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. Smruthi Sanath, M.D. Pediatric Resident (PGY-3) University of Missouri at Columbia 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 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. Type Incidence Chromosome findings Physical 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 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, Advanced maternal age Having one child with DS previously Carrying the genetic translocation for DS First trimester Second trimester Quadruple screen: maternal age, B-hcg, unconjugated estriol, AFP, Inhibin (sens 80%) Integrated screen Early screening: maternal age, Nuchal fold, B-hcg, PAPP-A (sensitivity 82-87%) Combination of both (sens 95%) Diagnostic CVS, Amniocentesis 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 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 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. Cont. 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. National Down syndrome society -www.ndss.org. 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 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 Cont. 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. 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 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-forlength 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 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! Malformations (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%). 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 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 breathing If severe or cardiopulmonary compromise or feeding problemsrefer to pulmonologist. 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 % 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. 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. 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) 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 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. Monitor 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. 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. 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 Cont. Monitor Check for infantile spasms (1-13%) TSH at 6 months,1 year Immunizations -Age based and Influenza vaccination for the year 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. 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 Check at every visit. Annual ophthalmology evaluation 50% chance of refractive errors leading to amblyopia between age 3-5 Incidence 1-2% Discuss at least every 2 yrs C-spine positioning for anesthetic, surgical, radiographic procedure. Careful history and physical Symptoms 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 Weakness Lateral x-ray in neutral only (NEW). if abnormal – urgent referral to neurosurgery or orthopedic surgery If normal – flexion/extension films, prompt referral 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. 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. 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. TSH annually Cardiology: follow up after repair. Neurology: monitor for seizures. Anemia: Check hemoglobin annually. Ferritin and CRP if risk for iron deficiency. 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. Sibling adjustment, behavioral management. Socialization, recreational skills Child’s education program -Learning problems -IEP 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. 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 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. Behavior problems that interfere with function at home, school and community Attention problems ADD/ADHD OCD Non compliant behavior Wandering off Cont. 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 Annual Hemoglobin. Annual TSH Ear specific audiology Check for celiac disease symptoms. OSA symptoms, refer if needed C-spine Symptoms and precautions Sports 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. 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 Cont. 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. www.stlouischildrens.org/our-services/down- syndrome-center/support-groups www.kcdsg.org/community_groups.php www.connectmidmissouri.com/news/story.as px?id=749947 www.ozarksdsg.org 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.