A 14-year-old female came to clinic with a history of skeletal pain that had been increasing over the past year. She complained mainly of knee and ankle pain bilaterally, but also right hip pain. She was having difficulty walking but it got better with rest. Antiinflammatory medication gave some relief and some days the pain was worse or better. The past medical history showed intermittent medical care because of relocations. The family history was positive for arthritis in older family members. One sibling had some “spots” on their skin. The review of systems was negative for night sweats, weight loss, and specific joint warmth or swelling.
The pertinent physical exam showed a well-appearing female with normal growth parameters and vital signs. Visual acuity was 20/20 bilaterally. HEENT was positive for Lisch nodules. Heart, lungs and abdomen were normal. Skin showed multiple cafe-au-lait lesions more than 2 cm mainly over her trunk but also over the lower extremities. She had several 1-1.5 cm nodules that were soft and could be invaginated on arms/legs. She had one 1.5 cm lesion that was firm and was like “a bag of worms” on her arm. Axillary freckling was present bilaterally. Musculoskeletal examination showed normal range of motion in all extremities with no overlying warmth or swelling. She had no skin lesions overlying any joint. She had obvious thoracolumbar scoliosis with at least one curve to the left. Neurologically she had a normal examination but complained of pain in her knees when walking.
The diagnosis of scoliosis and probable Neurofibromatosis Type 1 were made. The pain was felt to be secondary to abnormal biomechanics. The patient’s clinical course showed that she had not been evaluated for either of these problems and so consultations to orthopaedics and physical therapy were made right away. A double thoraco-lumbar curvature of the spine was diagnosed and she was scheduled for surgery because of its severity. A geneticist was consulted and confirmed NF1 and her evaluations were being completed.
Neurofibromatosis Type 1 (NF1) is one of many neurocutaneous diseases. Also called phacomatosis, a review can be found at: What is the Epidemiology and Genetics of the Major Phacomatoses?
The key elements of NF1 and 2 are:
- Neurofibromatosis Type 1
- Epidemiology: 1:2500-3000 – most common phacomatosis
- Genetics: autosomal dominant with variable penetrance, associated with chromosome 17
- Neurological: various central nervous system tumors especially neurofibromas (often benign but may act malignant because of location or size, tumors may also degenerate into a malignant variant or cause other problems such as hypothalamic problems secondary to an optic chiasm tumor ), optic nerve tumors, pheochromocytomas, mental retardation
- Dermatological: neurofibromas, cafe-au-lait spots
- Other clinical features: Lisch nodules of eye, other congenital anomalies may be associated including bone (rib, vertebra) and renal artery stenosis.
- Radiological features: lesions tend to be more scattered in brain and more peripheral than tuberous sclerosis
- Neurofibromatosis Type 2
- Epidemiology: 1-33,000-40,000
- Genetics: autosomal dominant with variable penetrance, associated with chromosome 22
- Neurological: bilateral vestibular nerve schwannomas, brain meningiomas and dorsal root schwannomas
- Dermatological: various skin changes can be seen but are less consistently associated
- Other clinical features: eye lens opacities
Skeletal lesions in NF1 patients are often not the first abnormality that clinicians think of, but can be seen and include:
- Generalized skeletal abnormalities
- Smaller stature
- Focal skeletal abnormalities
- Scoliosis 10-26%
- Long bone dysplasia 1-4%, especially of the tibia
Musculoskeletal pain appears to be caused by the primary lesion or biomechanical problems occurs. Endocrine abnormalities also occur such as low 25-hydroxyvitamin D, low parathyroid hormone levels. There appears to be an inverse correlation with the number of dermal neurofibromas and the level of 25-hydroxyvitamin D.
Questions for Further Discussion
1. What are the diagnostic criteria for NF1?
2. What are the neurological problems associated with NF1?
3. What initial and scheduled evaluations are needed for patients with NF1?
- Symptom/Presentation: Pain
- Specialty: Genetics | Orthopaedic Surgery and Sports Medicine | Radiology / Nuclear Medicine / Radiation Oncology
- Age: Teenager
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010 Jan;12(1):1-11.
Online Mendelian Inheritance in Man. Neurofibromatosis, Type 1; NF1. John’s Hopkins University.
Available from the Internet at http://www.omim.org/entry/162200 (rev. 3/18/2012, cited 12/14/2012).
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital