Neurofibromatosis Type 1: What Parents Should Know

Many children can be born with or develop one or more birth marks that can vary in size, color and shape, but do not usually pose any health risk. However, a certain number of darker spots (café au lait macules) or freckles on skin not exposed to the sun can often be the first indication of a genetic condition called neurofibromatosis type 1 (NF1).

NF1 is the most common neurological disorder caused by a change (or mutation) in a single gene, occurring in one in every 3,000 children. The majority of these children do very well, have happy and healthy lives and may not have major skin issues, developmental disabilities or other neurological issues, says Dr. Neda Zadeh a CHOC Children’s medical geneticist and associate director of the Molecular Diagnostic Laboratory at Genetics Center.

Zadeh, Neda

“Most of the time, NF1 can occur for the first time in a child due to a random genetic change at the time of conception, and is not inherited from a parent,” explains Dr. Zadeh. “It is important for parents to realize that this condition is not the result of anything an expectant mother did or did not do during her pregnancy. In about one-third of patients, we often will see that one of the parents also has NF1 and may not even realize it.”

In order to meet criteria for an NF1 diagnosis, patients must meet two of the following criteria established by the National Institutes of Health (NIH), summarized below:

  • Six or more café-au-lait macules of a specific measured diameter
  • Two or more neurofibromas or one plexiform neurofibroma
  • Freckling in the axillary or inguinal regions
  • Optic glioma
  • Two or more Lisch nodules on dilated eye exam
  • A distinctive bony lesion
  • A first-degree relative (parent, sibling, or offspring) with a known diagnosis of NF1.

The NIH criteria are extremely accurate in adults and children over the age of 5 years.  Often if children are younger than 5 at the first evaluation, he or she may not yet have met the above criteria, but may do so after they reach school age. For this reason, visiting a geneticist on a regular basis is important in order to monitor and care for the patient.  Also, in certain cases in which a diagnosis is not completely clear, or there is concern for a different diagnosis, genetic testing is available and usually coordinated after genetic counseling occurs.

If you are concerned that your child may have NF1, or there is a family history of this genetic condition, speak with your pediatrician, who will perform an evaluation and may refer you to a geneticist for further examination and information.

“Parents should be aware that 10 percent of adults may have one or two café au lait macules, which are simply birthmarks and no underlying genetic issue,” says Zadeh.

Neurofibromatosis type 2 (NF2) sounds very similar to NF1 in name, but is a completely separate disorder, and is even more rare than NF1, occurring in one in every 25,000 people worldwide. NF1 and NF2 are completely different conditions, caused by genes on different chromosomes, so having a child with NF1 does not mean they are predisposed to NF2, and vice versa.

Children with NF1 may require care from multiple specialists including neurosurgery, neurology, oncology and orthopaedics, but should be seen at least annually by a geneticist.

“Children with NF1 should be under the care of a geneticist, who can help coordinate care and management of NF1 patients,” says Zadeh. “We also can provide information regarding the possibility to have further children in the family with NF1 and referrals to complete genetic counseling.”

CHOC’s Neurofibromatosis Program has been treating children with NF1 for more than 30 years and annually treats at least 150 children with NF1. The clinic was recently recognized by the Children’s Tumor Foundation as a Neurofibromatosis Affiliate Clinic, recognizing the program for having all the necessary specialists needed in order to provide comprehensive care to even the most complicated and rare issues that can be seen in association with NF1. This special program is nationally recognized and CHOC specialists are currently involved in cutting-edge clinical trials that are not available at many pediatric centers.

Learn more about the genetics program at CHOC.

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Preventing & Screening For Birth Defects

In honor of Birth Defects Prevention Month, we spoke to Dr. Neda  Zadeh, a CHOC Children’s geneticist and the associate director of the Molecular Diagnostic Laboratory at Genetics Center.  Dr.  Zadeh specializes in caring for patients with developmental disabilities, genetic disorders and birth defects.

Zadeh, Neda

Q: What can parents do to prevent birth defects?

A: The cause of most birth defects is not well known.  Many are the result of a combination of genes and the environment.  Therefore the occurrence of a birth defect is not due to anything a parent did or did not do during the pregnancy.

The occurrence of certain types of birth defects involving the spine (spina bifida) can be reduced in a certain population of women who may have had a prior child with a neural tube defect. Most prenatal vitamins include 400-800 micrograms of folic acid, but a mother who has a prior child with spina bifida can be prescribed an increased dose of 4 mg per day, in addition to her prenatal vitamins.

Q: What screening can be done to detect birth defects before the baby arrives?

A: All pregnant women under 35 years of age and without any prior family history of a birth defect or genetic condition are offered prenatal screening  through their obstetrician’s office, to detect a fetal chromosome abnormality and/or birth defects.  Pregnant women over 35 years of age, or those with a prior child with a birth defect, or family history of a genetic condition; are recommended to seek genetic counseling to discuss both prenatal screening as well as prenatal diagnostic tests that are available.  During the genetic counseling visit, prior medical history for the couple is obtained as well as a three- generation family history. Other factors discussed include conditions that run in the family or those that could be more prevalent in certain ethnic groups to determine if any carrier testing is indicated.

Prenatal screening tests typically involve a sample of the mother’s blood at particular times during the pregnancy and are designed to detect specific birth defects and chromosome abnormalities. Part of the screening includes a special ultrasound performed during the first trimester, which only measures the back of the fetus’ neck (nuchal translucency).  If this measurement is enlarged, it may indicate a fetal organ defect, a possible fetal chromosome abnormality, or single gene disorder.  Around four to five months of pregnancy, a detailed ultrasound is performed that examines the entire fetus and is geared towards detecting any anomalies or birth defects.  Genetic counseling is offered in the event that a prenatal ultrasound reveals an abnormality, in order to provide further information to the couple.

Identifying a birth defect or chromosome abnormality prenatally is often advantageous to parents, so they’re not surprised when the baby is born.  Geneticists and genetic counselors can provide specific genetic counseling and additional support to expectant parents, including connecting them to a birthing center that has appropriately trained specialists who can specially care for the baby when it is born. Some centers also like to meet with the couple prior to their baby’s delivery to have a birthing plan in place, so that the couple feels comfortable and knows what to expect.

Not all genetic conditions or birth defects are diagnosed before a baby is born.  Some birth defects and genetic syndromes may not be diagnosed until childhood. Children with developmental delay or unique features may be referred to a geneticist for a comprehensive evaluation in order to determine if there is an underlying genetic condition.  Knowledge of an underlying genetic diagnosis is important, as it aids in providing better and more specific care to the child.

Q: How do birth defects affect the child’s family?

A: When a birth defect is detected during pregnancy, parents can experience emotional effects right away. Fear of the unknown can make it hard to enjoy the pregnancy. This is why it’s helpful to schedule follow-up visits with a provider, who are experts on their baby’s condition and can explain the diagnosis again, and answer any questions.  It may take several visits before parents feel comfortable in their understanding of the information being provided.

Parents should be connected to educational and support services upon diagnosis. In addition to connecting parents with resources in the community, including support groups, pediatricians can also make referrals to a CHOC geneticist, who can provide additional information and support.