Genetic Counseling
Contracting
As with other genetic counseling indications, ascertaining the family's understanding of the reason for the visit as well as their primary questions and concerns, and mutually developing a plan to address these concerns, are key components of establishing rapport in the neurofibromatosis (NF) counseling process.
Medical and Developmental History
See Figure 1 in the original guideline document for a sample clinic intake form.
Family History
To identify additional family members who may be affected with NF, obtain at least a three generation, targeted pedigree from the consultand or proband using standardized pedigree symbols. When possible, verify positive or questionable family history with medical records.
Suggestions for a targeted family history (these targeted questions may also aid in differential diagnosis):
- Birthmarks or other targeted skin findings
- Benign growth or tumors
- Malignant tumor or cancer
- Significant hearing problem such as hearing loss or ringing of the ears
- Significant vision problem such as tumor, poor vision, or blindness
- Bone or joint problems (fractures, dislocations, curved spine)
- Developmental delay, learning disability, attention deficit hyperactivity disorder (ADHD) or mental retardation (MR)
- Seizures, epilepsy or other nervous system problems
- Macrocephaly
Psychosocial Assessment and Counseling
Similar to genetic counseling for other conditions, obtaining a thorough psychosocial history and assessment is critical to the NF counseling process.
Suggestions for a Targeted Psychosocial History/Assessment
- Level of education
- Possible barriers to communication, including cultural/language diversity or the presence of learning disabilities
- Current level of knowledge regarding diagnosis of neurofibromatosis Type 1 (NF1)
- Family's understanding and perception of medical information
- Previous experiences with NF1, if any
- Family's perception of the etiology of NF1
- Emotional reaction to the diagnosis of NF1
- Family structure and functioning
- Family and community support systems
- Coping skills
- Meaning of a genetic diagnosis for the family, including implications for family planning and parenting
In addition to topics that are covered during a typical genetic counseling session, individuals with NF1 may have some unique psychosocial concerns that need to be addressed.
- Realize that many individuals have received information about NF1 from other sources (Internet, physicians, etc.), and that this information may be inaccurate, outdated, or only representative of the most severe cases of NF1.
- Recognize that the list of potential complications associated with NF1 is extensive. Appreciate that the information may be overwhelming for some individuals. The genetic counselor should use his or her clinical judgment in gauging the appropriate amount of information discussed during a session and may wish to continue discussions at subsequent appointments.
- Assess perception of the risk for malignancy. The term "tumors" can be especially frightening and it should be stressed that most NF tumors are benign. Malignancy risks should be discussed in the context of the general population's cancer risk, which is approximately 41%.
- Address concerns and fears regarding the variable and unpredictable natural history of NF1. Explain that the majority of individuals lead productive lives, meaning that they are able to attend school, be employed, and live independently. Providing the family with a list of concerning symptoms (See "Education," below) can be helpful in giving the family a sense of control when they are experiencing anxiety about the unpredictable nature of NF1.
- Assess perception of the impact of NF1 on the individual's daily life, with a focus on cosmetic and medical concerns.
- Discuss family's concerns regarding labeling and self-fulfilling prophecies. Many parents are concerned that the diagnosis of a genetic condition will lower a child's self-expectations or the expectations of others for the child.
- Assess the family's knowledge and perception of the Elephant Man. Despite the current belief that "The Elephant Man" did not have NF1, older literature and resources often refer to NF1 as the disease of "The Elephant Man." Families of patients with NF1 may still be affected by the association of NF1 with the difficult life of Joseph Merrick.
- Elicit the individual's experiences at school, work and other social situations. In addition to the learning disabilities, many NF1 patients have difficulty with social skills. This may also be impacted by the co-occurrence of ADHD.
- Be aware of issues regarding counseling an individual with a learning disability. In familial cases of NF1, a parent may also have a learning disability. This may affect an individual's understanding and perception of the disorder, their ability to recognize or cope with the potential medical issues, and their comprehension of the genetic implications for future offspring. In these families, it is particularly important to determine the level of understanding and adjust the counseling session to reflect the family's comprehension level. It is also important to keep in mind that individuals with learning disabilities may prefer alternate methods of receiving information and may benefit from reinforcement at follow-up visits.
- As indicated, assist the family in navigating the complexities of special education and/or other interventional services. Many individuals with NF1 require additional services in school, and obtaining these services may prove challenging and frustrating.
Risk Assessment
In order to complete an accurate risk assessment, it is crucial to determine whether the disease and/or mutation was inherited or de novo. This can often be accomplished through physical and ophthalmologic examination of the proband's parents. Alternatively, if a DNA mutation has been identified in the patient, molecular genetic testing can be performed.
If the Mutation is De Novo
Risk for siblings of proband is low (thought to be less than 1%), but remains increased due to the possibility of germline mosaicism (see "Special Considerations," below).
If the Mutation is Familial
Apply principles of autosomal dominant inheritance to pedigree. All offspring of an affected parent have a 50% risk to inherit the mutation. As indicated, identify nearest genetics/NF clinic for affected relatives not living in the area.
Education
Clinical Features and Natural History
Review the main features of the condition, its natural history, and the typical timeline for the development of features. See "Natural History" in the original guideline document.
Inheritance Pattern and Recurrence Risk
NF1 is an autosomal dominant condition. Approximately 50% of NF1 cases are inherited from a parent. The remaining 50% of cases of NF1 are due to a de novo mutation in the proband. This is felt to be due, in part, to the large size of the NF1 gene, which makes it more susceptible to mutation. Penetrance is essentially 100%, but expressivity is variable, even amongst family members. If neither parent of the proband has NF1, the chance of recurrence is low. However, because of the possibility of germline mosaicism, the recurrence risk is likely somewhat higher than the general population risk (see "Special Considerations" below).
Please see "Variants of NF1" in the original guideline document for recurrence risks for segmental NF.
Prenatal Testing and Reproductive Options
Prenatal molecular genetic testing is available for families in which the mutation has been identified in the proband. Alternatively, if there are multiple affected family members, and linkage has been established within the family, linkage analysis is an option. In these situations, prenatal diagnosis is possible via chorionic villus sampling (CVS) or amniocentesis. In the vast majority of cases, ultrasound is not useful in the prenatal diagnosis of NF1. There are some reports of prenatal identification of NF1-related abnormalities. These abnormalities included cardiac and craniofacial anomalies as well as tumors. However, the abnormalities included in these reports were atypical for NF1, and in only one instance was the diagnosis of NF1 considered before birth.
Given the variability and unpredictable nature of the condition, genetic counseling is critical for a couple considering prenatal testing for NF1. Genetic counseling informs a couple about the signs, course, and genetics of NF1. It also facilitates the discussion of personal, moral, and ethical issues they need to explore in order to make an autonomous decision that meets their needs.
Alternate Risk Reduction Options
In families where a parent is affected and the risk to offspring is 50%, various options can reduce the risk in a future pregnancy. The use of assisted reproductive technology with a donor gamete from an unaffected individual in place of the gamete from the affected parent can greatly reduce the risk to future children. Alternatively, preimplantation genetic diagnosis (PGD) may be available for couples in which the causative NF1 mutation has been identified or if linkage phase has been established.
Signs and Symptoms that Warrant Immediate Referral and Evaluation
Parents and patients often find it helpful to be informed of what types of symptoms warrant an immediate referral and evaluation.
Signs/Symptoms Warranting Immediate Referral
- Pain of unknown etiology
- Weakness, numbness, tingling in the extremities
- Change in balance or coordination
- Change in vision
- Change in intensity or frequency of headaches
- Neurofibromas that change rapidly in size and/or color, or cause pain
- Abnormal neurologic exam
- Sudden onset of hypertension
- Regression of cognitive skills or loss of developmental milestones
- Significant deviation from individual's established pattern of growth
Follow-up
Management
Management recommendations for patients with NF1 vary between centers and must be tailored to the individual. It is not the intention of this guideline to address specific management recommendations. It should be noted, however, that management of these patients typically requires a multidisciplinary team. Disciplines that may be involved in the care of a patient with NF1 are listed in Table VIII in the original guideline document.
Documentation
Providers are encouraged to thoroughly document all patient interactions. This may be done via a patient summary letter and/or a physician note. In many centers, these two forms of documentation are combined. Please see Table IX in the original guideline document for a list of suggested items to be included.
Special Considerations
Germline Mosaicism
Germline mosaicism is a recognized phenomenon occurring in a number of dominant genetic disorders and has been observed in NF1. Therefore, caution must be used when discussing recurrence risks with the parents of a child with an apparently de novo case of NF1, even if parental lymphocyte analysis is negative following mutation identification in the proband. Nevertheless, it is estimated that the risk for recurrence due to germline mosaicism is less than 1%.
Consent for DNA Testing
Informed consent for molecular analysis should be obtained from the patient or legal guardian prior to the acquisition of a sample for DNA testing. A consent form from the clinical testing laboratory should be reviewed with the family. Typically, this form describes the limitations and benefits of testing, how results will be reported, and any other potential uses of the specimen.
Patient Resources
It is important to aid the family in identifying additional sources of supports, such as advocacy and support groups, and other families. A list of patient resources in listed in Table X in the original guideline document.
