CLIPP Case 28 (18-month-old with developmental delay) and Case 29 (Infant with hypotonia)

The incidence of spastic diplegia is greatly increased in what patients

premature infants

What is an example of when greater than three-generation family history is warranted?

If a familial chromosome translocation is identified and additional relatives might be "at risk"

According to a survey conducted in 2004, what percent of primary care providers routinely screened for autism spectrum disorder?

8%

To improve rates of detection, the AAP now recommends developmental screening using a validated screening tool for all children at a minimum what ages?

9, 18 and 30 months.

Major cerebral palsy associated pathologies other than acute intrapartum hypoxia were identified in what percent of cases?

98%

Spastic quadiplegia is associated with what findings?

Spasticity, clonus, and exaggerated tendon jerks throughout their bodies. Imaging would show global brain abnormalities.

Athetoid cerebral palsy involves what deficits?

Entire body deficits, It is often caused by perinatal asphyxia and kernicterus, both of which damage the basal ganglia, cerebellum, and/or thalamus.

To calculate corrected age

Subtract gestational weeks of a premature infant from the average gestational period of 40 weeks. Subtract the result from the chronological age to obtain the "corrected age."

Which of the following evaluations will infants and children with Down syndrome need during the first 10 years of life?

1. Repeat thyroid testing 2. Vision screening 3. Hearing screening 4. Complete blood count in first month 5. Pediatric cardiology referral 6. Annual hemoglobin and hematocrit, 7. Early intervention

Risk Factors for Developmental Delay?

1. Bronchopulmonary dysplasia (BPD) 2. Retinopathy of prematurity (ROP) 3. Hyperbilirubinemia 4. Periventricular leukomalacia (PVL)

Developmental Monitoring involves a careful review of progress in each of several different domains. The most widely used frameworks for developmental monitoring address most or all of the following domains?

1. Gross motor 2. Fine motor 3. Communication (sometimes broken down into receptive and expressive language) 4. Personal-social 5.Problem-solving (also called self-help or adaptive in some frameworks)

Diagnostic evaluation of a patient with the potential diagnosis of cerebral palsy.

1. H&P 2. Screening 3. EEG 4. Neuroimaging 5. Metabolic and genetic testing 6. Developmental testing

Common features of more than 50% of infants with Down syndrome include:

1. Upslanting palpebral fissures 2. Small ears [usually less than 34 mm at maximum dimension in a term infant] 3. Flattened midface 4. Epicanthal folds 5. Redundant skin on back of neck (nuchal skin) 6. Hypotonia [most consistent finding in infants with Down syndrome]

There are many ways to present medical information to patients. Each of the above approaches represents a different learning style or preference for taking in new information. According to one learning style framework includes what?

1. Visual learners learn best by seeing. 2. Auditory learners prefer to listen and discuss new information verbally. 3. Some learners do best with reading and writing. 4. Kinesthetic or tactile learners prefer hands-on experiences and strategies that tap all five senses. Note its most effective for physicians to take a multimodal approach, combining two or more strategies for sharing information.

Turner syndrome is associated with what physical findings?

1. Webbed neck 2. Low ear placement 3. Edema of the hands and feet 4. Hyperconvex nails, and 5. "Shield" chest, with widely spaced nipples

Physical features of Fragile X syndrome include what?

1. long face with a large mandible 2.large, prominent ears 3. large testicles (after puberty)

The AAP recommends routine screening for autism spectrum disorder in all children at what visits?

18 and 24-month visits

In part due to low screening rates, the mean age of first evaluation of children with autism is when?

48 months, well after symptoms of the disorder present

spastic hemiplegia is associated with what?

A stroke damaging a unilateral upper motor neuron tract—should present with spasticity of the contralateral arm and leg, not the entire body.

Athetoid cerebral palsy

Also know as dyskinetic cerebral palsy [sometimes abbreviated ADCP] is a type of cerebral palsy primarily associated with damage, like other forms of CP, to the basal ganglia in the form of lesions that occur during brain development due to bilirubin encephalopathy and hypoxic-ischemic brain injury.

Use corrected age to plot growth parameters.

According to the U.S. Centers for Disease Control and Prevention (CDC), use of corrected age on growth charts should be discontinued after the child reaches 2 years. Most premature infants have caught up by then, especially in terms of height; some still lag behind their same-age peers in weight.

Retinopathy of prematurity Epidemiology based on weight?

All premature infants, particularly those weighing less than 1500 g are at risk of ROP. Approximately 50% of infants weighing less than 1200 g develop ROP.

Gastroesophageal reflux (GER) and prematurity?

Almost all infants have some degree of GER, Premature infants have a higher incidence due to a physiologic incompetent lower esophageal sphincter, Esophagitis or failure to retain sufficient calories due to vomiting can negatively impact growth, Development usually is not affected.

What are other common karyotypes seen in down syndrome other than the most likely [Trisomy 21]

An unbalanced chromosome translocation resulting in extra chromosome 21 material; and Mosaicism for a trisomy 21 cell line.

Timing of thyroid screening during the first 10 years of Down Syndrome children?

Annual screening due to an increased incidence of hypothyroidism, even if not present at birth

Why would you order echocardiography in a down syndrome patient?

At least 50% of infants with Down syndrome will have normal cardiac anatomy, but cardiac abnormalities are common. Note that finding of a cardiac malformation by echocardiogram does not necessarily confirm the diagnosis of Down syndrome.

Why do you need to carefully take a history and physical examine at every Down syndrome well-child check?

Because of the increased incidence of atlantoaxial instability, which present as symptoms possibly attributable to spinal cord impingement are reported. At least biennially, the importance of cervical spine-positioning precautions for protection of the cervical spine during any anesthetic, surgical, or radiographic procedure should be discussed with parents.

Hemoglobin and hematocrit should be obtained to screen for iron deficiency anemia [due to increased risk for iron deficiency due to lower dietary iron intake than their peers]

Beginning at 1 year of age, and then annually

Hyperbilirubinemia

Bilirubin is a potential neurotoxin, particularly in preterm or critically ill infants. Severe hyperbilirubinemia may lead to kernicterus, which is characterized by abnormal motor development [choreoathetoid cerebral palsy] and sensorineural hearing loss.

Ataxic cerebral palsy should show what on imaging?

Cerebellar abnormalities

Anton is a non-dysmorphic 18-month-old male ex-29-week preemie who exhibits delays in gross motor and language developmental milestones with hypertonicity and hyperreflexia in the lower extremities and a positive Babinski sign. Likely diagnosis?

Cerebral palsy

PVL with cysts (cystic PVL) is highly correlated with what?

Cerebral palsy

Down Syndrome (Trisomy 21) Risk Factors [parents explanation]

Children with Down syndrome can be born to any couple, regardless of their age. The chance of having a child with Down syndrome increases as the mother's age increases (particularly beginning in the mid-30s). The reason for this is unknown.

Prenatal testing for Down Syndrome?

Chromosome analyses of amniotic fluid cells and chorionic villous sampling (CVS) are both direct diagnostic tests for Down syndrome, because the cells that are obtained and analyzed are of fetal origin. Both amniocentesis and CVS do have risks of complications, particularly a slight risk of causing a miscarriage.

Metabolic and genetic testing for Cerebral Palsy?

Considered if the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination.

Children with autism present with what?

Delays in language and social interaction, rather than with motor delays. Motor development is typically normal.

visual, auditory, and sensorimotor function have a major impact on developmental progress, they are not considered what?

Domains of development for the purpose of developmental monitoring.

Down Syndrome (Trisomy 21) pathophysiology [parents explanation]

Down syndrome is caused by the presence of an extra small chromosome (chromosome 21) in each somatic cell.

Differentail diagnosis of hypotonia in a newborn?

Down syndrome, benign neonatal hypotonia, Zellweger syndrome, family resemblance

What type of cerebral palsy is associated with jaundice?

Dyskinetic CP is associated with kernicterus, due to hyperbilirubinemia, as well as findings of basal ganglia pathology on imaging. Patients typically have motor abnormalities throughout the body. Dyskinetic CP is also associated with perinatal asphyxia and can involve the thalamus and cerebellum on imaging.

Spastic diplegia is

Form of cerebral palsy, a non-progressive static encephalopathy characterized by delays in motor development. It may be associated with periventricular white matter abnormalities that are thought to be due to ischemia. These changes can be visualized on MRI. In spastic diplegia, the motor abnormalities are often greater in the legs than in the arms.

What is the most common familial cause of intellectual disability?

Fragile X is an X-linked disease caused by the inheritance of an abnormal number of CGG repeats in the FMR1 gene. NOTE:Trisomy 21 is probably the most common cause of intellectual disability that involves genetic material, but trisomy 21 is usually not familial.

Is benign neonatal hypotonia associated with facial and/or had features?

Generally they not associated with unusual facial or hand features.

Genetic and metabolic disorders may cause what type of delays?

Global delay

Which newborn screening tests is most likely to be abnormal in an infant with Down syndrome?

Hypothyroidism. Before the advent of cytogenetic testing, there was frequently diagnostic confusion between infants with Down syndrome and those with congenital hypothyroidism.

In most pediatric clinical situations, how many generations should a family history cover?

In general, a three-generation (B) family history is obtained and recorded as part of a complete evaluation. One of the benefits of a three-generation pedigree is that it helps exclude consanguinity at the first-cousin level

What is Zellweger syndrome?

Infants with Zellweger syndrome a peroxisomal disorder are generally hypotonic and poorly responsive.

What are the 2 though 4 causes of cerebral palsy by percent risk of each?

Intrauterine growth retardation, 34%; Intrauterine infection , 28%; Perinatal asphyxia, 10%

What are classic findings of Cerebral palsy seen on MRI in the case?

Irregularly shaped ventricles and increased FLAIR signal indicating periventricular leukomalacia. Thinned corpus callosum.

Autism spectrum disorder definition?

Is a developmental disorder that primarily interferes with healthy social interaction?

Why do we refer to pediatric cardiologist in down syndrome children?

It is due to the increased incidence [50%] of structural heart disease in patients with Down syndrome and the difficulty of auscultating some of these cardiac defects

Mosaicism in Trisomy 21

It is virtually impossible to absolutely exclude mosaicism, because only a small number of cells are actually examined as part of the chromosome analysis, and these are usually all from the same cell type. However, results of +21 in all 20 lymphocytes imply that the baby is probably not mosaic.

Why is kernicterus rare

Largely because of advances in preventive management.

Premature infants are defined as?

Less than 37 weeks?

Turner syndrome is associated with what in utero?

Lymphedema

What is the diagnostic testing standard of care for Trisomy 21

Lymphocyte karyotype remains the standard for the laboratory diagnosis of Down syndrome. NOTE: Fluorescence in-situ hybridization ["FISH"] studies of uncultured cells have not replaced lymphocyte karyotype as the diagnostic study of choice.

Neuroimaging is recommended to both establish an etiology and for prognostic purposes and what is the preferred imaging tests?

MRI is preferred to CT scan

Prenatal screening for Down Syndrome?

Maternal serum screening and fetal ultrasound can potentially screen for Down syndrome [and other chromosomal abnormalities]; that is, they can provide information about the risk of having an affected fetus, but cannot definitively diagnose for a specific condition.

Bronchopulmonary dysplasia or chronic lung disease

May cause poor growth in part due to increased caloric requirements, repeated pulmonary infections or congestive heart failure. Development in these infants may be delayed because of prolonged or repeated hospitalization due to illness, underlying neurological disease, or both.

Does having had previous pregnancies significantly change the maternal age-related risk of having a child with Down syndrome?

No

Is Consanguinity a risk factor for down syndrome?

No

15 year old that is unable to draw/scribble or grasp markers. He can say one syllable words "ma" and "da" but his words are unintelligible. Is this appropriate?

No, a 15-month-old child should be able to scribble, use a cup, and/or stack 2 blocks. His word count should be three to six words at this stage of development.

Is paternal age as important as maternal age as a risk factor for Down syndrome?

No, there is no strong paternal age effect in down syndrome

What is the most common known risk factor for cerebral palsy?

Prematurity 78% risk

Retinopathy of prematurity is characterized by what?

ROP is characterized by extraretinal fibrovascular proliferation and, in severe cases, may cause retinal detachment and blindness. Development in children with ROP may be delayed depending on the degree of visual impairment.

What separates a patient with down syndrome from a normal variation?

Remember that almost all of the findings in can be seen individually in people who do not have Down syndrome. It is the combination of findings that separates a syndrome from normal variation.

Periventricular leukomalacia

Result of damage to the white matter surrounding the ventricles in the brain as a result of hypoxia, ischemia, and inflammation. It is correlated with intraventricular hemorrhage it is likely that damage to the white matter is actually more widespread, but not easily visualized using current clinical imaging techniques.

Screening for cerebral palsy patients?

Screening for developmental delays, ophthalmologic abnormalities, hearing impairment, speech and language disorders, and disorders of oral-motor function are warranted as part of the initial assessment because these problems are commonly associated with CP

Autism spectrum disorders primarily interfere with what?

Social interactions

Spastic diplegia is associated with what?

Spastic diplegia is classically associated with premature birth and specific MRI findings of periventricular white matter abnormalities. Patients present with motor involvement that is more prominent in the legs than the arms.

Advantages of Chromosomal Studies

The "yield" on chromosome studies depends on the clinical indication, but even in patients with multiple malformations that do not fit a recognizable chromosomal syndrome there is justification for doing chromosome studies.

Screening tools for autism

The Modified Checklist for Autism in Toddlers (M-CHAT) is a parent-completed questionnaire that is validated as a screening tool to identify children between 16 and 30 months of age who are risk for autism spectrum disorders.

What topics should be mentioned in discussing the diagnosis of Down syndrome with a family?

The cause, The relationship between the chromosome abnormality and the clinical findings, Common complications and how we will screen, 'Anticipatory guidance" in caring for there child, Implications of the diagnosis for the parents of the child, as well as for other relatives, unavailability of prenatal diagnosis

Cerebral palsy definition

The diagnosis of cerebral palsy (CP) represents a heterogeneous group of non-progressive disorders, characterized by motor and postural dysfunction. These conditions, which range in severity, are due to abnormalities of the developing brain resulting from a variety of causes.

Cerebral palsy types?

The different types of cerebral palsy have been grouped together because they all involve motor abnormalities and are treated somewhat similarly. Spastic diplegia is characterized by increased tone and spasticity predominantly involving the lower extremities.

Spastic diplegia effect what part of the body most?

The motor abnormalities are often greater in the legs than in the arms.

Autism spectrum disorder prevalence?

The overall prevalence is 6 per 1000, or 0.6%

Cerebral palsy prevalence?

The overall prevalence of cerebral palsy in western countries is 2/1000

Down Syndrome [Trisomy 21] Epidemiology [parents explanation]

The syndrome is present in about 1 in 700 births in the U.S.

If risk of having a baby with Down Syndrome per pregnancy is higher for women age 35 years and older at delivery why are most infants with Down syndrome born to women of younger then 35 years of age.

This is because there are many more total pregnancies in these younger women.

What can cause a temporary loss of developmental achievements?

Time of stress

what is the most likely chromosome finding in down syndrome?

Trisomy 21 [47, XY,+21 in boys] and the most common and most likely, regardless of the mother's age.

Turner syndrome physical findings?

Turner syndrome [45, X]

Testing Deep Tendon Reflex?

Use your finger to tap the tendons. Use the same method as when you percuss. Note vigorousness of response (if you repeat this maneuver on all the toddlers you see, you'll get a sense of 2+ vs. 4+ reflexes.) Pay special attention to asymmetry here as well and note any correlation with asymmetry of tone or muscle bulk.

Muscle strength testing in children?

Watch the child for any obvious weakness as he plays. Also see how much the child resists your physical-exam maneuvers (e.g., kicking). Look carefully for asymmetry of muscle bulk!

Testing cerebellar function in children?

Watch the child play with toys in the room. Is his balance normal. Does he have smooth, coordinated movements. Look carefully for asymmetry.

The likelihood of finding a translocation increases with what?

[CHECK THIS] In infants born to younger mothers, but trisomy is still most likely, regardless of the parental age.

Maternal serum screening for Down Syndrome measures what?

may include alphafetoprotein, human chorionic gonadotropin, estriol, PAPP-A, and/or inhibin. This is a rapidly developing area, and newer tests and combinations of tests may be available. These tests are not specific for Down syndrome, however.

Neimann-Pick disease

neurodegenerative disease that can present in children between the ages of 6 months and 2 years. It causes global delays as well as regression of milestones. Other signs and symptoms include hepatosplenomegaly, interstitial lung disease, and a macular cherry red spot.

family history of infant deaths raises the possibility of what?

chromosomal/genetic abnormality or metabolic disorder

Which of the following is seen at a higher rate in down syndrome? Downslanting palpebral fissures, ocular hypotelorism , cleft lip or palate and a bulbous nose

cleft lip or palate, but note that while cleft lip or palate may be seen in Down syndrome at a rate higher than that of the general population, it is not a common finding.are not features of Down syndrome.

Who are patients that are good candidates for chromosome studies?

clinical features of a known chromosome disorder, unrecognized malformation syndrome, known genetic condition but with additional or more severe findings, mental retardation and other unusual findings [including short stature], Born stillborn with multiple malformations, features of a chromosome breakage syndrome, tumors, Multiple pregnancy losses, family history of chromosome rearrangement.

cerebral palsy often presents with what?

defects in motor development and are often found to have abnormal neuromuscular exams, including increased tone and reflexes. Other areas of development are less consistently impacted.

Cerebral palsy is characterized by

motor dysfunction, with variable impact on other domains

EEG is recommended when there are CP with features suggestive of what?

epilepsy

Complete blood count in first month screening during the first 10 years of Down Syndrome children?

first month to assess for leukemoid reactions, or transient myeloproliferative disorders (TMD)

Some chromosome abnormalities actually are submicroscopic deletions that may not be obvious on a routine cytogenetic study, but may require what type of specific testing?

fluorescence in-situ hybridization (FISH) probes for detection. Note a newer test for detecting submicroscopic chromosome deletions or duplications is array comparative genomic hybridization.

What does a detailed ultrasound look for when screening for Down Syndrome?

looking at nuchal skin thickness, nasal bone ossification and other growth parameters, has been used to identify fetuses at increased risk for having Down syndrome. Ultrasound may be used in combination with maternal age and analyte measurement to better refine the risk that a fetus is affected with Down syndrome or another common chromosomal abnormality.

What is the interesting trend see with hypothyroidism in Down syndrome?

the incidence of hypothyroidism is increased in infants with Down syndrome [both congenital hypothyroidism and also hypothyroidism that develops later in childhood]