The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the state of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice.

1. Review patient/family questions; reason for referral; knowledge base; perception of disease status and/or risk; what diagnoses have been considered; perceived notion about causation; assess need for professional interpreter: Families may not be aware that newborn screening is routine.

2a. Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history.

b. Additional directed family history: stillbirth, hydrops fetalis, neonatal or early childhood death, chronic fatigue, anemia, hepatomegaly, splenomegaly, pain crises, recurrent abdominal pain, recurrent hospitalizations, transfusions, MR.

c. Obtain relevant medical records on patient, including records of 1).appropriate tests/evaluations:

newborn screening results; quantitative hemoglobin electrophoresis; CBC with indices; DNA studies of alpha or beta hemoglobin genes; iron studies, brilliant cresysl blue (BCB) stain , 2). records bearing on management , and 3). on other family members as needed: newborn screening results; quantitative hemoglobin electrophoresis; CBC with indices; DNA studies of alpha or beta hemoglobin genes; iron studies, brilliant cresysl blue (BCB) stain.

3. Obtain prenatal and perinatal history of patient, including prenatal exposures, pregnancy complications and prenatal testing, when appropriate.

4. Obtain past medical history (including environmental/occupational exposures) focusing on:

5. Obtain information on growth and development, including school placement. For adult, also obtain information on education, employment and social functioning.

6. Assess family functioning and use of community resources. Assess personal, social, religious, ethnocultural issues.

7. Assess possible ethical concerns, such as confidentiality, non-paternity, insurability, discrimination, prenatal diagnosis: religious beliefs

8. Perform general physical examination of patient and/or other family members present if indicated, with attention to:

9. Other issues to consider:

(this may occur in a series of multiple patient visits)

1. Summarize information obtained and discuss with patient/family the (possible) diagnosis and the degree of certainty of the diagnosis based on available information: Importance of knowing carrier status own for reproductive decisions and for other family members.

2. a. Recommend relevant tests/evaluations on patient and/or on other relatives which may include:

b. Discuss sensitivity/specificity of test(s)/evaluation(s): based on diagnosis of specific hemoglobinopathy

3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures (if homozygote or compound heterozygote): Define hemoglobin, RBC, and discuss the difference between hemoglobin and blood type. Discuss the likelihood that signs or symptoms may develop.

4. Review inheritance pattern (including penetrance and expressivity): Disease: Autosomal recessive with variable expressivity

5. Assess and discuss recurrence risk for future pregnancies, for affected and at risk individuals. Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others:

6a. Discuss reproductive options (e.g. assisted reproductive technologies, adoption, taking risk and no additional pregnancies) when appropriate:

b. Discuss prenatal diagnostic options/issues: refer to Prenatal CE

(or referral for discussion of)

7. Review management recommendations/options including screening protocols:

8. Consider referral to:

(medical specialties)

9. Address psychosocial issues including anticipatory guidance, patient and family reaction to diagnosis, need for community support services: employment discrimination with AS carriers in Airline industry

10. Address follow-up issues, such as genetic counseling for extended family members, including a plan for relaying test results:

11. Document clinic visit, including persons present, and subsequent substantive contacts (e.g. clinic note, +/- letter to referral source, +/- letter to family; other).

12. Other issues to consider:

13. References and/or other protocols:

The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the state of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice.

1. Review patient/family questions; reason for referral; knowledge base; perception of disease status and/or risk; what diagnoses have been considered; perceived notion of causation; assess need for professional interpreter: Families may not be aware that newborn screening is routine.

2a. Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history.

b. Additional directed family history: stillbirth, hydrops fetalis, neonatal or early childhood death, chronic fatigue, anemia, hepatomegaly, splenomegaly, pain crises, recurrent abdominal pain, recurrent hospitalizations, transfusions, MR.

c. Obtain relevant medical records on patient/affected family member(s), including records on appropriate diagnostic testing/evaluation newborn screening results; quantitative hemoglobin electrophoresis; CBC with indices; DNA studies of alpha or beta hemoglobin genes; iron studies, brilliant cresysl blue (BCB) stain: and on other family members as needed: newborn screening results; quantitative hemoglobin electrophoresis; CBC with indices; DNA studies of alpha or beta hemoglobin genes; iron studies, brilliant cresysl blue (BCB) stain

3. Obtain patient's past and current pregnancy history; documenting gestational age, Rh, prenatal exposures, pregnancy complications and pertinent prenatal testing to date.

4. Obtain patient's past medical history.

5. Obtain information on education, employment and social functioning as appropriate.

6. Assess family functioning and use of community resources, as appropriate. Assess personal (e.g. social, ethnocultural, religious) issues, including feelings about prenatal testing and consequences.

7. Assess ethical issues, such as confidentiality, insurability, discrimination and non-paternity:

8. Other issues to consider:

1. Interpreters trained in hemoglobinopathy counseling may be required.

2. Culturally sensitive interactions with family, and appropriate counseling tools needed.

3. Father not available or unknown.

Information to be provided or discussed with patient/family

(this may occur in a series of multiple patient visits)

1a. Discuss risk of specific condition occurring in current pregnancy based on information available. Arrange for additional tests/evaluations on consultand and/or father of the baby if indicated: Dependent on availability of father’s test results (see page 1, #2c).

b. Discuss sensitivity/specificity of test(s)/evaluation(s): especially sickledex, DNA- numerous mutations

c. Discuss referral of other family members for genetic testing/evaluation if inheritable disease is suspected and confirmation is necessary.

2a. Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others:

b. Discuss inheritance pattern of disorder, including risk for future pregnancies:

3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications (e.g. hematuria may be more common in AS carriers), including pregnancy related risks for affected women if indicated, and preventive measures:

Define hemoglobin, RBC, and discuss the difference between hemoglobin and blood type. Discuss the likelihood that signs or symptoms may develop.

4a. Review prenatal testing options as indicated: for couples identified at risk for a disease in the fetus because both are hemoglobinopathy carriers of the same mutation or mutations that would interact adversely, or when at risk fetus cannot be ruled-out (e.g. father not available)

b. Discuss risks and limitations of prenatal testing options, including sensitivity/specificity of test method(s):

5. Explore psychosocial impact of testing vs. non-testing, ethical issues, and discuss the decision making process. Refer to outside resources as appropriate to help with decision making. (Process includes the discussion of outcomes/results, additional testing, option of termination of pregnancy, pediatric follow up, and support groups).

6. Document status of decision making by patient/family.

7. Make arrangements for testing if desired and plan for relaying results and for follow-up.

8. Consider referral to specific community resources and support groups.

9. Document the clinic visit, including persons present, and subsequent substantive contacts (e.g. clinic note, +/- letter to referring source, +/- letter to family, other).

10. Other issues to consider: carrier status of other family members; need to offer counseling and carrier testing to them

11. References and/or other protocols: