1. Taking Care of the School Aged Child with a Genetic Condition Susan Fernbach, RN, BSN Director of Genetic Outreach Baylor College of Medicine Texas Children’s Hospital fernbach@bcm.edu

2. Objectives  Describe the most common genetic conditions impacting the school aged child  Discuss signs & symptoms of 2 common genetic conditions  Describe the role of the school nurse  Identify 3 national genetic resources

3. Introduction  Genetic disorders are individually rare but collectively very common and seen throughout the lifespan  Have a significant impact on total hospitalizations and health care needs  Early diagnosis important to improve long-term outcome

4. Common genetic conditions impacting the school aged child  Chromosome abnormalities Down Syndrome 1:700 children  Sickle Cell Anemia: 1 in 625  Cystic Fibrosis 1:3300  Neurofibromatosis 1: 3500  Duchenne Muscular Dystrophy 1:3500

5. Common genetic conditions impacting the school aged child  Marfan Syndrome affects 1-2:10,000 people  VeloCardioFacial Syndrome affects 1: 2000 to 1:4000 people

6. Introduction to Genetics: Chromosomes, DNA, and Genes Cell Nucleus Chromosomes GeneProtein

7. Chromosomes: normal female

8. Chromosomes: normal male

9. Down syndrome

10. Chromosome Microarray Analysis (CMA)  CMA is a new lab technology to analyze the chromosomes for a large number of genetic disorders.  CMA has greater sensitivity than older methods of chromosome analysis.

11. Trisomy 21 (Down syndrome) Karyotype X 20 22 21 GainLoss

12. Marfan Syndrome  Inherited disorder of connective tissue: abnormal protein causes weaker connective tissue throughout body  Mutation or change in fibrillin gene on chromosome 15  Affects males/females  Affects all ethnic groups  Described by Dr. Antoine Marfan in 1896  Symptoms variable, range from mild to severe

13. Clinical Features  Skeletal abnormalities  Cardiac manifestations  Eye abnormalities

14. Skeletal abnormalities  Long narrow face with high arched palate.  Disproportionately long fingers and limbs  Chest abnormalities, pectus excavatum or pectus carinatum  Scoliosis- seen in about 50%  Joint hypermobility

15. Cardiac Features  Aortic dilation and aortic aneurysms  Predisposition for aortic tear and rupture  Mitral valve prolapse  Aortic regurgitation

16. Eye Findings  Dislocated Lens  Myopia  Detached Retina

17. Evaluation: complex  Physical exam  Family history  Echocardiogram  Ophthalmologic exam

18. Cause  Mutation or change in fibrillin gene on chromosome 15.  This gene tells the body how to make the fibrillin-1 protein needed by connective tissue  Affects eyes, heart, lungs, skin, skeletal system

19. Diagnosis  Diagnosis based on physical criteria, not genetic testing  Fibrillin gene on Chromosome 15 causes Marfan syndrome. Over 300 mutations in this gene have been found.  Testing currently expensive and may not detect a mutation.

20. Inheritance  Autosomal Dominant  75% have an affected parent  25% due to a new mutation or change

21. Genetic Counseling  If familial, siblings have a 50% risk  If new mutation, siblings have low risk  Any child of the affected person will have a 50% chance to be affected

22. Treatment may include:  Antihypertensives  Surgery  Anticoagulants  Headache and/or pain management  Antidepressants

23. Physical Activity Guidelines  Want non-contact, non-strenuous, non-competitive activities  Encourage brisk walking, slow jogging, cycling on level ground, shooting baskets, slow paced tennis.  Backpacks can be heavy, may want to have a 2 nd set of text books at home.

24. Athletics  Avoid competitive sports, weight-lifting  Guide children away from sports at a young age  Encourage them to become active in other areas: computers, music, drama or team managing

25. Case history malefemale 12 mo. old

26. Role of the School Nurse  Screening: vision, posture, BMI, Pre-Sports physicals  Refer: convey need to parents, help with referral, follow-up  Manage medicines, psychosocial  Help student learn to communicate health concerns or needs  Educate teachers/parents  Support and follow-up

27. How to recognize emergencies  Aortic rupture or dissection: rare in school aged child. Usually painful, has been described as ‘tearing pain boring through’. May have syncope or shortness of breath.  Pneumothorax: shortness of breath, pain  Retinal detachment: flashing lights, spots in vision, sudden loss of vision

28. Have Emergency Plan -Physician and insurance information -List of all medications -Keep document on hand with current clinical status -Date of last ECHO and findings -List all surgeries to date -Hospital the child should be transported to in the event of an emergency.

29. Lifespan With early diagnosis and ongoing treatment, life expectancy close to normal.

30. Resources  National Marfan Foundation Offer free DVD for school nurse www.marfan.org  Current clinical research studies www.clinicaltrials.gov

31. VeloCardioFacial Syndrome  VeloCardioFacial Syndrome (VCFS) is also called DiGeorge Syndrome or 22q11.2 deletion syndrome  Is a microdeletion syndrome  Even tiny losses of genetic material can be the cause of a genetic syndrome  Affects males/females  Affects all ethnic groups

32. A Short History  1965 Dr. DiGeorge describes children with low calcium, seizures, infections & heart defects.  1978 Dr. Shprintzen describes a condition running in families. Patients have cleft palate or velopharyngeal incompetence, heart defects, learning disabilities & characteristic facial appearance. He calls it velocardiofacial syndrome.  1992 DGS & VCFS found to be due to deletion 22q11.2

33. Deletion 22q11.2 DiGeorge Syndrome Velocardiofacial Syndrome  Presenting in infancy  Severe heart defects Often lethal  Severe infections Immunodeficiency  Seizures Low calcium levels  Childhood/adulthood  Heart defects Usually mild  Weak palate; cleft palate Nasal voice  Long face and fingers

34. Microdeletions 22q11.2 VCFS Characteristics  Over 180 physical & developmental characteristics reported:  Heart defects: (80%) (VSD, DORV, TOF)  Cleft palate (75%)  Prominent nose  Small and cupped ears  Renal abnormalities (>30%)  Learning disabilities, mild mental retardation: IQ ~ 80  Psychiatric illnesses (>40 %): schizophrenia, bipolar disorder

35. No feature occurs in all children No child has all of these features. The medical, developmental & psychological features are very different from person to person. Range from severe to mild. Characteristics

36. Evaluation  Physical exam and presence of signs and symptoms of VCFS  Blood test: Chromosome microarray testing

37. VCFS is a microdeletion  Microdeletion Too small to be seen with routine chromosome studies 10-100 genes in a row deleted Detected with new chromosome microarray test

38. Chromosome Microarray Analysis Abnormal signal from the microarray very tiny deletion of the genetic material 22q11 deletion syndrome

39. Inheritance  Autosomal Dominant  ~ 90% are new deletion in family  ~ 10% are inherited from a parent

40. Genetic Counseling  When a child is diagnosed with VCFS, testing the parents is also recommended.  If a parent is affected, each of their children has a 50% chance to be affected.

41. Treatment  Depends on symptoms: Surgery to correct cleft palate and/or heart defect Speech therapy Psychological counseling, psychiatric care Medication

42. VCFS Resources  International 22q Foundation: www.22q.org www.22q.org  VCFS Texas, Inc.: www.vcfstexas.com www.vcfstexas.com

43. Role of the School Nurse  Screening/ Identify  Refer  Management  Educate teachers/parents  Support and follow-up

44. Identify  Child with developmental disabilities, single gene disorder, heart defects  Multiple health problems  Tall or short stature or uneven body proportions  If a child has 3 or more minor anomalies, may have 1 or more major malformation Examples:  Facial features that are unusual or different from other family members  Ear abnormalities Unusually shaped eyes  Webbed fingers or toes Unusual birthmarks

45. Referral  Discuss with parents  Provide referral information Texas Children’s Hospital Genetics Clinic 832.822.4293 Children’s Memorial Hermann Genetics 832.325.6516 Genetic providers in Texas: www.dshs.state.tx.us/genetics/provider.shtm

46. Clinical Benefits of Genetic Evaluation  Anticipatory monitoring – ex: obtaining a kidney ultrasound for children with VCFS  Early intervention – ex: speech therapy for children with VCFS  Clinical screening of parents & brothers/sisters with VCFS, Marfan  Discuss recurrence risk for parents

47. How to prepare families for a genetic evaluation?  The first appointment may last ~1 ½ to 2 hours for physical exam, family history, detailed medical history, review previous tests, DNA tests may be ordered (blood sample)  Test results available in 2-3 weeks  A second appointment scheduled to review results and plan of care

48. Support  Support family through grieving with the child’s diagnosis of a genetic condition  Besides the feelings of numbness, helplessness, anger, denial, sadness, shame, there can be a great deal of guilt  Help parent see their child’s strengths and get help for the areas of weakness  Assess their understanding of the diagnosis and refer back to genetics clinic if needed  Help families connect with other families or support groups  Offer access to local, state, national resources

49. Web Resources  Genetic Home Reference: http://ghr.nlm.nih.gov/  Gene tests www.genetests.orgwww.genetests.org  March of Dimes. Genetics and Your Practice: www.marchofdimes.com www.marchofdimes.com  National Organization for Rare Disorders: www.rarediseases.org www.rarediseases.org  Texas Department of State Health Services: http://www.dshs.state.tx.us/genetics/pedi- genetics.shtm  Unique : www.rarechromo.orgwww.rarechromo.org

50. Summary  Genetic disorders are individually rare but collectively very common and may be seen throughout the lifespan  School nurse is a key person in identifying and referring children for evaluation of genetic condition

51. Know your own family health history! My Family Health Portrait: www.hhs.gov/familyhistory  Helps you know your risk of heart disease, diabetes, cancer  Take steps with your doctor to reduce your risk  Your family history is a gift to you and your health  If you are adopted, your health history will help your children and grandchildren