:
 Sequence of neurological examination should be flexible,
depends on age of the child, his level of cooperation.
 Starts with observation done during history taking.

 Further course can be decided based on child’s age:

I. First 2 months.

II. 2 months- 2 years.

III. More than 2 years.

First 2 months:
 Essentially it is the examination of newborn.
 Done under following heads:
1. Observation
2. Cranial vault examination.
3. Developmental reflexes.
4. Motor function ( tone, strength, tendon reflexes, jitteriness,
plantar reflex; look for any asymmetry)
5. Cranial nerve exam: Almost all cranial nerves can be assessed.
Cranial nerve Examination:
1. Olfactory: Infrequently tested, but can be done using
different aromatic substances like cinnamon (dal-chini) and
cloves (loung).
Response: arrest of activity, sucking, arousal.
Present above 32 weeks.

2. Assess eyes for II, III, IV, VI.

3. VII N. by facial examination.
4. VIII N. hearing difficult to assess. Vestibular function
assessed by oculo-vestibular reflex.
5. IX, X, XII : Assessed by quality and pitch of cry. Beware of
central depression.
6. V, VII, IX, X XII: Involved in sucking and swallowing
Preterm Baby Examination
 Additionally involves examination for neurological criteria for
gestational age assessment.
I. Posture.
II. Head lag
III. Arm recoil
IV. Scarf sign
V. Square window
VI.Leg recoil
VII.Popliteal angle
VIII.Ankle dorsiflexion
IX.Heel to ear
X. Ventral suspension
Assessment of tone:
1. Abnormal posture of limbs
2. Palpation of muscles: Firm or flabby
3. Range of movements
4. Resistance encountered at major joints
5. Shaking the unsupported limb for range and faility or
stiffness of movements.
2 months – 2 years
 Done in 4 stages.
 Can be applied to some children above 2 years of age.

 Older children can be examined in the formal way.

Stage Child’s position Examination

I Mother’s lap Observation
II Mother’s lap Head, DTR, tone, sensation including vision,
hearing, plantar reflex

III Table Other systems, mouth, tongue, OFC

IV Floor Crawl, walk, running.

Examination (few points to remember)
 Abnormality in muscle tone and/ or posture is a must for
diagnosing CP.
 Most syndromes and chromosomal disorders have dysmorphic
features.
 Parents’ perception of normal hearing and normal cognitive
ability may not be reliable and must always be confirmed by
physical examination and investigations.
 Presence of primitive reflexes at grown up age indicates
cortical damage/ defect.
 DQ less than 70% is highly unlikely to be due to secondary
systemic causes.
Case Presentation:
Standard sequence of case presentation is as follows:
1. Demography
2. Presenting complaints
3. History of presenting complaints
4. Past history, including contact history
5. Antenatal history
6. Birth history
7. Postnatal history
8. Development history
9. Nutrition
10. Family history
11. Socio-economic history
12. Immunization
13. History of allergies
Case presentation:
 Introduction of the case is of utmost importance.
 It should provide a line of thinking to the listener.
Case Presentation
Developmental delay is the only complaint:
Introduce the case.

Can be introduced in one of the following ways:

 Child brought for evaluation of delayed development/ not
developing as well as his peers or sibs / mother is concerned
about his development. Mention consanguinity.

 Details of the presenting complaint should include

developmental history and presence or absence of other
neurological symptoms like seizures, loss of consciousness,
abnormal movements etc.
Case Presentation:
Delay is associated with other neurological or systemic
symptoms:
Example is a case of C.P. or neurodegenerative disease.
Can be introduced as:
Chief complaints of developmental delay with seizures/ abnormal
movements/ associated co morbidities like fever, diarrhea etc.

If child is young ,is a case of SBA or preterm with C.P. and has
problems since birth, details of presenting complaints can
begin with birth history.
Incidentally Diagnosed Delayed Development:

Example: Down syndrome with CHD and CCF, CRS,

chromosomal abnormalities etc.
Introduce the case in a routine way with emphasis on the chief
systemic illness.
Developmental delay part to be addressed in developmental
history.
 When history is long over years, treatment taken in between
can be mentioned collectively at a single point of time.

 Past investigations should be mentioned as they were

communicated to the parents.

 History presentation should be able to convey the degree of

dysfunction, severity of illness.
Presentation of Examination Findings:

 Describe general physical examination with emphasis of

dysmorphism, malformations, neuro-cutaneous markers and
nutritional status.
Presenting Neurological Examination Findings:
1. Done under all the usual headings of nervous system
examination.
2. Describe elaborately:
 Higher mental functions including speech, behaviour,
 Motor cranial nerves, vision, hearing,
 Tone, posture (predominant), tendon reflexes,
developmental reflexes, abnormal movements, gait (if
possible).
 Describe180 ͦ examination findings.
3. Power may not be described in the conventional way.
Describe child’s ability to perform voluntary
movements.
4. Description of any gross asymmetry is very important.
Presenting Neurological Examination
Findings:
1. Handedness
2. Higher cortical functions including speech
3. Signs of meningeal irritation
4. Cranial nerves
5. Motor system
6. Sensory system
7. Reflexes
8. Co-ordination
9. Stance
10. Skull and spine
MOTOR SYSTEM SENSORY SYSTEM

 Position  Pain
 Bulk  Light touch

 Fasciculations  Position sense

 Involuntary movements  Vibrations

 Tone  Stereognosis,

 Power graphaesthesia
 2 point discrimination
Diagnosis:
Possible diagnoses:
1. ---- C.P., microcephaly, GDD, epilepsy (type), PEM grade , ----
(associated co-morbidity).
2. GDD, optic atrophy, epilepsy, probably genetic / chromosomal
with ----.
3. Neurodegenerative disorder, white/grey/ mixed involvement,
micro/macrocephaly/ epilepsy with----.
4. GDD secondary to infection ( CRS, meningitis, encephalitis)
importance of developmental diagnosis:
Establishing a diagnosis enables us to answer questions on:
why it has happened (aetiology),

what does it mean for our child (prognosis),

what treatments might be available (precision medicine)

and

whether it can be prevented in the future (prenatal testing

and preimplantation genetic diagnosis).
CLINICAL CLUES: Behavioral
Type of behavior Possibilities

Happy, excitable Angelman syndrome

Repetitive hand stereotype Rett syndrome

Overfriendliness, hypersocial William syndrome

Autistic features Fragile X syndrome, 15 q duplication

Hyperphagia Prader willi syndrome

 Clinical clues: Signs
Signs Possibilities
Hepatosplenomegaly Gaucher, GSD, MPS, Neimann Pick

Hair abnormality Fine hair: Homocystinuria

Friable: Menkes, ASA deficiency
Premature grey: Ataxia Telengiectasia
White Hair: Methionine metabloism
Hearing loss Mitochondrial, Refsum disease

Hyperacusis Tay Sach disease, GM1 gangliosidosis, Krabbe

disease
Café Au Lait macules NF, Bloom syndrome, ataxia telengiectasia

Excessive Mongolian spots GM1 gangliosidosis

Depigmented nevi Tuberous sclerosis

Eczema PKU

Malar flush Homocystinuria

Photosensitivity Hartnup disease

Synophrys Cretinism, Cornelia de Lange syndrome

Grey matter V/S White matter Disease
Grey Matter Diseases White Matter Diseases

Involve processing centers Involve networking of these centers

Neurons affected primarily Axons affected primarily

Neuronal death leads to secondary Myelin destruction or abnormal

axonal degeneration myelin production
Differentiating Features Grey Matter Disease White Matter Disease

Age of onset Usually early( infantile) Late onset (Childhood)

Symptoms Seizures, altered higher mental Ataxia, spasticity, blindness,

functions optic atrophy

Seizures Early, severe Late, rare

Head size Usually microcephaly Can have macrocephaly

Cognitive function Progressive dementia Initially normal

Spasticity Early, severe Later, progressive

Reflexes Normal or exaggerated Absent(neuropathy), hyper

( tracts)

Cerebellar signs late Prominent, early

Peripheral neuropathy Late, Axonal type Demyelinating type

 Contd.
Differentiating Features Grey Matter Disease White Matter Disease

Fundus Retinal degeneration May show optic atrophy

EMG NCV Normal Slow NCV

ERG Abnormal Normal

Evoked potentials(VEP, Usually normal Prolonged or absent

ABR)

EEG Epileptiform discharges Slowing, delta wave pattern

Steps In Evaluation of the Child With GDD
STEP 1:
I. Obtain a detailed history and examination.

II. Do an auditory and ophthalmic screening.

III. Metabolic screening/ T4 if universal screening not done.

IV. Obtain EEG if suspicion of seizures/ epileptic syndrome.

V. Consider screening for autism or language disorder.

STEP 2:

Test positive
Diagnosis
Step 3:
In Short-

Look for clinical characteristics pointing toward a

specific etiology and order testing for that diagnosis first.

When no apparent cause can be identified, a stepwise

approach—conducted in collaboration with a geneticist—is
recommended,
Diagnostic yield of various tests:
Test Diagnostic yield (%)

Neuroimaging
•MRI, non enhanced 55.3%

•CT scan 39%

Genetic studies
• Micro array based techniques 15-20%
•Routine cytogenetic studies (G banding 3.7%
karyotype)
•Subtelomeric deletion 6.6%
•Fragile X screening 2.6%
•MECP2 Unknown
Metabolic testing (Urine organic acids, 1% ( if UNS done)
serum amino acids, serum lactate,
ammonia, blood gas)
Thyroid screen 0-4% (depends on UNS)

Serum lead level Unknown

EEG Approx 1%
CLINICAL SUSPICION
GENETIC INVESTIGATIONS
Large deletion, duplication
(>5million base pair)
Known microdeletion
syndrome
(< 5 million base pair)
Alagille, Agleman, Di
George
Suspecting a known single
gene disorder
TEST ORDERED REMARKS
Karyotype Not the first line test.
Useful in
•clinically suspected
aneuploidy
•chromosomal
rearrangements
•multiple abortions
FISH/MLPA ( multiple Done if specific probe
ligation-dependent probe available, otherwise
amplification; microarray
Exome sequencing followed Example: Fragile X DNA
by sanger validation (FMR1)
It should be considered as
part of first-line investigation
for boys and girls with
GDD/ID
CLINICAL SUSPICION TEST ORDERED REMARKS

Non characterizable Chromosomal Microarray Single test with best yields

suspected microdeletion (CMA) especially in presence of
syndrome multiple malformations and a
specific diagnosis is not
considered.

• A complex, non specific Whole exome/genome Permits analysis of coding

genetic disorder with sequencing regions for known genes and
multiple differential the identification of causal
diagnoses. mutations in up to 40% of
• A genetically patients with ID.
heterogeneous disorder.
• A suspected genetic May become the first line
disorder where a specific investigation in near future
genetic test is not
available.
• Unsuccessful previous
genetic testing.
Other tests:
Congenital Infections:
Done in appropriate clinical settings.

Neuroimaging:
Nonspecific abnormalities in approximately 30% of
children with GDD/ID but contributes to understanding
the etiology in only 0.2% to 2.2% of cases.
Yield more when abnormal nurological signs are present.

MRI preferred over CT scan.

MRS is indicated in all cases of intractable epilepsy or

developmental regression
other tests (contd.)

EEG:
Uncontrolled epilepsy or epileptic syndromes, such as
Landau-Kleffner syndrome

When there is clinical suspicion of seizures, speech

regression or neurodegenerative disorder
Red flags suggestive of inborn errors of metabolism:

•Family history of IEM or developmental disorder or unexplained neonatal

or sudden infant death

•Consanguinity, Failure to thrive

•Head circumference or stature growth abnormality (>2 SD above or under

the mean)

•Recurrent episodes of vomiting, ataxia, seizures, lethargy, coma

•History of being severely symptomatic and needing longer to recover with

benign illnesses (e.g., upper respiratory tract infection)

•Unusual dietary preferences (e.g., protein or carbohydrate aversion)

•Regression in developmental milestones

•Behavioural or psychiatric problems (e.g., psychosis at a young age)

IEM (Contd.)

•Movement disorder (e.g., dystonia)

•Facial dysmorphism (e.g., coarse facial features)

•Organomegaly

•Severe hypotonia

•Congenital nonfacial anomalies

•Sensory deficits, especially if progressive (e.g. catracts, retinopathy)

•Neuroimaging abnormalities

•Progressive spine deformities

Creatine transporter defects, Mild homocystinuria, Female ornithine

transcarbamylase deficiency) can initially present as GDD alone
Laboratory investigations for unexplained GDD/ID:
Blood* Urine*
•Complete blood count Organic acids
•Glucose
Creatine metabolites
•Blood gas Purines, pyrimidines
•Urea, creatinine
Glycosaminoglycans
•Electrolytes (to calculate anion gap)
•AST, ALT
•TSH
•Creatine kinase
•Ammonia
•Lactate
•Amino acids
•Acylcarnitine profile, carnitine (free and total)
•Homocysteine
•Copper, ceruloplasmin**
•Biotinidase***
•Ferritin, vitamin B12 when dietary restriction or pica are present
•Lead level when risk factors for exposure are present
tandem mass spectroscopy (tms)

Sample Used:
DBS

Disorders Detectable:
Disorders of Aminoacids
Urea cycle disorder
Carnitine metabolism defects
gas chromatogrpahy with mass spectroscopy
(gc-ms)

• GC separates components of mixture; MS identifies each component

• Primarily done on urine sample.
• Other tissues: Plasma, serum CSF.
• Disorders detected: Organic acids related disorders
HPLC:

1. Amino acid analysis (plasma, urine, CSF)

2. Purines, pyrimidines in urine
3. Vitamin levels
4. Porphyrins
5. NT in CSF
6. Hemoglobinopathies
7. Various drug levels
IEMs (Treatable/Partially treatable)
 Dietary supplements (folinic acid for cerebral folate deficiency,
pyridoxine or pyridoxal phosphate for B6-responsive epilepsy, creatine
in creatine transporterdeficiency, uridine in pyrimidine 5-nucleotidase super
activity)

 Dietary restriction (homocystinuria, glutaricacidaemia)

 Keto-genic diet (pyruvate dehydrogenase deficiency, Glut1 transporter

deficiency).

 Haematopoietic stem cell transplantation (mucopolysaccharidoses,

metachromaticleucodystrophy),

 Enzyme replacement (Fabry’s disease, Gaucher's disease, neuronal ceroid

lipofuscinosis)

 Gene therapy (adrenoleucodystophy, lysosomal storage disorders).

EXAMPLES:
CATEGORY EXAMPLE

Chromososmal Down syndrome

Single gene disorder (Syndromic) Fragile X Syndrome, Rubinstein Tyabi

syndrome

Single gene disorder ( Non syndromic) OPHN (oligophrenin)1, FMR 2, SLC6A8

Metabolic PKU, galactosemia

Acquired TORCH, HIE, Prematurity, menigitis

practice questions:
 Preventable and treatable causes of mental retardation.
 Physical features assocaited with specific syndromes of
mental retardation.
 Role of pediatrician in adoption.
 Child abuse and neglect: definition, management and
prevention
 Karyotyping.
Further readings:
 Swaiman’s pediatric neurology
 Forfar textbook

 Bickerstaff’s Neurological examination

 De Jong’s Neurologic examination