TYPICAL DEVELOPMENT AND DEVELOPMENTAL DISABILITIES

Tyler Reimschisel, MD, MHPE

 
Child development is a continuous process of acquiring new and advanced skills. A
thorough understanding of child development is a cornerstone of clinical pediatrics. All
physicians who care for children need to understand the principles of typical child
development and have a working knowledge of key developmental milestones. This
knowledge also serves as the starting point for understanding developmental disabilities
in children. In this lecture we will discuss postnatal brain maturation and its relationship
to child development, the five domains of development, and the typical milestones and
red flags for each of these domains. We will conclude with a discussion of three
developmental disabilities that are common in the pediatric population – cerebral palsy,
intellectual disability, and autism spectrum disorders.
 
Child Development Concepts
Child development is a continuous process of acquiring new and advanced skills. This
development depends on maturation of the nervous system, which we will discuss in
more detail momentarily. Although typical child development follows a relatively
consistent sequence, it is not linear. Instead, there are “spurts” and “lags.” For
example, motor development in the first year of life proceeds relatively rapidly – babies
typically mature from being completely immobile to walking in just over 12 months, but
then motor development during the second year is less dramatic. Conversely, language
development in the first year of life occurs slowly, but there is an explosion of language
acquisition between a child’s first and second birthdays.
 
On average, most children achieve each developmental milestone within a defined and
narrow age range. There are multiple tables that list key developmental milestones and
the average age at which these milestones are achieved (review Appendices A and B).
However, it is essential to remember that each developmental milestone can be
acquired within an age range. Most of your tests (STEP and Boards) will test your
knowledge of the average age at which a developmental skill is obtained. However, I
think that it is much more clinically useful to know how late a child can acquire a skill
and still be within the typical range (within two standard deviations of the mean). These
so-called “red flags” are important because they can be used to identify when a child
has developmental delay for specific skills. For example, although the average age of
walking is approximately 13 months, a child may walk as late as 17 months and still be
within the typical developmental range. In this example, the “red flag” for independent
walking is 18 months, and a child who is not walking by 18 months of age is delayed.
 
Brain Maturation and Child Development
The postnatal human brain undergoes significant growth and maturation during the first
two years of life, and these changes determine when children acquire developmental
skills. The average adult brain weighs approximately 1400 grams, but the newborn
brain weighs only 400 grams. Therefore, after birth the human brain more than triples in
weight. Most of this growth is achieved during the first two years of life. Typically, by

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our first birthday our brains weigh 1000 grams, and by two years of age our brains have
reached 80% of their adult size.

Microscopic neuronal growth and modeling is

even more dramatic. Whereas prenatal brain
development is characterized by neuronal
proliferation and migration, neuronal
proliferation is nearly complete by 36 weeks
gestation. However, after this time there is
significant elaboration and proliferation of
dendritic and axonal processes and
connections. These changes, including
dendritic arborization, synaptogenesis, and
axonal connections, account for most of the
brain’s postnatal growth.

The last developmental process that contributes to bring growth and maturation is
myelination. Larsen nicely summarizes the myelination process and its impact on child
development.

Myelination begins early in the third

trimester with the most rapid period of
myelination occurring in the first two
years of life. The myelination process
follows a specific time course and
pattern. The acquisition of
neurodevelopmental milestones parallels
and reflects this pattern. Myelination
occurs early in motor-sensory roots,
special senses, and the brainstem; those
structures necessary for reflex behavior
and survival. The corticospinal tract starts
to myelinate at 36 weeks gestation, and
myelination is completed by the end of the
second year of life. Myelination of the
corticospinal tract begins at the proximal
portion of the axon and the shortest axons
are the first to myelinate. The axons for
the upper extremities and the trunk
myelinate next. The axons for the lower
extremities, which are the longest, are the
last to myelinate with the process being
completed by 24 months of age. This
myelination pattern correlates with the progressive head-to-toe acquisition of
developmental milestones. The motor patterns of the immature brain are
predominantly under brainstem control and lack cortical modulation until there is

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 necessary maturation of these higher brain center connections. (Larsen PD and
Stensaas SS at library.med.utah.edu/pedineurologicexam/html/dev_anatomy.html)

 I want to emphasize that the growth, maturation, and myelination of the brain
directly correlate with the acquisition of developmental milestones in babies and
young children. Thus, delayed development is a symptom of an underlying disorder of
brain growth, maturation and/or function.

Developmental Domains
The range of child development can be divided into multiple developmental “domains”
or “streams.” There are several different methods for categorizing these domains, but I
typically consider childhood development in 5 domains: gross motor, fine motor (visual-
motor and problem solving), receptive language, expressive language, and social-
adaptive. Gross motor development involves the coordination of large muscle groups.
Examples of gross motor milestones include sitting, crawling, and walking. Fine motor
development involves the function of small muscle groups and their coordination with
the visual system. Examples of fine motor skills include feeding ourselves, coloring,
and writing. Receptive language development involves comprehension of language that
is spoken, written, or signed. Examples of receptive language skills include
understanding the word “no” and following commands. Expressive language
development involves expressing our needs, wants, and thoughts through language that
is spoken, written, or signed. Examples of expressive language skills include learning
to speak or sign words and putting words together to formulate sentences. Social-
adaptive development involves learning behaviors that are important for interacting
successfully with others. Examples of social-adaptive skills include playing games with
other children. Though this delineation of development into specific domains is clear
and well organized, it is important to acknowledge the specific skills frequently require
integration of multiple domains. For example, becoming toilet trained, a social-adaptive
skill, requires maturation of gross and fine motor skills as well as advanced language
skills because the child must tell an adult that he or she needs to use the restroom.

Gross Motor Domain

Based on our earlier discussion about neuronal maturation and myelination patterns, it
should not be surprising that motor development proceeds in a predictable sequence.
Babies acquire motor skills from cephalad to caudad (they learn to use their arms
before they learn to use their legs) and from proximal to distal (they learn to control their
head before they learn to use their fingers). Furthermore, babies respond to stimuli in a
symmetric reflex, but these reflexes must extinguish before voluntary, asymmetric, and
discrete movements can be acquired. For example, the Moro reflex is present at birth
but begins to diminish as the child learns the asymmetric tonic neck reflex. The
asymmetric tonic neck reflex then extinguishes as the older child is able to initiate
discrete voluntary movement. Persistence of primitive reflexes or lack of development
of postural reflexes and voluntary movement can be indicative of upper motor neuron
abnormalities.

The last principle I would like to discuss about motor development is that this domain
has the weakest correlation to cognitive abilities. This is particularly important since

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during the first year of life motor development is the most prominent aspect of a child
development. Therefore, delays in this stream are relatively easily identified in the first
year of life. However, it is very common for parents of babies with developmental delay
to voice concerns that impairment in motor development will place the child at risk for
impairment in language skills or cognitive abilities. However, there is a poor correlation
between motor development and cognition. Therefore, it is not prudent within the first
year of life to use motor development as a predictor for language development or
ultimate cognitive outcome unless the child has been diagnosed with an underlying
neurologic or genetic condition known to be associated with long-term cognitive
disability.

Below is a list of red flags for gross motor development.

 5 mos: does not roll over

 8 mos: cannot sit without support
 < 15 mos: unilateral dominance
 18 mos: not walking
 2 yrs: not climbing stairs
 2.5 yrs: not jumping with both feet
 3 yrs: unable to stand on one foot
 4 yrs: unable to hop
 5 yrs: unable to walk straight line

Significant delays in gross motor skills do place the child at risk for having cerebral
palsy (see below). A common feature of cerebral palsy is abnormal muscle tone,
especially spastic hypertonicity. Therefore, it is important to know the early warning
signs of spasticity, including rolling over too early (at 1-2 months of age), pulling directly
to a stand at or before 4 months of age, hypotonia in the first year of life (frequently
evolves into hypertonicity in the second year of life), W-sitting (a sign of hypotonia of the
pelvic musculature), and persistent toe walking. Individuals with these signs should be
monitored closely for motor impairment or referred to a spasticity or cerebral palsy clinic
for evaluation and management.

Fine Motor Domain (Visual-Motor & Problem-Solving)

I consider this a domain of 3 interrelated components: fine motor skills, visual skills and
hand eye coordination, and problem-solving.

The fine motor skills included in this domain involve manipulation of the arms and
hands. For example, fine motor skills in a baby include transferring objects between
hands, the development of a fine pincer grasp, and scribbling with a crayon. In the first
year of life, fine motor skills are associated with gross motor skills. Beginning in the
second year of life, fine motor abilities may be more closely associated with the
cognitive system.

Problem-solving is included in this domain because we typically test problem-solving

skills in young children by asking them to solve problems using fine motor skills. For

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example, we will assess a child's ability to understand different shapes by determine
whether the child is able to manipulate a circular object into a circular hole in a form
board. Whereas toddlers are learning how to manipulate small objects, as they get
older children learn about objects by manipulating them. In order words, there is
progression from “learning to manipulate" to “manipulating to learn." Since problem-
solving is a component of this developmental domain, impairment in this domain is
loosely correlated with cognition, especially nonverbal intelligence (“toddler’s IQ”).
Finally, this domain is also correlated with social-adaptive function since visual-motor
and problem-solving abilities are used in interactive play among children.

It is important to remember that each of the components in this domain is interrelated

with each other. Therefore skill or deficiency in one area promotes or impedes
development in other areas. Consequently, the examiner must be careful not to draw
inappropriate conclusions about a young child's intellectual disability if that child has
significant impairment motor skills or visual abilities.

Below is a list of red flags for fine motor skills (visual-motor and problem-solving
domain).

 3 mos: unclenched fist

 3.5 mos: persistent grasp reflex
 5 mos: unable to hold rattle
 7 mos: unable to hold object in both hands
 9 mos: no interest in peek-a-boo
 11 mos: absent pincer grasp
 12 mos: does not search for hidden object
 15 mos: unable to put in or take out, no interest in cause and effect games
 2 yrs: not scribbling; not stacking 5 blocks
 3 yrs: cannot draw straight line; 8 block stack

Since this domain includes several neurologic functions (fine motor skills, vision, and
problem-solving), impairment in this domain requires a careful assessment of function in
each of these aspects.

Language Streams
Language development is divided into two broad domains – receptive language and
expressive language. Delays in these streams account for the greatest percentage of
delays in children. These are also the streams that are most closely tied with cognition,
especially verbal intelligence. Therefore, since we lived in a literate society, lifelong
impairment in this domain has the most significant impact on an individual’s life.
Despite the importance of developmental skills in these domains, specific
developmental milestones are very difficult to assess in the clinical setting. Children
who are apprehensive or shy may be to be reluctant to demonstrate their abilities in the
clinic. Therefore, when concerns about language development are raised, time should
be devoted to a careful history of the child's language abilities and other developmental
abilities. Furthermore, children with deafness or less severe forms of hearing loss may

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have impaired speech yet have normal intelligence. This highlights the importance of
remembering that speech is only one aspect of expressive language ability. Therefore,
it is essential that all children with language delay receive a speech and language
evaluation and a hearing test since hearing impairment is a treatable cause of speech
and/or language delay. Children with normal hearing who have language delay should
be referred for formal psychology testing in order to thoroughly assess their verbal and
nonverbal abilities

There are 3 periods of early language development. The first is the Prespeech Period
(0-10 months of age). During this period babies typically acquire the receptive skills of
localizing sound and attending to voices. They also acquire the expressive skills of
cooing (using only a vowel sound, like “oo”), razzing (“blowing bubbles”), and babbling
(using a consonant and a vowel together, such as “bababa” or “dadada”). The second
period is the Naming Period (10-18 months). During this period children acquire the
receptive skills of learning their name and learning the meaning of “no.” The typical
child will understand much more than she can say at this age. Expressive language
milestones that are achieved during this time period include naming objectives and
jargoning (speaking with a tone and cadence that sounds like a language). Typically
children during this period do not have significant growth in their expressive language
skills. Instead, that happens during the final period of early language development, the
Word Combination Period (18-24 months). During this phase there is an explosion of
language acquisition. Typically, by 24 months a child may use up to 50 words, speak in
2-word sentences, and use “giant words” (“hold you”) and holophrases.

As mentioned earlier, delays in these streams are quite common. Children with delays
in the language streams as well as delays in the visual-motor and problem solving
stream suggest possible intellectual disability (formerly called “mental retardation”).
Delays in only the language streams, especially the expressive language stream,
suggests isolated hearing impairment or a communication disorder.

Below are specific red flags in the language streams.

 9 mos: not babbling

 11 mos: not saying “dada” or “baba”
 13 mos: not orienting to name
 18 mos: < 3 words with meaning, not following command
 2 yrs: less than 10-25 words, no 2 word phrases
 3 yrs: does not know own full name, no 3 word phrases, less than half speech
intelligible
 4 yrs: does not understand prepositions
 4.5 yrs: cannot count sequentially
 5 yrs: not using proper syntax, does not know colors

Social-Adaptive Stream
The final stream is the social-adaptive domain. Behaviors manifested in this stream
involve the assimilation of multiple components, including social skills, emotional

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maturity, and adaptive functioning. Social skills are influenced by the child's
temperament, how this temperament fits with the parents’ personalities, parenting style
of the parents, and interpersonal relationships with other family members and friends.
Emotional functioning of the child includes the child's personality, feelings, and how the
child expresses his or her emotions. Adaptive skills include feeding, dressing, toileting,
and other activities of daily living. Development in this stream is greatly influenced by
the child’s environment and by the function or impairment of the other domains.

The manifestation of temper tantrums is an example of a behavior in this domain.

Temper tantrums are common in toddlers. However, they can be exacerbated by the
parental response to the behavior. Although the best response to a temper tantrum is
to ignore it, a parent who is anxious or short-tempered could worsen the behavior by
overreacting to it. Thus, the parent’s personality and style can directly influence the
severity of problems in this domain. Furthermore, controlling the impulses that led to
the temper tantrum is a learned skill. A toddler may have not yet learned this ability, but
a 4-year-old child who has not learned self-control and is still demonstrating temper
tantrums has a significant impairment in this domain or has an underlying
developmental disability that is impeding his ability to learn self-control.

Below are red flags in the social-adaptive domain.

 3 mos: not smiling socially

 6-8 mos: not laughing in social settings
 1 yr: hard to console, stiffens when approached
 2 yrs: kicks, bites, screams, rocks back and forth, no eye contact, lack of social
relationships (ask about and watch play)
 3-5 yrs: in constant motion, resists discipline, does not play with other children
 Be aware of possible pathology in parent(s)

Developmental Delay
With a working knowledge of the five developmental domains and the typical
developmental milestones in these domains, we can begin to consider the approach to
a child with delays in one or more of these streams. First, it is important to reinforce
that development can be affected by both intrinsic and extrinsic factors. Intrinsic factors
that can impair development include chromosomal anomaly or other genetic diseases,
hypoxic-ischemic injury, neonatal infections, exposure to alcohol in utero (fetal alcohol
syndrome or fetal alcohol effects), chronic medical conditions (such as cancer), and
visual or auditory impairments. The extrinsic factors that can affect development
include physical or other forms of abuse, neglect, psychosocial deprivation, family
illness, impaired personalities in family members, cultural influences, and the economic
status of the family.

When there is concern about developmental delay in a child, then a developmental

quotient should be calculated. The developmental quotient is the ratio of the
developmental age of the child to the chronologic age. The developmental quotient
should be calculated for each developmental stream. Typical development is a

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developmental quotient greater than 70%, and atypical development it is a
developmental quotient that is less than 70%. Atypical development is pathologic.
Children with atypical development are at risk for lifelong developmental problems. The
term global development delay is used if a child has a developmental quotient less than
70% in two or more domains. Children with global developmental delay should receive
a thorough medical evaluation to determine the cause of the delay and to begin
management for their developmental disabilities. Note that we will discuss the
evaluation and management of global developmental delay later in this lecture.

Sample calculation of the Developmental Quotient: Calculate the developmental age of

a 26-month old that has the following developmental skills: saying “mama,” “dada,” and
“baba” for bottle; taking a few steps independently, feeding herself Cheerios, and not
scribbling. She has had no regression. Her developmental quotient is____________.

Developmental Disabilities
A developmental disability is a life-long and chronic condition due to impairments in
mental and/or physical impairments that impacts the individual’s major life activities,
such as language, learning, mobility, self-help, and independent living. Development
disabilities are quite common. Approximately 16 to 18% of children have a
developmental disability, including behavior problems. Furthermore, approximately 1%
of children have an autism spectrum disorder. Since developmental disabilities are
common, monitoring a child’s development is an essential component of well child care
in clinical pediatrics. Ongoing assessment of the child's development at each well-child
visit creates a pattern of development that is more useful than measuring the discrete
milestone achievements at a single visit; therefore, developmental screening is
completed at each well-child visit. Identification of a child with developmental delays
should be accomplished as early as possible because the earlier a child is identified, the
earlier the child can receive therapeutic interventions that can improve the child's
outcome.

There are several developmental disabilities, including cerebral palsy, learning

disabilities like dyslexia, intellectual disability, autism spectrum disorders, attention
deficit-hyperactivity disorder, hearing impairment, and vision impairment. Given the
time constraints at this lecture, we will focus on just 3 of these developmental
disabilities: cerebral palsy, intellectual disability, and autism spectrum disorders. These
developmental disabilities are impairments in a specific subset of the developmental
domains. Cerebral palsy is predominantly an impairment of gross and fine motor skills,
intellectual disability is primarily an impairment of language, problem-solving, and
social-adaptive abilities, and autism spectrum disorders are primarily disorders of social-
adaptive behaviors.

Cerebral Palsy (CP)

Cerebral palsy describes a group of permanent disorders of the development of
movement and posture. These disorders cause activity limitation and are attributed to
nonprogressive disturbances that occur in a developing fetal or if the brain. Though
primarily disorders of motor function, CP is often accompanied by disturbances of

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sensation, perception, cognition, communication, behavior, epilepsy, and secondary
musculoskeletal problems. The prevalence of cerebral palsy at 8 years of age is
3.6/1000 individuals.

The classification of the types of CP (semiology) is based on the type of tone

disturbance, the limbs that are involved, and the severity of the impairment. CP can
cause hypertonic (spastic), hyperkinetic (dystonic), or hypotonic tone. Of these, the
most common form is spastic cerebral palsy. In spastic CP limbs demonstrate stiffness
or resistance to passive movement, and this resistance increases as the speed of the
passive movement increases. Rapid flexion of the arm will cause more resistance than
slow flexion of the arm. Conversely, hyperkinetic or dystonic cerebral palsy
demonstrates increased tone and a constant amount of resistance despite the rate of
passive motion. The intensity of resistance remains the same regardless of how quickly
the arm is flexed. Hyperkinetic hypertonicity disappears when individuals with
hyperkinetic cerebral palsy are asleep, but this does not occur in individuals who have
hypertonic or spastic cerebral palsy. The final type of CP is hypotonic cerebral palsy,
and this form is much less common. Babies and toddlers with developmental delay
frequently have hypotonia, but this tone typically evolves into spastic, dystonic, or mixed
hypertonicity in the second to third years of life.

Cerebral palsy is also classified according to the limbs that are involved. In individuals
with spastic CP, the arm and leg on one side of the body can show weakness
(hemiparesis) or complete paralysis (hemiplegia), both legs can be weak (diparesis) or
completely paralyzed (diplegia), or all four limbs can be weak (quadriparesis or
tetraparesis) or completely paralyzed (quadriplegia or tetraplegia). Complete paralysis
is very rare; therefore, it is more appropriate to use the terms hemiparesis, diparesis,
and tetraparesis, respectively. In individuals with hyperkinetic cerebral palsy, it is most
common that all 4 limbs as well as the face demonstrate choreoathetotic movements in
addition to dystonic hypertonicity. Finally, individuals with hypotonic CP usually have
decreased tone of all of the limbs as well as the face.

A final method for classifying cerebral palsy is to measure the severity of the motor
impairment. This can be based on the Gross Motor Function Classification System
(GMFCS).

 Level I – walks without limitations

 Level II – walks with limitations
 Level III – walks using a hand-held mobility device
 Level IV- self-mobility with limitations; may use powered mobility
 Level V – transported in a manual wheelchair.

Sample videos of children with CP will be shown in class in order to demonstrate the
classification system of CP.

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 prevalence (per 1000)
200
The most common risk factor for cerebral 146
palsy is premature birth. As noted in this 150
graph, cerebral palsy is quite rare in children 100 62
born after 32 weeks gestational age but has 50
a prevalence of 62/1000 for infants born at 29 7 1.1
0
to 31 weeks gestational age and a very high
<28 w eeks 29-31 32-36 >36 w eeks
prevalence of 146/1000 for infants who were w eeks w eeks
born at 28 weeks gestational age or less.
Gestational age

This graph shows that spastic cerebral palsy

is the most common type of cerebral palsy in 120
preterm

both term and preterm infants. However,

prevalence (%)
100 term
80
hemiplegia is more common in term infants 60
than in preterm infants. This is likely 40
20
secondary to unilateral strokes in term 0
infants, whereas unilateral strokes in preterm

al

ia

ic
ia

a
infants are quite rare. Conversely, diplegic

gi
t

g
eg

st
to

le
le

pa
pl

ip
rip
tic

-s
di
CP is much more common in preterm infants

m
as

ad

on
he
Sp

qu

N
then in term infants. This is likely secondary types
to injury of the cortical spinal tract fibers from
intraventricular hemorrhage, a relatively
common intracerebral hemorrhage in preterm infants.

This figure shows the corticospinal tract fibers in a normal brain,

but the fibers in red are the corticospinal tracts in a preterm
infant who had intraventricular hemorrhage. Note that in
addition to the damaged corticospinal tract fibers, the
thalamocortical fibers carrying sensory input to the cortex are
also significantly abnormal. This may explain the associated
sensory deficits that are seen in individuals with diplegic CP.

This figure shows a computed tomography

scan (A) and a magnetic resonance imaging
scan (B) of a preterm infant with
intraventricular hemorrhage originating in
the thalamus. It is easy to see how
intraventricular hemorrhage in preterm
infants can secondarily damage the
corticospinal tract and the thalamocortical
fibers, leading to diplegic cerebral palsy.

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As mentioned above, there are many comorbidities in individuals with cerebral palsy.
These comorbidities are listed here.

 Neurology: seizures (20-60%)

 Ophthalmology: strabismus, amblyopia (3-24%)
 Otology: hearing loss (0.3-4%)
 Gastrointestinal: constipation, incontinence, obesity
 Orthopedics: scoliosis, hip dislocation, joint contractures
 Psychology: ADHD, learning disabilities, depression
 Endocrinology: short stature, puberty delay
.
It is important that the care of individuals with cerebral palsy includes an assessment for
these potential medical problems and initiation of medical management when indicated.

This leads us to a discussion of the treatment of cerebral palsy. The goals of treatment
include improvement of function (sometimes through the care of others) and the
prevention of deformity that can occur when spastic hypertonia causes joint
contractures and scoliosis. If necessary, nonmedical treatments such as daily physical
activity and range of motion exercises should be provided to individuals with cerebral
palsy. Unfortunately, it is also frequently necessary to use medication or surgery as an
adjunctive to daily exercise in an effort to obtain better tone management.

Medications for CP. There is very little data on the relative efficacy of most of the
medications used to treat cerebral palsy. Oral medications that are commonly used
include benzodiazepines, baclofen, and tizanidine. Other less commonly used oral
medications include clonidine, cyproheptadine, anticholinergics (such as
trihexyphenydyl), and antiepileptics (gabapentin, pregabalin). In some cases, injected
medication can be very effective. For example, botulinum toxin injections can treat
hypertonic cerebral palsy because the toxin produced by Clostridium botulinum blocks
acetylcholine release at the neuromuscular junction and produces a chemodenervation
paresis. This effect is focal and temporary (2-3 months) because it is injected directly
into the overactive muscle and there is little spread beyond the active site. If it does
spread from the active site and the injection was provided in the neck, then swallowing
or breathing problems may develop and can be life-threatening. In addition, botulinum
toxin injections can be very expensive.

In addition to being an oral medication, baclofen can also be administered via an

implantable and programmable pump. The pump is surgically placed in the abdomen,
and a catheter is placed between the pump and the spinal cord. This intervention is
usually used in the management of severe spasticity due to cerebral palsy as well as
hypertonia related to a stroke, brain injury, or spinal cord injury. Most patients are
maintained on a dose of 300-800 micrograms per day. The pump requires periodic
percutaneous refills, and it must be replaced in about 8 years. Finally, about 30% of the
patients have complications. Nonetheless, intrathecal baclofen can be a very effective
method for treating CP.

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Surgery for CP. The next intervention for cerebral
palsy that should be mentioned is selective dorsal
rhizotomy. This surgical interruption of the reflex arc
involves sectioning some of the afferent nerve
rootlets from L2 to S2. Intraoperative EMG is utilized
to determine which rootlets should be interrupted,
and only some of the rootlets at each level are
interrupted. This surgery causes weakness and a
permanent reduction in ton, but there are usually no
sensory deficits. Given the degree of impairment, the
surgery must be followed by extended and intense
therapy.

Finally, in some cases where the impairment is severe or the disability is causing
significant limitations, orthopedic surgery is indicated. All the orthopedic surgeries
attempt to increase function by a) maintaining the appropriate length of muscles via
musculotendinous lengthenings, b) providing power through tendon transfers, c)
improving the mechanics of gait via rotational osteotomies, and d) providing limb
stability via osteotomies and selective joint fusions.

The treatment of cerebral palsy is challenging and frequently requires input from several
different specialists. Like many other institutions, Vanderbilt has a team of
multidisciplinary experts who see patients in our STEP Clinic for children with spasticity
and/or cerebral palsy.

Intellectual Disability (ID)

Intellectual disability is the next disability that we will discuss. This condition was
formerly called “mental retardation.” Intellectual disability is defined as significantly sub-
average general intellectual functioning (IQ less than 70) with limitations in adaptive
functioning in at least two of the following skill areas: communication, self-help, social
skills, academic skills, work, leisure, and health and/or safety. It is very common; the
incidence is 1-3% in the general population. Males are more likely than females to be
affected. It occurs in 1:4000 males, but occurs in only 1:6000 females.

I classically divide the forms of intellectual disability into two categories: mild cognitive
impairment and severe cognitive impairment. Mild ID is an IQ of 50-70. It occurs in 8.4
to 30 per 1000 individuals, and the etiology can be identified in about 30-50% of the
cases. Mild ID is more common in boys and in those with a low socioeconomic status.

Severe intellectual disability is an IQ less than 50. It occurs in 3 to 4 per 1000 children.
The etiology is identified in approximately 75% of the cases. There is no gender
predilection. It is common for individuals with severe ID to have other neurologic
problems, such as seizures (20%) and hearing impairment (50%).

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The pediatric clinician must be aware that intellectual disability can present in various
forms. First, a newborn baby or young child may have characteristic dysmorphic
features of a condition that is associated with intellectual disability. Down syndrome
would be an example of a condition that falls into this category. Next, there may be
medical problems that lead to the diagnosis of a genetic disease that can be associated
with intellectual disability. An example of a condition in this category is William
syndrome in which newborn babies can have congenital heart malformations (especially
aortic stenosis), hypercalcemia, and characteristic facial features. William syndrome is
associated with intellectual disability. Furthermore, it is common for babies to have
heart and/or brain malformations and yet not meet the clinical or laboratory criteria for a
specific, named genetic condition. Nonetheless, even without the diagnosis of a
specific genetic syndrome that can be associated with ID, children with significant brain
or heart malformations are at increased risk for lifelong cognitive impairment. Neonates
and babies with severe epilepsy that does not respond to medication are also at risk for
intellectual disability.

Toddlers or preschool children who are diagnosed with global developmental delay are
also at risk for being diagnosed with intellectual disability at an older age. In general,
the diagnosis of intellectual disability is not made in a toddler or preschool child and less
they have a known genetic condition associated with intellectual disability. In the
absence of a specific genetic diagnosis, the diagnosis of intellectual disability in most
children is made once they are able to complete formal psychology testing at
approximately 5 years of age.

Speech delay may also be a marker of language delay, and any child with speech delay
should be assessed for an underlying language impairment. Finally, children who have
been diagnosed with learning problems in school may in fact have an underlying
cognitive impairment, such as a low normal IQ in the 70s or mild intellectual disability in
the 60s.

In addition to the various presentations for intellectual disability in young children,

conditions that cause intellectual disability can also be associated with comorbidities.
For example, individuals with intellectual disability can have autistic-like features. This
is especially true for individuals with severe intellectual disability. Approximately 20 to
30% of individuals with intellectual disability have cerebral palsy, 15 to 30% have
epilepsy, and 30 to 40% have behavior problems. There is also an increased incidence
of mental illnesses, including anxiety, depression, obsessive-compulsive disorder, and
rarely schizophrenia. Sleep problems are quite common in individuals with intellectual
disability. It is important that the clinician ask about sleep hygiene and problems with
sleep since many families will not volunteer this information as they do not consider
sleep problems a medical condition. Finally, hearing impairment may also be present in
individuals with intellectual disability.

A full medical assessment should be performed for any child with concerns about
cognitive impairment. This begins with a complete history and physical examination. In
the history it is important to determine if the patient has had any neurologic regression.

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Neurologic regression is the persistent loss of previously obtained developmental
milestones. Neurologic regression is seen in neurodegenerative diseases, not
intellectual disability. The evaluation of a child who has experienced neurologic
regression is fundamentally different than the assessment we are discussing today.

For toddlers or preschool children with speech delay, a hearing test his obligatory and
referral to a speech-language pathologist is recommended.

For school-aged children (4-6 years of age) with language delay or other concerns of
cognitive dysfunction, a formal psychology assessment should be completed by a
school psychologist or a psychologist at a child developmental center. As mentioned
previously, unless a baby or young child has the diagnosis of a genetic syndrome
associated with intellectual disability, the diagnosis of intellectual disability is not made
until formal psychology testing can document a sub-normal IQ and adaptive functioning
can be quantified. Occasionally, I will tell the family of a child less than 4 years of age
that their child will likely have intellectual disability when the child's developmental
delays are very severe. If the delays are very severe, I may do this even if the child has
not had a formal diagnosis of a genetic syndrome and before the child is old enough to
complete formal psychology testing. In turns out that children with severe
developmental delays may always be too impaired to perform formal psychology
testing.

A principle goal for the assessment of a child with speech delay, global developmental
delay, or other features suggestive of intellectual disability is to identify the etiology for
the developmental concern. There are a large number of causes of intellectual
disability. In a study by Stevenson et al published in 2003, the etiology for intellectual
disability was identified in approximately 40% of the subjects. Etiologies included
chromosomal anomalies, monogenic disorders, other genetic syndromes, brain injury, in
utero infections, chemical exposure, prematurity, and multifactorial or cultural familial
factors. One could argue that multifactorial and cultural familial factors have an
underlying genetic predisposition. But in these cases, it is likely that the impaired
cognition is multifactorial, including genetic influence from many different genes (not a
monogenic disorder like Fragile X) as well as environmental factors. Perhaps the most
important point of the Stevenson study is the demonstration that over half of the
individuals with intellectual disability had an undiagnosed etiology. Despite an
increased understanding of the genetic factors of cognition and development, it turns
out that I am unable to make an etiologic diagnosis in the majority of children whom I
see in my clinic with global developmental delay, intellectual disability, and autism
spectrum disorders.

The medical management of intellectual disability as well as other developmental

disabilities begins with a disclosure to the family of the clinician’s concern for the
diagnosis. This must be done gently but clearly, and the family can be given time over
a series of visits to process the information that their child has or is at risk for having
lifelong cognitive problems. In addition, any comorbid conditions should be treated or
the primary care physician should refer the patient to the appropriate subspecialist who

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can provide treatment for the comorbid condition. The clinician can also help to
facilitate social, community, or educational supports for the family. These may include
family support groups, national parent organizations, and other resources in the
community for families of children with developed level disabilities.

One of the most important aspects in the management of a child with intellectual
disability is ensuring that the child receives appropriate educational interventions. Early
identification helps to ensure that the appropriate educational intervention can be
initiated sooner. Children less than 3 years old with developmental delays are enrolled
in early intervention programs. Each state has an early intervention program, and the
program in Tennessee is called Tennessee Early Intervention Services (TEIS). It is
comprised of a multidisciplinary team of therapists who do an assessment and provide
appropriate interventions. Their assessment is summarized in a report called the
Individualized Family Service Plan. This Plan serves as the basis for therapeutic
services that are provided by the therapists in the early intervention program team.
Children who are older than 3 years of age receive services through the special
education services within the local school district. These services are also provided by
a multidisciplinary team of therapists as well as a psychologist. They complete an
assessment and summarize their findings in a report called the Individualized Education
Plan (IEP). The IEP serves as the basis for the services that will be provided to the
child within the school system. Federal law mandates that children receive the special
services that they need in the least restrictive environment possible. Therefore, many
children with developmental disabilities are now educated in the regular (“mainstream”)
classroom with an aide instead of being placed in a separate classroom. However,
some children with more significant intellectual or behavioral problems may require
placement in a special education classroom for part or all of the day.

Genetic Evaluation of Developmental Delay and Intellectual Disability. I would like to

briefly discuss the genetic evaluation that I recommend for children with global
developmental delay, intellectual disability or an autism spectrum disorder. First, based
on my history and physical examination, I will perform testing for a recognizable
syndrome if the patient's presentation suggests one of these syndromes. If not, then I
will obtain blood samples for chromosomal microarray analysis and fragile X testing. If
both of these studies are within normal limits, then I will obtain a karyotype to look for
inversions and other balanced rearrangements that cannot be identified using
microarray analysis. I will also frequently perform metabolic studies to screen for inborn
metabolic diseases, but the incidence of inborn metabolic diseases in a child with
nonspecific global developed delay, intellectual disability, or an autism spectrum
disorder is very low (less than 1% of cases). I will perform a brain MRI if the child has
focal abnormalities on the neurologic examination, epilepsy, a movement disorder,
microcephaly, or macrocephaly. I will request an EEG if there are any episodes
suggestive of seizures. The rationale for performing this comprehensive evaluation is
that it can provide information about long-term prognosis, the risk of associated
comorbidities in the future, and recurrence risk information that the family may use for
future family planning.

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Since chromosomal microarray analysis has revolutionized clinical genetics, I will
discuss this test briefly. I perform this test in all children with multiple congenital
anomalies, global developmental delay, intellectual disability, and autism spectrum
disorders. The array is designed to identify submicroscopic deletions and duplications
that can be associated with these developmental disabilities or malformations. The
specific details of an array very between clinical laboratories, and for teaching purposes
The array that is performed here at Vanderbilt includes over two million SNPs. These
SNPs are not evenly distributed throughout the genome. Instead, their position has
been carefully selected. First, there are SNPs they overlap regions known to be
associated with contiguous gene deletion syndromes, such as velocardiofacial
syndrome and Williams syndrome. There is also a concentration of SNPs in the
subtelomere regions because these areas are gene rich and small deletions or
duplications in these areas are more likely to be pathologic than interstitial deletions or
duplications. Depending on the study, the diagnostic yield of a microarray in
approximately 6 to 12%. Thus, this test has a much higher diagnostic yield and any
other genetic test that is routinely performed in individuals with nonspecific
developmental disabilities.

Fragile X: Though the chromosomal microarray analysis is the test with the highest
diagnostic yield in children with developmental disabilities, it will not identify point
mutations or other small mutations that can cause developmental disabilities. For
example, microarray analysis will not identify the trinucleotide repeat expansion that is
seen in individuals with Fragile X. Fragile X is the most common inherited form of
intellectual disability. For these reasons, Fragile X testing must be performed in
addition to chromosomal microarray analysis in individuals with global developmental
delay and intellectual disability with or without an autism spectrum disorder.

Since Fragile X is a relatively common cause of intellectual disability and autism, I

would like to review the features of Fragile X in an effort to exemplify many of the
principles about intellectual disability that we have been discussing. The phenotype of
Fragile X includes both neurologic and somatic features. In boys with Fragile X,
moderate to severe cognitive impairment is universal. In addition, the affected
individual may have features of autism or meet the diagnostic criteria for an autism
spectrum disorder, have ataxia, be hyperactive and/or aggressive and may have a
decline in the intelligence quotient with age. Girls who have unfavorable lyonization (the
X chromosome without the pathologic expansion is preferentially inactivated in the
brain) may manifest a learning disability or cognitive impairment. The degree of
cognitive impairment is likely proportional to the percentage of cells in the brain in which
the pathologic X is active. Due to X inactivation, females with the pathologic expansion
on one of their X chromosomes are typically less severely affected than males, and
many are asymptomatic carriers.

The characteristic somatic features seen in individuals with Fragile X (with the
percentage of prepubertal vs. postpubertal incidences in parentheses) include
prominent ears (78 vs. 66%), a long face (64 vs. 80%), a high-arched palate (51 vs.
63%), hyperextensible joints (81 vs. 60%), flat feet (82 vs. 60%), a heart murmur or click

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(16 vs. 29%), and macroorchidism (54 vs. 92%). Of these somatic features,
macroorchidism is the most common. However, note that it is only present in half of the
boys who are prepubertal. Thus, this feature of Fragile X cannot be reliably used to
determine whether or not to perform genetic testing for this syndrome.

Just as X inactivation in girls accounts for the absence or attenuation of cognitive

impairment in girls with Fragile X compared to boys, the somatic features may also be
absent or minimal in affected girls. There is some evidence that the severity of the
cognitive impairment is correlated with the severity of dysmorphic features. However, I
do not use my findings on the dysmorphic examination to guide whether I perform
testing for Fragile X. Since there are no pathognomonic features of Fragile X, I perform
Fragile X testing in all boys and girls with global development delay and intellectual
disability with or without an autism spectrum disorder.

Autism Spectrum Disorders (ASD)

Autism spectrum disorders are classically diagnosed based on dysfunction in
two areas: 1) impaired social communication and social interactions, and 2)
restricted, repetitive activities or interests. ASD is very common. An autism
spectrum disorder affects approximately 1% of children. Of those individuals with an
autism disorder approximately 50 to 75% have intellectual disability, and many also
have sensory sensitivities and/or incoordination.

Impaired communication skills in a child or adult with ASD include deficits of social-
emotional reciprocity, deficits of nonverbal communication, and deficits in developing,
maintaining, and understanding relationships. Deficits of social-emotional reciprocity
includes shared lack of protodeclarative pointing, lack of social reciprocity (showing
empathy or sharing excitement), and lack of joint attention (showing or handing a toy to
a parent or the examiner to share the experience of enjoying the toy). Deficits of
nonverbal communication include lack of sustained eye contact or no eye contact,
inability to understand body language or intonation and nuances of speech, inability to
use gestures, and inability to recognize facial expressions. Deficits in developing,
maintaining, and understanding relationships include playing alone for hours instead of
playing with other children, not participating in imaginative play, having an absence of
the to-and-fro pattern of normal conversation, and not making or being interested in
having friends. Examples of these communication impairments will be shown in class.

The second category of impairment in ASD is repetitive or restricted behaviors.

Repetitive behaviors may be manifested as a stereotypy, a semivoluntional repetitive
movement. Examples of stereotypies include hand flapping and rocking. Children and
adults without ASD or a different developmental disability may also manifests
stereotypies (twirling a pen while studying, twirling hair while reading, bouncing a leg
while concentrating), but stereotypies in individuals with ASD are typically more
prominent than in children with ASD. Children with autism may also have self-injurious
behaviors, like head banging. Self-injurious behaviors are more common in individuals
with comorbid intellectual disability. Children with autism also demonstrate echolalia in

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which they repeat what they heard but do not appear to understand the content of what
they are saying.

Children with ASD may also manifest unusual play with toys, such as spinning the tires
of a car over and over instead of rolling the car on the floor. Alternatively, they may
have an emotional attachment to hard objects like a pen or cup instead of a blanket or
stuffed animal. Older children with ASD may perseverate on topics or ideas, such as
space exploration, dinosaurs, and geology. Though they may have an extensive
knowledge of these topics or ideas, they frequently will only discuss these topics, avoid
talking about any other topic, and do not appreciate that this is socially inappropriate.
Also, the content of their interests may seem misplaced, as in the child who is
fascinated with train schedules instead of trains themselves. Many children with ASD
have obsessive-compulsive traits, like washing their hands or a having a need for a
strict morning or bedtime routine. Examples of these communication impairments will
be shown in class.

In addition, 25-30% of individuals with ASD have experienced regression in their

speech, social skills and gestures at 15-18 months of age. The cause for this
regression at this age in individuals with ASD is unknown.

There are several points of overlap between the management of children with ASD and
the management of children with intellectual disability. First, just as children are
monitored for language delays and motor delays during the well child visits, children
should also be observed for manifestations of ASD during the well child visit. If there
are concerns based on the clinician’s observations or if the family reports concerns
about the child’s social and adaptive milestones, additional screening should be
performed (such as the MCHAT). If concerns for as ASD persist, then the child should
be referred to a child development center for evaluation. This evaluation will include a
comprehensive history and physical examination. Genetic testing is usually also
recommended, including chromosomal microarray analysis, karyotype analysis if the
microarray is normal, Fragile X testing (if the patient has ID), and possibly testing for
other genetic and metabolic conditions based on the medical history and
dysmorphology examination. Psychology testing is usually performed to confirm the
diagnosis and to quantify the child’s cognitive abilities. Finally, if the child has speech
delay, audiology testing and an evaluation by a speech and language pathologist are
indicated.

Comorbid conditions that are common in individuals with ASD include sleep problems,
epilepsy, gastrointestinal problems (constipation, diarrhea, or both), and behavior and
psychiatric problems. Thus, clinicians should inquiry about these potential comorbid
problems and initiation of treatment or referral to a specialist, as indicated. Like children
with global developmental delay or intellectual disability, children with ASD also qualify
for educational services through the Early Intervention Services (younger than 3 years
of age) or the special education services through the local school district (older than 3
years of age). Finally, for children with ASD who have normal intellect or mild
intellectual disability and who do not have severe behavior problems, Applied Behavior

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Analysis (ABA) therapy (discrete behavior training) has been shown to be beneficial.
ABA therapy is the only treatment for ASD that has been unequivocally proven to be
beneficial, but it frequently requires 10-15 or more hours of therapy time each week.

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