Behavior and development

1

What are the characteristics of attention-deficit/hyperactivity disorder (ADHD)?

ADHD is a chronic neurodevelopmental and behavioral disorder, considered to have neurobiologic origins, that is diagnosed on the basis of the number, severity, and duration of three clusters of behavioral problems: inattention , hyperactivity , and impulsivity . According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), symptoms of inattention, hyperactivity, and impulsivity must have lasted for more than 6 months and be inconsistent with the child’s developmental level. These symptoms have to involve more than one setting and result in significant functional impairment at home, school, or in social settings. Some symptoms must have begun before the age of 13 years.

2

How common is ADHD?

Community prevalence studies indicate that 4% to 12% of school-age children are affected by ADHD. It is the most common neurodevelopmental disorder in the United States.

3

Are boys or girls more likely to be diagnosed with ADHD?

Males are three to four times more frequently diagnosed with ADHD. Their symptoms tend to be more disruptive, particularly with hyperactivity, whereas girls present more commonly with problems of attention.

4

What is the cause of ADHD?

The pathogenesis remains unknown. Because of differences noted in structural and functional brain imaging between children with and without ADHD, as well as the positive therapeutic response to medications with noradrenergic activity, a primary role appears to be an imbalance of metabolism of neurotransmitters, particularly catecholamines, in the cerebral cortex.

5

Is there a genetic predisposition to ADHD?

ADHD has a high rate of heritability . In studies of identical twins raised apart, if one twin has ADHD, the other has up to a 75% likelihood of being diagnosed with ADHD. In nonidentical twin studies, the concordance rate is as high as 33%. Studies of siblings of patients with ADHD indicate a 20% to 30% likelihood. About 25% of children with ADHD have at least one parent with symptoms or a diagnosis of ADHD. Genome-wide linkage and fine mapping studies support the linkage between ADHD and various chromosomal bands and candidate genes. Genes that regulate dopaminergic pathways are suspected to be involved in ADHD’s pathogenesis. However, gene variants suspected in ADHD are only weakly predictive and currently have only limited clinical value.

6

Is there a definitive diagnostic test for ADHD?

No. Diagnosis requires evidence of characteristic symptoms occurring in high frequency over an extended period. This information, which is ideally obtained from at least two settings or sources (e.g., school and home), can be garnered from observation, narrative histories, and the use of various standardized rating scales. The use of validated ADHD questionnaires is recommended by the American Academy of Pediatrics (AAP), but these rating scales are underutilized in diagnostic evaluation (only about 50% of the time) and in therapeutic monitoring after treatment (10% or less of the time).

7

How should ADHD be treated?

A multimodal approach is recommended, which may include psychotropic medication, behavioral therapies, family education and counseling, and educational interventions.

8

What are the best medications for treating ADHD?

Stimulant medications (methylphenidate, mixed amphetamine salts, and dextroamphetamine) are typically first-line treatments. Randomized, controlled trials support their benefits, usually by demonstrating an improvement of core ADHD symptoms in 70% to 80% of children. Of the 20% to 30% of nonresponders to one medication, about one-half will respond to the other stimulant. Other medications used to treat ADHD include atomoxetine (a norepinephrine-reuptake inhibitor), central α-adrenergic agonists (e.g., clonidine), tricyclic antidepressants, and atypical antidepressants (e.g., bupropion). There is concern about the possible overuse of stimulants in children of all ages.

9

Is a positive response to stimulant medication diagnostic of ADHD?

A positive response is not diagnostic because (1) children without symptoms of ADHD given stimulants demonstrate positive responses in sustained and focused attention and (2) observer bias (i.e., parent or teacher) can be considerable. Thus many experts recommend a placebo-controlled trial when stimulant medication is used.

10

Is an electrocardiogram (ECG) required before beginning patients on stimulant medication for ADHD?

This is controversial. Case reports of sudden death among pediatric patients treated with ADHD medications prompted the U.S. Food and Drug Administration (FDA) in 2005 to 2006 to issue warnings on stimulant medication use in ADHD patients. The American Heart Association listed the indication for an ECG in this setting as class II, indicating uncertainty as to its need or lack of need. Large studies subsequently did not demonstrate an increased risk compared with the background rate of sudden death. Many pediatric cardiologists do not recommend an ECG because the ECG as a screening test has low positive and negative predictive values in this low-risk population.

11

How young is “too young” to diagnose ADHD and prescribe stimulant medications?

The AAP recommends an initial evaluation for ADHD for any child as young as age 4 years with academic or behavioral problems and symptoms of inattention, hyperactivity, or impulsivity. Behavior therapy is advised as the first line of treatment, but methylphenidate may be prescribed if behavior therapy results in no significant improvement and moderate to severe disturbance is occurring in the child’s function. Treatment of preschool children, however, is controversial.

12

What are the risks for adolescents with ADHD?

Risks for adolescents involve increased high-risk behaviors , including higher rates of sexually transmitted infections and pregnancies, and increased school problems , including higher rates of grade failure, dropping out, and expulsion. Untreated ADHD has also been found to be a significant risk factor for substance abuse and for automobile accidents.

13

Does sugar or food additives make children hyperactive?

Although it would be gratifying if complex behavioral problems could be attributable solely or in large measure to dietary causes, the majority of controlled studies have failed to demonstrate any significant exacerbations of symptoms from the intake of sucrose or aspartame.

14

Are nonpharmacologic therapies beneficial for ADHD?

These can range from highly structured behavioral interventions to complementary medicines. Many are tried by frustrated parents (often unbeknownst to the primary care provider), such as neurofeedback, megadose vitamin therapy, herbals, and dietary modifications. However, randomized controlled trials are few and, when done, typically demonstrate no benefit.

15

Do children with ADHD become teenagers and adults with ADHD?

Ongoing observations of children initially diagnosed with ADHD note that 70% to 80% will continue to have symptoms present during adolescence and up to 60% will show symptoms as adults. Of the features of ADHD, hyperactivity is the symptom most likely to be outgrown. Inattention, distractibility, and failure to finish things are more likely to persist. Adolescents and adults also have continued problems with anxiety and depression, as well as with tobacco and substance abuse. Motor vehicle infractions, employment difficulties, and intimate relationships have also been described as problematic for adults. Children and adolescents with severe symptoms, mental health problems in parents, and childhood comorbidities (such as conduct disorder or depression) are at the highest risk for severe problems as adults.

16

What is the DSM-5?

The DSM is the Diagnostic and Statistical Manual of Mental Disorders , which is published by the American Psychiatric Association on a periodic basis to diagnose and classify mental and behavioral disorders. Criteria for diagnoses are commonly changed to improve diagnostic accuracy based on new research and ongoing psychiatric practice, but classifications can be controversial. The latest version, DSM-5, was released in May 2013. It replaced the DSM-4, which had been introduced in 1994 and had undergone a number of revisions.

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How did classifications change for disorders of autism in the DSM-5?

Previously, autism spectrum disorders (ASDs) were classified into groups including Asperger syndrome, pervasive developmental disorder, not otherwise specified (PDD-NOS), childhood disintegrative disorder (with developmental deterioration after 24 months of age), and autistic disorder. The DSM-5 eliminated these separate subcategories and folded all individual groups into the broader term of ASD with two essential features (see question 19). Clinicians rate the severity of autistic features to classify patients with severity dependent on the extent of support required to compensate for problems with social communication/interaction and repetitive/restrictive behaviors.

18

How is the diagnosis of autism established?

Behavioral, historical, and parental reports are assessed, commonly by a multidisciplinary team, through the use of a number of possible diagnostic tools, including the Autism Behavior Checklist (ABC) and the Autism Diagnostic Observation Schedule (ADOS). These tools can include questionnaires, checklists, and direct-observation assessments of a child’s social interaction, communication, and imaginative play.

19

What are the two essential features of autism?

• Impaired social interaction and social communication (e.g., extreme aloneness, failure to make eye contact, deficit in nonverbal communicative behaviors for social interaction, deficits in maintaining and understanding relationships)

• Restricted and repetitive patterns of behavior (e.g., insistence on sameness or inflexible adherence to routines, stereotyped or repetitive responses to objects, narrow range of interests, hyperreactivity to sensory input, unusual interest in sensory aspects of the environment)

20

Which behaviors of children should arouse suspicion of possible autism?

• Avoidance of eye contact during infancy (“gaze aversion”)

• Relating to only part of a person’s body (e.g., the lap) rather than to the whole person

• Failure to acquire speech or speech acquisition in an unusual manner (e.g., echolalia [repeating another person’s speech])

• Failure to respond to name when called

• Spending long periods in repetitive activities and fascination with movement (e.g., spinning records, dripping water)

• Failure to look in the same direction when directed by an adult (“gaze monitoring”)

• Absence of pointing to show or request something (“protodeclarative pointing”)

• Excessively lining up toys or other objects

• Limited pretend or symbolic play

21

When should screening be done for autism?

The AAP recommends that all children receive autism-specific screening at 18 and 24 months and whenever there is a concern for autism. Younger siblings of patients with autism have a 10- to 20-fold increased risk. Problems with preverbal gestural language and deficits in social skills are present in most children by 18 months of age. Early recognition of autism can lead to earlier intervention, which can improve outcomes markedly. A 20-question M-CHAT-R/F (Modified Checklist for Autism in Toddlers, Revised with Follow-up) is the most commonly used screening questionnaire for children ages 18 to 30 months, although accuracy may be only low to moderate in younger or low-risk children. Other screening tools are available for children younger and older than this age range.

22

What studies should be considered in the evaluation of a child with suspected autism?

• Hearing screening

• Metabolic screening: Urine for organic acids, serum for lactate, amino acids, ammonia, and very long-chain fatty acids (if there is developmental regression, intellectual disability, dysmorphic features, hypotonia, vomiting or dehydration, feeding intolerance, early-onset seizures, or episodic vomiting)

• Karyotype, chromosomal microarray analysis, other genetic testing (if there are dysmorphic features or intellectual disability; more than two dozen genetic syndromes are associated with autism)

• DNA fragile X analysis (if there is intellectual disability or phenotype of long, thin face and prominent ears)

• Electroencephalogram (especially if history of seizures, staring spells, or regression of milestones)

• Neuroimaging with magnetic resonance imaging (MRI) (especially if abnormal head shape or circumference, focal neurologic abnormalities, or seizures)

• Lead level (if history of pica)

23

What accounts for the apparent increase in autism in the United States?

Centers for Disease Control and Prevention (CDC) data indicated a 2014 prevalence rate of ASDs of 1 in 59 (1 in 37 boys, 1 in 151 girls) for children aged 8 years, which was a 13% increase from 2010 estimates of 1 in 68. In 2000, the CDC estimate was a prevalence rate of 1 in 150. Although some experts believe the condition per se is truly increasing in prevalence, other reasons may include diagnostic substitution (which assumes children were previously characterized as developmentally delayed rather than having ASD), broadening of the definition of ASD, and better screening and ascertainment. The largest increase in diagnosed cases has occurred among higher-functioning patients with less severe disease and in black and Hispanic populations.

24

Do vaccines cause autism?

Many claims have been made regarding possible environmental triggers for autism, including vaccines, particularly measles-mumps-rubella (MMR), and vaccine components, primarily thimerosal (a mercury-containing compound used as a preservative in some vaccines). The Institute of Medicine and numerous studies have found no links between the use of thimerosal or MMR vaccine as a cause of autism.

25

Does early intervention and/or therapy improve the outcome in children with autism?

In general, earlier diagnosis and involvement of therapies for children with autism do appear to improve outcomes, such as a decreased need for special education in later years and an increase in the chance for independence as an adult. Certain subsets of children with autism, such as those with no coexisting cognitive deficits, will fare better. Additionally, earlier recognition and intervention may assist families in understanding and coping with potentially challenging medical comorbidities and social and behavioral issues.

26

What are the most common types of behavior problems in children?

• Problems of daily routine (e.g., food refusal, sleep abnormalities, toilet difficulties)

• Aggressive-resistant behavior (e.g., temper tantrums, aggressiveness with peers)

• Overdependent-withdrawing behavior (e.g., separation upset, fears, shyness)

• Hyperactivity

• Undesirable habits (e.g., thumb-sucking, head banging, nail biting, playing with genitals)

• School problems

27

How much do babies normally cry each day?

In Brazelton’s oft-quoted 1962 study of 80 infants, it was found that at 2 weeks of age, the average crying time was nearly 2 hours per day. This increased to nearly 3 hours per day at 6 weeks and then declined to about 1 hour per day at 12 weeks.

28

What is infantile colic?

Colic is excessive crying or fussiness, which occurs in 5% to 20% of infants depending on the criteria used. For study purposes, it is defined as paroxysms of crying in an otherwise healthy infant for > 3 hours per day on > 3 days per week for > 3 weeks. The typical clinical picture is that of an otherwise healthy and well-fed baby (usually between the ages of 2 weeks and 3 months) who cries intensely and inconsolably for several hours at a time, usually during the late afternoon or evening. Often the infant appears to be in pain and has a slightly distended abdomen, with the legs drawn up; occasional temporary relief occurs if gas is passed.

The symptoms nearly always resolve by the time the infant is 3 to 4 months old, but the problem can have repercussions, including early discontinuation of breastfeeding, multiple formula changes, heightened maternal anxiety and distress, diminished maternal–infant interaction, and increased risk for child abuse.

29

What causes colic?

No precise cause has been identified, and the etiology is likely multifactorial. Theories have involved gastrointestinal dysfunction (e.g., intolerance or allergy to cow milk or soy protein, gastroesophageal reflux, lactose intolerance, immaturity of the gastrointestinal tract), neurologic problems (immaturity of the central nervous system [CNS], neurotransmitter imbalance), hormonal processes (e.g., increased serotonin), difficult infant temperament, and interaction problems between the infant and the caregiver (e.g., misinterpreted infant cues, transfer of parental anxiety).

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Are there any treatments that are useful for colic?

As is the case for most self-resolving conditions without a known cause, counseling is the most effective treatment. However, multiple interventions with minimal effectiveness are often tried, and these can include elimination of cow milk from the breastfeeding mother’s diet, formula changes (to soy or to protein hydrolysates), or a trial of herbal tea or simethicone to decrease intestinal gas. Probiotics have been studied as possible remedies, but clinical results are mixed. Medications such as antispasmodics are not recommended because of the risk for side effects. Other sensory modifiers (e.g., car rides, massage, swaddling) are also attempted to provide some course of action until the expected 3- to 4-month resolution.

31

What evaluations should be done for the excessively crying infant?

The infant with acute excessive crying (interpreted by caretakers as differing in quality and persisting beyond a reasonable time, generally 1 to 2 hours, without adequate explanation) can be a taxing problem for pediatricians and emergency room physicians. The differential diagnosis is broad, but infantile colic remains the most common diagnosis (and a diagnosis of exclusion). History and physical examination make the diagnosis in most infants. However, other tests to consider include stool for occult blood (possible intussusception), fluorescein testing of both eyes (possible corneal abrasion), urinalysis and urine culture (possible urinary tract infection), pulse oximetry (hypoxia from cardiac causes may manifest as increased irritability), and electrolytes and blood glucose (possible endocrine or metabolic disturbance).

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How should children be punished?

The goal of punishment should be to teach children that a specific behavior was wrong and to discourage the behavior in the future. To meet this goal, punishment should be consistent and relatively brief. It should be carried out in a calm manner as soon as possible after the infraction. Time-out from ongoing activity and removal of privileges are two punishment techniques that can be used. The use of corporal punishment is controversial. Although spanking and other physical forms of punishment are widely practiced, most developmental authorities argue against their use because they do not foster the internalization of rules of behavior and may legitimize violence.

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How valid is the proverb “spare the rod and spoil the child” as a defense for corporal punishment?

The actual biblical proverb (Proverbs 13:24) reads, “He who spares the rod hates his son, but he who loves him is careful to discipline him.” Although the proverb has often been used as a justification for spanking, in actuality it does not refer to specific discipline strategies, but rather to the need for love and discipline. In addition, the rod may refer to the shepherd’s staff, which was used to guide—rather than hit—sheep.

34

Is physical injury a concern in children with head banging?

Head banging, which is a common problem that occurs in 5% to 15% of normal children, rarely results in physical injury. When injury does occur, it is usually in children with autism or other developmental disabilities. Normal children often show signs of bliss as they bang away, and the activity usually resolves by the time the child is 4 years old. (It may resume spontaneously during pediatric board examinations.)

35

What is the difference between a “blue” breath-holding spell and a “white” breath-holding spell?

Both are nonepileptic, paroxysmal syncopal attacks with involuntary cessation of breathing that occur in up to 4% of children between the ages of 6 months and 4 years. Eighty percent to 90% occur before 18 months of age.

• “Blue” or cyanotic spell : More common. Vigorous crying provoked by physical or emotional upset leads to apnea at the end of expiration. This is followed by cyanosis, opisthotonus, rigidity, and, ultimately, loss of tone. Brief convulsive jerking may occur. The episode lasts from 10 to 60 seconds. A short period of sleepiness may ensue.

• “White” or pallid spell: More commonly precipitated by an unexpected event that frightens the child. Crying is limited or absent. Breath holding and loss of consciousness occur simultaneously. On testing, children prone to these spells demonstrate increased responsiveness to vagal maneuvers. This parasympathetic hypersensitivity may cause cardiac slowing, diminished cardiac output, and diminished arterial pressure, which result in a pale appearance.

36

When should a diagnosis of seizure disorder be considered rather than a breath-holding spell?

• Precipitating event is minor or nonexistent

• History of no or minimal crying or breath holding

• Episode lasts > 1 minute

• Period of postepisode sleepiness lasts > 10 minutes

• Convulsive component of episode is prominent and occurs before cyanosis

• Occurs in child < 6 months or > 4 years old

• Associated with incontinence

37

Does treatment with iron decrease the frequency of breath-holding spells?

In the 1960s, it was observed that children with breath-holding spells had lower hemoglobin levels than controls. Treatment with iron has decreased the frequency of breath-holding spells in some children, most notably those with iron-deficiency anemia. A complete blood count and ferritin level should be considered as part of the evaluation in patients with breath-holding spells. Interestingly, some of the children whose breath-holding spells respond to iron are not anemic, and the mechanism by which iron decreases breath-holding spells is not known.

38

When does prolonged thumb-sucking warrant intervention?

If frequent thumb-sucking persists in a child who is > 4 to 5 years or in whom permanent teeth have begun to erupt, treatment is usually indicated. Persistent thumb-sucking after the eruption of permanent teeth can lead to malocclusion.

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What treatments are used for thumb-sucking?

Treatment commonly has two components: (1) physical modifications, such as an application of a substance with an unpleasant taste, at frequent intervals (such products are commercially available) and/or use of a thumb splint or glove for nighttime sucking; and (2) behavior modification with positive reinforcement (small rewards) given when a child is observed not sucking his or her thumb. Occlusive dental appliances, which interfere with the seal required for sucking, are generally not needed, but are effective when utilized.

40

When should “toilet training” be started?

When a child has language readiness (use of two-word phrases and two-step commands), understands the cause and effect of toileting , seems to desire independence without worsening oppositional behaviors, and has sufficient motor skills and body awareness , training can be begun. The physical prerequisite of the neurologic maturation of bladder and bowel control usually occurs between 18 and 30 months of age. The child’s emotional readiness is often influenced by his or her temperament, parental attitudes, and parent–child interactions. The “potty chair” is typically introduced when the child is between 2 and 3 years old. In the United States, about one-fourth of children achieve daytime continence by 2 years and 98% by 3 years. There are distinct racial disparities regarding parental beliefs. Black parents believe training should be initiated around 18 months compared with 25 months for white parents. Additionally, initiation of toilet training varies considerably by culture and country.

41

Are girls or boys toilet trained earlier?

On average, girls are toilet trained earlier than boys. With regard to most other developmental milestones during the first years of life, however, there do not appear to be significant sex differences (i.e., in walking or running, sleep patterns, or verbal ability). Girls do show more rapid bone development.

42

Are we toilet training children at an earlier age?

On the contrary, there has been a steady increase in the attainment of bowel and bladder continence from approximately 18 months of age in the 1940s to 24 months in the 1950s to 36 to 39 months in the late 1990s. Reasons are unclear, but later initiation of the process and increased incidences of stool toileting refusal and constipation may explain some of the trend.

43

How many fontanels are present at birth?

Although six fontanels are present at birth (two anterior lateral, two posterior lateral, one anterior, and one posterior), only two (the anterior and posterior fontanels) are usually palpable on physical examination ( Fig. 2.1 ).

44

When does the anterior fontanel close?

On the basis of studies using physical examination, classic teaching indicated between 10 and 14 months. However, computed tomography (CT) scans indicate that closure is quite variable and occurs later than previously thought. Only 16% of anterior fontanels are closed at 10 months, 50% at 16 months, and 88% at 20 months. Thus about 10% of normal infants may not have complete closure until 20 to 24 months of age. Of note, 3% to 5% of normal infants have closure at 5 to 6 months.

45

Which conditions are most commonly associated with premature or delayed closure of the fontanel?

• Premature closure: Microcephaly, high calcium–to–vitamin D ratio in pregnancy, craniosynostosis, hyperthyroidism, or variation of normal

• Delayed closure: Achondroplasia, Down syndrome, increased intracranial pressure, familial macrocephaly, rickets, or variation of normal

46

When is an anterior fontanel too big?

The size of the fontanel can be calculated using the formula: (length + width) / 2, where length equals anterior-posterior dimension and width equals transverse dimension. However, there is wide variability in the normal size range of the anterior fontanel. Mean fontanel size on day 1 of life is 2.1 cm, with an upper limit of normal of 3.6 cm in white infants and 4.7 cm in black infants. These upper limits may be helpful for identifying disorders in which a large fontanel may be a feature (e.g., hypothyroidism, hypophosphatasia, skeletal dysplasias, increased intracranial pressure). Of note is that the posterior fontanel is normally about the size of a fingertip or smaller in 97% of full-term newborns.

47

What are the types of primary craniosynostosis?

Craniosynostosis is the premature fusion of various cranial suture lines that results in the ridging of the sutures, asymmetric growth, and deformity of the skull. Suture lines (with resultant disorders listed in parentheses) include sagittal (scaphocephaly or dolichocephaly); coronal (brachycephaly); unilateral, coronal, or lambdoidal (plagiocephaly); and metopic (trigonocephaly). Multiple fused sutures can result in a high and pointed skull (oxycephaly or acrocephaly) ( Fig. 2.2 ).

48

What is the most common type of primary craniosynostosis?

Sagittal (60%); coronal synostosis accounts for 20% of cases.

49

What causes craniosynostosis?

Most cases of isolated craniosynostosis have no known etiology. Primary craniosynostosis may be observed as part of craniofacial syndromes, including Apert, Crouzon, and Carpenter syndromes. Secondary causes can include abnormalities of calcium and phosphorus metabolism (e.g., hypophosphatasia, rickets), hematologic disorders (e.g., thalassemia), mucopolysaccharidoses, and hyperthyroidism. Inadequate brain growth (e.g., microcephaly) can lead to craniosynostosis.

50

What is positional or deformational plagiocephaly?

Since the implementation of the “back-to-sleep” program by the AAP in 1992 to reduce the risk for sudden infant death syndrome (SIDS), an estimated 13% to 20% of infants develop occipital flattening (posterior or lambdoidal plagiocephaly) due to transient calvarial deformation from prolonged supine sleeping positions. The condition can be prevented by varying the infant’s head position during sleep and feeding and by observing prone positioning (“tummy time)” for at least 5 minutes daily during the first 6 weeks of life. Therapy for severe cases consists of repositioning; physiotherapy; and, rarely, surgery. Helmet therapy, although widely used, has not been shown to be effective in one randomized study.

51

How is positional plagiocephaly differentiated from plagiocephaly caused by craniosynostosis?

Synostotic lambdoidal plagiocephaly is much rarer. It is usually associated with ridging of the involved suture lines, and it causes a different pattern of frontal bossing and ear displacement when the infant’s head is viewed from above ( Fig. 2.3 ).

52

What conditions are associated with skull softening?

• Cleidocranial dysostosis

• Craniotabes

• Lacunar skull (associated with spina bifida and major CNS anomalies)

• Osteogenesis imperfecta

• Multiple wormian bones (associated with hypothyroidism, hypophosphatasia, and chronic hydrocephalus)

• Rickets

53

What is the significance of craniotabes?

In this condition, abnormally soft, thin skull bones buckle under pressure and recoil like a ping-pong ball. It is best elicited on the parietal or frontal bones and is often associated with rickets in infancy. It may also be seen in hypervitaminosis A, syphilis, and hydrocephalus. Craniotabes may be a normal finding during the first 3 months of life.

54

What evaluations should be done in a child with microcephaly?

The extent of evaluation depends on various factors: prenatal versus postnatal acquisition, presence of minor or major anomalies, developmental problems, and neurologic abnormalities. The diagnosis can be as straightforward as a simple familial variant (autosomal dominant) in a child with normal intelligence, or it can range to a variety of conditions associated with abnormal brain growth (e.g., intrauterine infections, heritable syndromes, chromosomal abnormalities). Evaluation may include the following:

• Parental head-size measurements

• Ophthalmologic evaluation (abnormal optic nerve or retinal findings may be found in various syndromes)

• Genetic testing (e.g., karyotype, chromosomal microarray analysis)

• Neuroimaging (cranial MRI or CT to evaluate for structural abnormalities or intracranial calcifications)

• Metabolic screening

• Cultures and serology if suspected intrauterine infection (e.g., cytomegalovirus [CMV], Zika virus)

55

What are the three main general causes of macrocephaly?

• Increased intracranial pressure: Caused by dilated ventricles (e.g., progressive hydrocephalus of various causes), subdural fluid collections, intracranial tumors, or idiopathic intracranial hypertension (i.e., pseudotumor cerebri)

• Thickened skull: Caused by cranioskeletal dysplasias (e.g., osteopetrosis) and various anemias

• Megalencephaly (enlarged brain): May be familial or syndromic (e.g., Sotos syndrome) or caused by storage diseases, leukodystrophies, or neurocutaneous disorders (e.g., neurofibromatosis)

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