Fran Hickey, MD

Medical Director Sie Center for Down Syndrome Childrens Hospital Colorado, and CU SOM Associate Professor of Pediatrics

Linda Crnic Institute The first global institute to encompass basic research, clinical research and clinical care specifically for people with Down syndrome.

SIE Center Serves as the clinical care center of the Linda Crnic Institute for Down Syndrome.

Global Down Syndrome Foundation The GDSF is a non-profit corporation dedicated to significantly improving the lives of people with Down syndrome by supporting basic research, clinical research and clinical care.

People First Language

Correct name of this diagnosis is Down syndrome. There is no apostrophe

(Down). The s in syndrome is not capitalized (syndrome)

Encourage people to use people-rst language. The person with Down

syndrome, not the Down syndrome person. A person with Down syndrome is not a Downs

It is important to use the correct terminology. A person has Down

syndrome, rather than suers from, is a vicHm of, is diseased with or aicted by

Each person has his/her own unique strengths, capabiliBes and talents. Try

not to use the clichs that are so common when describing an individual with Down syndrome. To assume all people have the same characterisHcs or abiliHes is demeaning. It reinforces the stereotype that all people with Down syndrome are the same and does not encourage opHmizaHon of abiliHes

Child with Down Syndrome

INCIDENCE/PREVALENCE OF DOWN SYNDROME

Incidence
Approximately 100-120 births in Colorado One in 691 births in the US (CDC 2010) EsHmated 300,000 individuals with Down syndrome in the US

Prevalence
Prevalence is rising due to improved medical care Improved school acclimaHon and services that allow

independence or maximize their abiliHes Improved understanding of potenHal for good quality of life and community acceptance/embrace Improved live expectancy to middle and late adulthood into

60s

Young Children with Down Syndrome and Families

Relative strengths
RecepHve vocabulary Social engagement Aect expression Visual memory = early readers

Family strengths

Less incidence of divorce in recent studies Alignment of life values and prioriHes

Health Supervision for Children with Down Syndrome: AAP, August, 2011

These guidelines are designed to assist the pediatrician in caring for the child

with a diagnosis of Down syndrome that has been conrmed by chromosome analysis.

Although a pediatricians iniHal contact with the child is usually during

infancy, occasionally the pregnant woman who has been given a prenatal diagnosis of Down syndrome will be referred for review of the condiHon and the geneHc counseling provided. Therefore, this report oers guidance for this situaHon as well.

Pediatrics 2011;128:393406
Mailed over 300 Copies of Guidelines to PCPs

Down Syndrome Neonatal and Infant 2011 Health Care Guidelines

DOWN SYNDROME 2011 HEALTH CARE GUIDELINES NEONATAL (BIRTH 1 MONTH)

Review parental concerns and chromosomal karyotype Discuss specic ndings /potenHal clinical manifestaHons Refer for geneHc counseling especially if need recurrence rate (TranslocaHon) If vomiHng or absence of stools, check for gastrointesHnal tract blockage (duodenal web or atresia, Hirschsprung disease) Echocardiogram with follow up evaluaHon by a pediatric cardiologist Exam for plethora, saturaHon for hypoxemia Review feeding history to ensure adequate caloric intake and consider feeding study MBS (This guideline was added by AAP 2011)

Feeding Problems: AAP Indications for Obtaining a Swallowing Assessment

Marked hypotonia Slow feeding Choking with feeds Recurrent pneumonia especially RUL or other recurrent or persistent respiratory symptoms Unexplained Failure to Thrive (FTT)

AUDIOLOGY
Pass newborn hearing screen
Rescreen age 6 months Behavioral audiogram (BA) age

Age 1-21 years

BA and Tympanogram every 6

1 year May need sedated BAER if unable to obtain

months unHl bilateral normal hearing established

HEMATOLOGY

Newborn: Obtain CBC

More specic info provided regarding Transient MyeloproliferaHve Disorder (TMD) in guidelines Management of TMD or polycythemia per Hem-Onc specialist guidance Counsel parents of infants with TMD regarding increased risk (20%) for leukemia Need follow up with Pediatric Oncology

ENDOCRINE
Limited changes in AAP 2011 update: Primarily more specic

Newborn
Obtain TSH if Newborn State Screen (NBSS) measures only FT4 Verify NBSS results ConHnue to screen at:
6 and 12 months 18 months Annually from 2 years on with TSH, T4 (sooner if symptoms of

concern for thyroid dysfuncHon)

OPHTHALMOLOGY

Birth: Evaluate for cataracts by looking for red reex

If red reex absent: Need prompt evaluaHon, refer for treatment with ophthalmologist with experHse managing children with DS Unchanged AAP Guideline: Refer all infants with DS for ophthalmology evaluaHon within rst 6 months (3 MONTHS) New AAP Guideline: If nasolacrimal duct obstrucHon present, refer if not resolved by 9-12 months of age (many refer at earlier age) Nystagmus common (20%): Needs follow up with experienced Pediatric Ophthalmologist

Pulmonary Arterial Hypertension (PAH)

Individuals with DS have Increased incidence of PAH Due

to the cardiac and pulmonary co-morbidiHes

In neonates with CHD, the increased prevalence of PAH

can be explained by: Intra-cardiac shunHng Increased pulmonary blood ow PAH Causes of PAH include OSA, hypoxia, polycythemia, and possible geneHc predisposiHon.
Keeping these children appropriately oxygenated is

essenHal for prevenHon and treatment of PAH.

Cua -Pediatr Cardiol (2007)

Early Intervention Services: Entry to Education

Need to set up and document Early IntervenHon contact prior

to DC from the nursery

Ask for Speech involvement to start@ 9 months

Recd Signing Times Video (English and Spanish) from library Need follow up with family at medical and hospital visits: Many at risk families may fall thru the cracks due to the EI system, especially if they move
Therapy services: PT, OT- feeding, S/L, case management, and

nishing with transiHon to preschool

Down Syndrome Childhood 2011 Health Care Guidelines

AIRWAY CONCERNS

First 6 months Discuss with parents symptoms of ObstrucHve Sleep Apnea (OSA) - refer for further evaluaHon if symptoms present Age 1-21 years Discuss symptoms of OSA at each WCC visit: Heavy breathing, snoring, uncommon sleep posiHons, frequent night awakening, dayHme sleepiness, apneic pauses, and behavior problems Note: A paHent with DS who snores has >95% chance of having OSA If symptoms present or abnormal sleep study - refer to physician with experHse in pediatric sleep issues and ENT Discuss obesity as risk factor for OSA Appreciate the eect of al>tude on increasing the incidence of hypoxia

*AAP Recommends a sleep study/PSG for all children with DS by age 4 yr

Atlantoaxial Instability: AAP Screening Recommendations

Major change in AAP guidelines 2011 with

RouBne screening of asymptomaBc individuals is no longer recommended. Why?

1. Plain radiographs dont predict well who is at risk of

developing symptomaHc AAI

2. Normal plain lm does not rule out later risk

ATLANTOAXIAL INSTABILITY
Monitoring for signs
Instruct parents to contact

physician for: Change in gait or use of arms or hands Change in bowel or bladder funcHon Neck pain, sH neck, head Hlt, torHcollis or how child posiHons his/her head Change in general funcHon New weakness

Evaluation of the symptomatic child If symptoms of myelopathy present, obtain plain lateral neck radiograph in neutral posiHon only If normal: may obtain exion/extension radiographs prior to prompt referral If abnormal: no further imaging - refer ASAP to pediatric neurosurgeon or pediatric orthopedic surgeon with experHse in AAI

Atlantoaxial Instability: Advice Regarding Sports Participation

Some sports place children at risk of increased

spinal cord injury and should be avoided, i.e.:

Contact sports, i.e. football and soccer Gymnastics (usually at older ages)

Trampoline should be avoided by all children, with or

without DS, younger than 6 years and by older children unless under direct professional supervision

(AAP POLICY)

Gastrointestinal: Celiac Disease

Each WCC visit review for potenHally related symptoms:
Diarrhea ConsHpaHon - protracted, severe, or unresponsive to

medical management Slow growth Unexplained FTT Anemia Abdominal pain or bloaHng Refractory developmental or behavioral problems If symptoms present, obtain simultaneous: Tissue Transglutaminase IgA (TTG) and QuanHtaHve IgA If labs abnormal: refer for subspecialty assessment If labs normal, but persistent symptoms: rrepeat tesHng Q 3 years

BEHAVIORAL SYMPTOMS

Consider communicaHon, delayed auditory funcHon, school issues If frustraHon think improper school environment Language decit oten > than cogniHve decit ADHD: EvaluaHon by same quesHonnaires as other kids [incidence the same]

ASD regression in DS occurs at an average age of 6 years versus 18 months in the general populaHon AuHsm Treatment Network/AAP recommendaHons Need yearly assessment in WCC of social, language, and socializaHon Consider MCHAT yearly unHl 6 years old Language screening most likely will be delayed

Wandering: Refer to CO Sheris Dept for GPS leg device

DOWN SYNDROME CO-MORBIDITY RULE OF 7: THE FORGOTTEN AND UNDER-DIAGNOSED 7%

Celiac Disease Variable presentaHon; however, may have
neurological and behavioral consequences
Book 01

Seizures - Need to be aware. Since occurs in 2-10%, need to

consider if child has regression in development/behavior
Stern-Goldberg 01

AuHsm Spectrum Disorder/AuHsm - Dicult to diagnose

or recognize this dual diagnosis
Kent 99, Hickey 06

MEDICAL CONCERNS THAT CAN AFFECT BEHAVIOR

If a negaHve change in behavior occurs, consider Thyroid abnormaliHes
Celiac disease Sleep apnea GERD ConsHpaHon

ADOLESCENCE (12-18 YEARS)

Annual:
TSH and T4-Thyroid FuncHon Test Ophthalmological Auditory exam

High incidence of abnormali>es occur in this age group

Monitor for obstrucHve sleep apnea symptoms Pediatric and neurological exam with evaluaHon for spinal cord

compression: deep tendon reexes, gait, and Babinski sign

PreventaHve counseling for adolescents

Use both Down syndrome and typical growth charts

New Clinical Research

NaHonal InsHtutes of Health Studies 2012

MOST RELEVANT CLILCAL STUDIES OUT OF 40 STUDIES [5 PRENATAL TEST STUDIES]

Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed

Standard-Risk Acute Lymphoblastic Leukemia

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed

High-Risk Acute Lymphoblastic Leukemia

Ecacy Assessment of Systematic Treatment With Folinic Acid and Thyroid

Hormone on Psychomotor Development of Down Syndrome Young Children

A Non-Drug Study of The Suitability of Neurocognitive Tests And Functioning

Scales For The Measurement of Cognitive And Functioning Changes in Individuals With Down Syndrome

RESPIRATORY ILLNESS: MAJOR CAUSE OF MORBIDITY AND MORTALITY

Respiratory illnesses are the cause of 80% of admissions to hospital

for children with DS

Ater surgery, children with DS contract respiratory illnesses at a rate of 3x higher

Unknown eect of possible immune decit Consider chronic aspiraHon if recurrent pneumonia - obtain swallow

study

Leading cause of mortality in published studies

McDowell 11

OBSTRUCTIVE SLEEP APNEA (OSA)

Airway obstrucHon leads to chronic hypoxia which can cause

PAH and possible cardiac issues

OSA can also contribute to behavior and learning issues Tonsillectomy and adenoidectomy is oten 1st line of treatment

of OSA

Need follow up sleep study since as many as 25-50% will sHll have

OSA/hypoxemia following T and A, especially at higher alHtudes

Parental history alone does not idenHfy OSA, NEED SLEEP

STUDY

Cardiac-Pulmonary Vascular Issues: Pulmonary Arterial Hypertension (PAH)

Increased incidence of PAH in individuals with DS when

compared to the general populaHon. Due to the cardiac and pulmonary co-morbidiHes faced by individuals with DS, as well as an undened predisposiHon of this populaHon to PAH.

Causes of PAH include OSA, hypoxia, polycythemia, and possible

geneHc predisposiHon.

Keeping these children appropriately oxygenated is integral for

prevenHon and treatment of PAH.

DENTAL ISSUES : Individuals with Down syndrome Have a

Low prevalence of dental caries
RESULTS: Down syndrome children had a higher

caries-free rate (p,0.05) and lower salivary mutans streptococci counts (p,0.03) compared to their siblings. mutans streptococci in the saliva may be one of the factors contributing to the lower caries rate observed in Down syndrome

CONCLUSIONS: In conclusion, the lower number of

Areias 2012

What has happened since we opened Sie Center for Down Syndome ?

SCDS IMPACT ON COMPLIANCE TO AAP/ DOWN SYNDROME GUIDELINES Total paHents=437 Referrals for Guidelines=379
400 350 300 250 200 150 100 50 0 165 126 379 316 244 271

CoordinaHon of Clinical Care

Improving access, coordination and level of care for our patients Multispecialty Clinics DS ENT/sleep clinic DS Pulmonary/sleep clinic Coordination of care with subspecialists Aerodigestive Team at CHC SCDS is #1 referral source Pulmonologists 5 Cardiologists 5 GI 3 ENDO 2 Neonatologists 2 Neurologists 4 Neurosurgeons 2 35

SIE CENTER ENTERS FRONTIER of CLINICAL RESEARCH in DOWN SYNDROME

CLINICAL RESEARCH
Active Comirbs The Sie Center for Down Syndrome Phenotypic Database Population-based study of incidence of autoimmune diseases in children with Down syndrome Pain Medication in Down syndrome during Cardiac Procedure; Pharmacokinetics and Pharmicogenetics Studies awaiting funding A Methyl Donor-Rich Diet to Improve Immune Function and Normalize DNA Methylation in Down syndrome Comirbs in process Outcome Study of children with Infantile Spasms Audiology and ENT Issues in Down Syndrome

AUTOIMMUNE STUDY OF CHILDREN WITH DOWN SYNDROME

Document incidence of autoimmune disorders in

children and young adults with DS

Use this data to improve identication of these

co morbidities
Direct future auto-immune evidence based care of

this population

AUTOIMMUNE STUDY Outcome Measures

Dene the incidence of autoimmune diseases among

children with DS in the large study population

Identify the way children with DS are diagnosed with

autoimmune disorder.
Determine the aect the Sie Center has made on the

individuals with autoimmune disorders

Develop best practices for autoimmune evidence-

based care.

RESPIRATORY ILLNESS: MORBIDITY AND MORTALITY

Respiratory illnesses are the cause of 80% of

admissions to hospital for children with DS Ater surgery, children with DS contract respiratory illnesses at a rate of 3x higher Unknown eect of possible immune decit Consider chronic aspiraHon if recurrent pneumonia - obtain swallow study Leading cause of mortality in published studies

Pulm DS team meeHng regularly:5 Pulm MDs,CNPs,fellows,RN and Sie Center CHC needs to be the na>onal leader in pulmonary/Down syndrome complica>ons leading to protocols and guidelines

AUDIOLOGY : DOWN SYNDROME STUDY

Sie Center: Audio & ENT Database in process of

development Evaluate Data on Hearing tests ENT procedures Guideline compliance Sleep studies

IMMUNE DEFICITS COMMON IN DS

Possible EHologies: Impaired T-cell proliferaHon ReducHons in subpopulaHons of lymphocytes (CD4 T cells) Low plasma level of zinc Lymphocytopenia Reduced anHbody response to immunizaHons

Consider defects of neutrophil chemotaxis Children with chronic cardiac or pulmonary disease: 23-valent pneumococcal polysaccharide vaccine (PPS23) at 2 years or older

study in process to address immune issues with Ben Tycho, FH

NIH Toolbox Assessment of Neurological and Behavioral FuncHon Request for InformaHon (RFI)
Develop measures of cognitive, emotional,

sensory, & motor health & function: 1) Executive Function 2) Processing Speed 3) Learning and Memory 4) Language 5) Attention 6) Working Memory
SCDS recently contacted to be involved

Cardiac / Pulmonary Studies and DB

1 Increased incidence of PAH in individuals with DS when compared to the general population. Due to the cardiac and pulmonary co-morbidities faced by individuals with DS, as well as an undefined genetic predisposition of this population to PAH. 2 The pharmacokinetics of morphine in post-operative cardiac patients with Down Syndrome. Study Improve patient care in CICU This study will lead to future understanding of the pharmacogenomics and pharmokinetics of opiods in DS

1 Drs Ivy ,Adman Team w/ their PAH DB CICU study to improve Pain management 2 Directors CICU and Fellow Dr Goot

OBSTRUCTIVE SLEEP APNEA (OSA)

Airway obstrucHon leads to chronic hypoxia which can cause

PAH and possible cardiac issues OSA can also contribute to behavior and learning issues Tonsillectomy and adenoidectomy is oten 1st line of treatment of OSA
Need follow up sleep study since as many as 25-50% will sHll have

OSA/hypoxemia following T and A, especially at higher alHtudes

Parental history alone does not idenHfy OSA Proposed study by Dr Halbower in DS to follow up on her

recent nding altered brain metabolites in frontal lobes normalize with OSA treatment improved neuropsych tests

DOWN SYNDROME CO-MORBIDITY RULE OF 7: THE FORGOTTEN AND UNDER-DIAGNOSED 7%

Celiac Disease Variable presentaHon; however, may have
neurological and behavioral consequences
Book 01
Dr Liu ;Autoimmune study

Seizures - Need to be aware since occurs in 2-10%, need to

consider if child has regression in development/behavior
Stern-Goldberg 01 from CincinnaH Childrens DB Dr Knupp and Benke-- IS DB

AuHsm Spectrum Disorder/AuHsm - Dicult to diagnose

or recognize this dual diagnosis
Kent 99, Hickey 06 both indicated 7% prevalence rela>onship with CDU,JFK,IDDRC, DS Au>sm Connec>on [new book Woodbine Nov 2012]

Sibling Issues

Cunningham (1998): Manchester Down Syndrome Cohort

Conclusions involving over 100 families followed since 1973:
80% of siblings of children with Down syndrome have

a positive relationship with their parents and sibling

95% are involved with the care of their brother or

sister with Down syndrome

Cuskelly and Gunn (2003)

Data Set -54 siblings of children with Down syndrome: Siblings of children with Down syndrome show more kindness
Siblings participate in more care giving activities Refuted previous literature on gender bias, now rst

born or older sisters do not have a greater share of family responsibilities

 POSITIVE ASPECTS OF DOWN SYNDOME

PERSONALITY :

SOCIAL SKILLS,EMPATHY,IMITATION FAMILY EFFECTS LOWER DIVORCE RATE SIBLINGS MORE RESPONSIBLE,VOLUNTEER
UNIQUE LEARNING STRENGTHS

+VISUAL PROCESSING AND MEMORY;LTM HEART SURGERY OUTCOME IMPROVED IN DS LESS CARDIOVASCULAR DISEASE WITH AGING

 SOLID TUMORS RARELY SEEN IN DS LEUKEMIA [AML] HAS IMPROVED OUTCOME MUCH LOWER INCIDENCE OF SUBSTANCE

ABUSE OR DEATH BY VIOLENCE AND SUICIDE