(Initial Table Of Contents)

The following are visual aids you might find useful when visiting with families prior to a genetic consultation or following their visit. If the title is followed by an asterisk the figure is one that was included in the text. Also included in this appendix is the Huntington disease testing protocol and a fact sheet on neurofibromatosis. These last two items are provided as prototypes.

CONTENTS Visual Aids:

Normal Female Karyotype* D-1

Trisomy 21 Male Karyotype D-2

Autosomal Dominant Pattern of Inheritance* D-3

Autosomal Recessive Pattern of Inheritance* D-4

X-Linked Pattern of Inheritance* D-5

Translocation Diagram* D-6

Maternal Serum Screening* D-7

Presymptomatic Huntington Disease Testing D-8

Protocol

Neurofibromatosis Fact Sheet D-10

Appendix D: Educational Tools

PRESYMPTOMATIC HUNTINGTON DISEASE TESTING PROTOCOL

The Birth Defects Genetics Center (BDGC) of the USD School of Medicine offers a presymptomatic Huntington disease (HD) testing program. This program is offered in conjunction with the Chapman Institute in Tulsa, Oklahoma.

HD is a genetic condition which results in progressive dementia and neurologic deficit, with symptoms most often appearing in the 3rd or 4th decade of life. At-risk individuals may wish to know their carrier status prior to the onset of symptoms. This testing program is designed to allow appropriate individual testing in conjunction with psychosocial and medical follow-up care.

Individuals interested in testing must follow a set protocol. Six or more visits may be necessary to complete the protocol. The first visit may take place at any one of the Birth Defects Genetics Clinic sites (Sioux Falls, Pierre, Aberdeen, Rapid City). The rest of the visits will take place in Sioux Falls.

The protocol outline is as follows:

The at-risk individual needs to contact the BDGC. A clinic appointment will be made and release of medical records, pedigree and other forms will be sent to the patient for completion.

Visit #1 Genetic Consultation:

The first visit involves reviewing affected family members' medical records, pedigree analysis, genetic counseling, and a discussion of the DNA testing procedure and test limitations. The patient will need to identify a companion and counselor close to home. The patient may need to discuss testing with family members.

If the patient wishes to proceed further he/she will contact the clinic for a follow-up appointment.

Visit #2 Psychiatric Evaluation:

The psychiatric and psychometric testing may require two visits. Psychiatric findings will be discussed with the patient.

Visit #3 Neurologic Evaluation:

A neurologic evaluation generally requires one visit with additional diagnostic studies as needed. Neurologic findings will be discussed with the patient.

Visit #4 DNA Testing:

Consent and release of information forms need to be signed. Blood will be drawn from the patient. A companion and a counselor will have been selected.

Visit #5 Test Results:

Test results will be disclosed to the patient and companion. A counseling session will be scheduled in 7 to 10 days.

A follow-up telephone call will be made the following day.

Visit #6 Follow-up counseling sessions or psychiatric evaluation as needed.

A patient may choose to stop testing at any time. This would not prejudice the relationship with the Genetics Clinic staff. The program is strictly voluntary. There are times when the Clinic staff may choose to stop testing. The reasons for this will be discussed with the patient.

The discovery of the HD gene has made testing easier. Nonetheless, presymptomatic testing requires a great deal of forethought. There is currently no cure.

Persons wanting more information may contact Patty Skorey-Solberg at 605-677-5623 or Carol Christianson at 605-394-5110.

Neurofibromatosis 1 (NF1), the classic form of neurofibromatosis, has an incidence of 1 in 4,000 newborns. The NF1 gene (neurofibromin) is a large gene, possibly up to two million bases. It was discovered on chromosome 17q in 1990. NF1 is associated with cafe-au-lait spots, benign tumors (neurofibromas), occasionally malignant tumors, learning disabilities, skeletal problems, and other neurologic symptoms. It is a dominant trait with variable expressivity. Fifty percent of affected individuals have a new mutation.

DIAGNOSTIC CRITERIA

• Six or more cafe-au-lait spots over 5 mm (prepubertal) , over 15 mm (post-pubertal)
• Two or more fibromas of any type or one plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Optic glioma
• Two or more Lisch nodules (on the iris)
• Bone lesions such as sphenoid dysplasia, thinning of the long bone cortex, pseudoarthrosis
• A first degree relative (parent, sib or offspring) with NF1

GENETIC COUNSELING

• An affected patient/parent has a 50% recurrence risk for each child; there is great variability in clinical expression within a family. Risk recurrence for normal parents or normal sibs (following a thorough examination) is small to negligible.
• Prognosis is highly variable, benign in some individuals, serious complications in others. The risk of progression may be greater in puberty and pregnancy.
• Psychological adjustment needs to be addressed considering the anxiety of complications or disfigurement and anxiety over social acceptance.
• Resources including support groups, national organizations, specialized clinics, state welfare services, and educational resources need to be explored.

HEALTH CARE SUPERVISION AND FOLLOW-UP

• History-inquire about neurologic deficit, recently acquired or progressive hearing problems, vision problems, pain or paresthesia, psychomotor and cognitive deficits.
• Physical examination-neurological examination for focal or asymmetric findings, hearing evaluation, visual examination including confrontational visual field examination, skeletal anomalies including scoliosis, range of movement of joints, palpable skeletal lesions, short stature, precocious puberty or hypogonadism, hypertension, cafe-au-lait spots, head circumference and size, number and location of neurofibromas.
• Ancillary tests-imaging studies such as MRI and CT scans are indicated only if there are relevant symptoms; neuroimaging studies are not the norm. Intermittent unexplained hypertension may require diagnostic studies to rule out pheochromocytoma. Changes in spine or joints may require x-ray confirmation. A sudden increase in size of a tumor or worsening of associated symptoms may require surgical referral.
• Annual follow-up examination is recommended to monitor the above findings with emphasis on development of new symptoms or progression of deficits.
  
• (Initial Table Of Contents)