SMRUTHI SANATH, MDTITLE: MANAGEMENT OF CHILDREN WITH DOWN SYNDROME Target audience: Child Health staff physicians; all pediatric subspecialists; all

courtesy faculty and referring physicians; pediatric residents, medical students and other professional staff at Children’s Hospital.

  Objective: To improve the knowledge of physicians and therefore, their care for

children in rural Missouri, especially those hospitalized or seen at Children’s Hospital.  To offer presentations which are clinically applicable but basic science that applies to the most contemporary treatments or illnesses. 

Speaker Disclosure: Smruthi Sanatha, MD has no relationship with any commercial firm having products related to topics discussed at this conference.  Additionally, as the chairman of this series, Dr. Thomas Loew has no conflict of interest to disclose that would lead to bias in the selection of topics and/or speakers of this series.  Actual disclosure forms are available upon request. The Office of Continuing Education, School of Medicine, University of Missouri is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.        

The Office of Continuing Education, School of Medicine, University of Missouri designates this live educational activity for a maximum of _1_ AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

MANAGEMENT OF

CHILDREN WITH DOWN SYNDROME

Smruthi Sanath, M.D.

Pediatric Resident (PGY-3)

University of Missouri at Columbia

WHAT WILL YOU LEARN FROM THE PRESENTATION ? What is Down syndrome? Characteristics of DS Medical conditions associated with DS Updated health supervision guidelines

from AAP Recognition of co-morbidities that may

be present in DS

WHY IS IT CALLED ? Down syndrome was originally

described in 1866 by John Langdon Down.

Down used the term mongoloid It wasn't until 1959 that a French doctor,

named Jerome Lejeune, discovered it was caused by the inheritance of an extra chromosome 21.

WHAT CAUSES DS?Type Incidence Chromosom

e findingsPhysical features and intellectual disability

Trisomy 21 95% Extra Ch. 21 in every cell

Common form

Translocation 4% Extra part of Ch. 21 attached to another Ch. in every cell

Same as Trisomy 21

Mosaicism 1% Mixture of cells – some with extra Ch. 21 and others normal

Milder physical features and intellectual disability

WHO IS AFFECTED BY DS?In U.S. 1 in 691 Live births. Odds of child with DS at age 35 are 1 in 350. Under age 25, the odds are about 1 in 1200. At age 40, the odds are about 1 in 100. But 80% of births to women <35yrs.

Life Expectancy increasing… Average 58.6yrs 25% live to >62yrs Joyce Greenman of London, turned 87 on March 14,

2012,

WHO HAS INCREASED RISK OF HAVING A BABY WITH DS? Advanced maternal age Having one child with DS previously Carrying the genetic translocation for

DS

CAN DS BE DIAGNOSED PRENATALLY? First trimester

Early screening: maternal age, Nuchal fold, B-hcg, PAPP-A (sensitivity 82-87%)

Second trimester Quadruple screen: maternal age, B-hcg,

unconjugated estriol, AFP, Inhibin (sens 80%)

Integrated screen Combination of both (sens 95%)

Diagnostic CVS, Amniocentesis

NEW TESTING Maternal T21 1 and 2 trimester (high risk patients) 20 ml maternal blood sample Extracts circulating cell-free fetal (“ccff”)

DNA Converts into a genomic DNA library Uses massively parallel genomic

sequencing Detects T21 sensitivity 99.1%,

specificity 99.9% Also detects T18,T13

COUNSELING PARENTS Talking to parents in person about

concerns Social Support Resources -CDC website (birth defects). National center of medical home

initiatives for children with special needs.

National Down syndrome Society (NDSS)

PRENATAL VISIT Prenatal test results -FISH and full

karyotype. Genetics /recurrence rates “Range of variability”, balanced and

positive outcomes Studies/subspecialty consults Available treatments/interventions Options Availability of genetic counseling.

If they want to continue pregnancy, Plan for delivery/neonatal care:

additional subspecialty care. Parent- to- parent contact, local national

groups. Referral to clinical geneticist. Refer to Maternal Fetal Medicine clinic.

Cont.

RESOURCES FOR PRENATAL DIAGNOSIS National Down syndrome

society -www.ndss.org.

DIAGNOSIS Prenatal diagnosis

FISH and full karyotype. obtain copy of the prenatal test results.

Postnatal diagnosis NEW Share as soon as team suspects the

diagnosis.Karyotype only.

FISH rapid (24-48 hrs) but cannot distinguish

among mosaic, translocation and trisomy 21

NEWBORN

WHAT DOES A CHILD WITH DS LOOK LIKE?

Head brachycephaly

Eyes Inner epicanthal folds, Brushfield spots Upward slanting palpebral

fissures Face

Flat appearing, low nasal bridge, small ears Excessive protrusion of tongue

Neck excessive skin at the nape of the

neck,short neck

Fingers and Toes single transverse palmar crease,

and short fifth finger with clinodactyly.

Brachydactyly, wide spacing of 1st and 2nd toes.

CVS VSD and endocardial cushion

defects. CNS

Absent or diminished Moro reflex, Hypotonia and joint hyperflexibility.

Cont.

HEART PROBLEMS 40- Structural problems with

formation of the heart (40-50%) CAVC (45%) VSD (35%) PDA (7%) TOF (4%) Other (1%) Every newborn needs echo Monitor symptoms of CHF

(Feeding, tachypnea, poor weight gain)

Increased risk for pulmonary hypertension.

Refer to cardiologist if echo abnormal

FEEDING PROBLEMS NEW Refer to modified barium

study/MBS. Marked hypotonia. Slow feeding Choking with feeds Unexplained FTT Recurrent pneumonia Recurrent or persistent respiratory sx. To begin with they have anatomical

issues -Oral anomalies, tongue protrusion.

From late infancy, children with DS show a relative increase in Mean weight-for-length and weight-for-height

BMI (weight/stature2) Excessive weight is a problem in

adulthood. One study of individuals with Down

syndrome showed Less than 15% were within desirable with

range 20-30% were overweight, and Almost 50% were obese

GROWTH ISSUES

BREAST FEEDING Breast milk is ideal food for support. Consult lactation support early. Oromotor benefits. Many babies get to breast milk later.

Encourage pumping! Reassure parents. Don’t give up!

GASTROINTESTINAL ISSUESMalformations (12%) Evaluate for duodenal atresia or anorectal

atresia/stenosis by history and exam.GER- If severe or contributing cardiorespiratory

problems or FTT.Constipation- Evaluate for restricted diet/limited fluid

intake, hypotonia, hypothyroidism, GI malformations and Hirschsprung disease (1%).

SENSORY Vision (60%) Cataracts (5%) May progress slowly. Refer to ophthalmologist for

evaluation and treatment.Hearing (75%) Universal Hearing screen

(brainstem auditory evoked potential or otoacoustic emission) at birth.

Follow up completed by 3 months

CARDIORESPIRATORY NEW Car-seat test: For babies with hypotonia or recent cardiac surgery, evaluate in car seat prior to discharge for Apnea Bradycardia O2 desaturation

Stridor Wheezing Noisy breathingIf severe or cardiopulmonary compromise or feeding problems- refer to pulmonologist.

TRANSIENT MYELOPROLIFERATIVE DISEASE

10% of newborns with DS show leukocytosis with presence of blast cells in PBS-Transient Leukemia.

Most children with transient leukemia go into spontaneous remission and recover by 3 months of age. Of those who recover 20% -acute megakaryocytic leukemia (AML )in 4 yrs of age.

Follow up recommended Q 3 months for PBS. Cure rate is more than 80%. If TMD, counsel parents re: risk of leukemia & signs Easy bruising, petechiae, onset of lethargy and

change in feeding pattern. Incidence in DS is 1 %

RESPIRATORY Increase risk for respiratory infections

like RSV. Can see OSA even in infants Screening:

Car seat study to assess for apnea, bradycardia and oxygen desats (h/o cardiac surgery, hypotonia)

Sleep study recommended for all children by age 4 or sooner if symptomatic.

23-valent penumococcal vaccine at >2yrs if chronic respiratory or cardiac issues.

THYROID Congenital Hypothyroidism (1%) Check TSH. Newborn screen may only

include thyroxine (T4) - Many children with DS have mildly elevated TSH and normal T4.

Discuss with endocrinologist.

ANTICIPATORY GUIDANCE-NEWBORN Susceptibility to respiratory tract

infections Cervical spine positioning precautions

(Anesthesia, surgery, radiology) Refer for early intervention. Family support organizations. Individual resources for support (friends,

clergy). Recurrent risk in subsequent pregnancies Complementary and alternative

treatments (safe and dangerous)

1-12 MONTHS

HEARING Review serous otitis media (50-70%) Review prior hearing test

(BAER,ABR,OAE) If passed, re-screen at 6 months. If failed, refer to otolaryngologist. If tympanic membrane not visible, refer

(and then follow-up every 3-6 months). Treat middle ear dysfunction promptly

VISION Refer to ophthalmologist by

6 months to evaluate for strabismus, cataracts, nystagmus

Check vision at each visit Lacrimal duct obstruction,

refer for evaluation and surgical repair if not resolved by 9-12 months.

CARDIACMonitor infants with heart defects (VSD or AVSD) with shunting for symptoms of CHF Tachypnea, feeding difficulties, poor weight gain.Nutritional support until surgery(NEW) If large VSD without obstruction to pulmonary blood flow, repair by 4 months of age to prevent pulmonary HTN.There is risk for pulmonary HTN even without cardiac defects.

ANEMIA Incidence is 3% Hemoglobin by age 1, then annually. Children with DS have lower dietary iron

than peers. MCV is elevated. Serum ferritin and CRP or reticulocyte

count should be checked for kids with low iron intake.

OTHER CONCERNS Growth monitor for weight, weight/height or

BMI (NEW) Don’t use Down syndrome charts DS charts are currently being revised.

Cervical spine instability Signs of myelopathy, careful exam and

history. Discuss maintaining neutral spine for procedures.

OSA: Discuss symptoms and refer to specialist if symptoms are present

Monitor for infantile spasms (1-13%)

Check TSH at 6 months,1 year

Immunizations -Age based and Influenza vaccination for the year

Cont.

ANTICIPATORY GUIDANCE 1-12 MONTHS Support groups Assess emotional status of parents,

intrafamilial relationships, educate/support siblings. Review early intervention Discuss recurrence and prenatal testing

at least once in first year.

1-5YRS OF AGE

HEARING Review risk of hearing loss (30-50% age

3-5) Behavioral audiometry & tympanometry

every 6 months until ear-specific normal hearing.

Annual hearing test Alternatively, BAER or OAE Refer to otolaryngology if hearing loss

VISION Check at every visit. Annual ophthalmology

evaluation 50% chance of refractive

errors leading to amblyopia between age 3-5

ATLANTOAXIAL INSTABILITY Incidence 1-2% Discuss at least every 2 yrs

C-spine positioning for anesthetic, surgical, radiographic procedure.

Careful history and physical

SYMPTOMATIC CHILDSymptoms parents should seek urgent medical attention Change in gait or use of arms or hands Change in bladder or bowel function Neck pain, stiff neck, head tilt, torticollis,

change in head position Change in general function WeaknessLateral x-ray in neutral only (NEW). if abnormal – urgent referral to neurosurgery or

orthopedic surgery If normal – flexion/extension films, prompt

referral

ASYMPTOMATIC CHILD X-rays do not predict risk or reassurance -

Routine x-rays NOT recommended (NEW) Participation in some sports increases risk -

football, soccer, diving, gymnastics (older kids)

Special Olympics may still require films.

OSA Incidence (50-75%) Symptoms -Heavy breathing, snoring,

restless sleep, uncommon sleep positions, frequent night awakening, daytime sleepiness, apneic pauses, behavior problems.

BUT poor correlation parent report with OSA.

(NEW) Sleep study for all kids with DS by age 4.

Refer to specialist. Discuss obesity as the risk factor.

CELIAC DISEASE Incidence 5% Symptoms -Diarrhea, protracted

constipation, slow growth , FTT, anemia, abdominal pain or bloating or refractory developmental or behavioral problems.

If symptoms present, check tissue transglutaminase IgA and total IgA.

If abnormal, refer to gastroenterologist. No evidence to support screen if

asymptomatic.

OTHER CONCERNS TSH annually Cardiology: follow up after repair. Neurology: monitor for seizures. Anemia: Check hemoglobin annually. Ferritin and CRP if risk for iron deficiency.

ANTICIPATORY GUIDANCE 1-5 YRS Early intervention (OT, PT, Speech) Transition to preschool Behavior or social progress. Refer if suspicion for autism, ADHD or other

psychiatric or behavioral problem. Vaccination-PCV 23 at 2 yrs or older if

chronic cardiac or pulmonary disease. Reassure regarding delayed dental and

irregular dental eruption. Encourage and model accurate terms for

genitalia and respect for body parts Counsel re: increased risk of sexual

exploitation.

PSYCHOSOCIAL CONCERNS Sibling adjustment, behavioral

management. Socialization, recreational skills Child’s education program -Learning

problems -IEP

OTHER CONSIDERATIONS Review family dietary habits and

physical activity pattern. Obesity -Snacks and Television

watching. SSI and Medicaid benefits. Investigate trust and guardian

arrangements. ARC (Association of retarded citizens)-

financial and custody arrangements.

5-13Y

5-13 YEARS Review symptoms related to celiac

disease. Cervical spine: review precautions.

Instruct family to call immediately if new symptoms of myelopathy.

C-spine and sports: Counsel on increased risk with some sports.

Dry skin: sign of hypothyroidism. Discuss symptoms of OSA. Refer if signs

or symptoms are present. Discuss obesity as a risk factor

ANTICIPATORY GUIDANCE 5-13YRS Review development, appropriateness

of school placement. Discuss socialization, family status and

relationships, including financial arrangements, health insurance and guardianship.

Discuss development of age appropriate social skills, self help skills and development of a sense of responsibility.

ANTICIPATORY GUIDANCE 5-13YRS Behavior problems that interfere with

function at home, school and community

Attention problems ADD/ADHD OCD Non compliant behavior Wandering off

Behavioral Intervention Community treatment program Psychosocial services consult Behavioral specialists -may be more

sensitive to medications. Improve or maximize expressive

language

Cont.

Transition to middle school. Independence with hygiene, discuss and

model privacy, management of sexual behaviors.

Pubertal changes, fertility, contraception (depot provera)

Gynecologic care, birth control, STDs

Cont.

AGE 13-21 Annual Hemoglobin. Annual TSH Ear specific audiology Check for celiac disease symptoms. OSA symptoms, refer if needed C-spine

Symptoms and precautionsSports

AGE 13-21 Eyes- Ophthalmology every 3 yrs

(cataracts, refractive errors, keratoconus which can cause blurred vision, corneal thinning, corneal haze)

Cardiac follow up. If new murmur or gallop or increased fatigue, SOB ( at rest or with exertion), get an echo to evaluate valves.

ANTICIPATORY GUIDANCE AGE 13-21 Transition issues (guardianship, long term

financial planning, adult morbidities) Growth: BMI, healthy diet, exercise Behavioral and social issues: refer if

chronic problem or acute deterioration School

placement, transition planning, vocational training.

Fertility: Discuss recurrence with females Gynecologic care

Personal care: Self-care, hygiene, sexual development, STDs ,contraception.

Living arrangements: group homes, independent living, workshops, community supported employment.

Family arrangements: Financial planning, guardianship

Transition to adult medical care.

Cont.

MISSOURI SUPPORT ORGANIZATIONS www.stlouischildrens.org/our-services/do

wn-syndrome-center/support-groups www.kcdsg.org/community_groups.php www.connectmidmissouri.com/news/stor

y.aspx?id=749947 www.ozarksdsg.org

RESOURCES

National down syndrome congress www.ndsccenter.org National down syndrome society www.ndss.org www.care.com Medical home -Accessible, continuous,

compassionate, family centered, coordinated, compassionate, culturally effective care.

Clinical Trials:

Effect and efficacy in treating with Donezepil hydrochloride for cognitive dysfunction

Vitamin E in aging persons with DS.

QUESTIONS?