A four-year-old girl with scoliosis presents with multiple, evenly pigmented, irregularly shaped brown macules, 10 mm to 30 mm in diameter on the back, torso and arms. The spots were present at birth but the patient’s mother reports that they have increased in prevalence over time. Further examination reveals several raised red skin tags and multiple small yellow-brown lesions on the surface of the iris.
Family history indicates that the father has freckling in his armpits and inguinal region and several nodular plexiform neurofibromas are present on his torso on examination. What’s your diagnosis?
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Neurofibromatosis type 1 (N1) is one of three genetically distinct nerve-associated tumor disorders that result from mutations to genes that play key roles in suppressing cell growth in the nervous system. Most N1 tumors are benign, but some may become cancerous.
The condition affects approximately 1 in 3,000 people, according to the National Institute of Neurologic Disorders and Stroke. Despite its low prevalence in the general population, N1 is one of the most common autosomal dominant genetic disorders in humans – meaning a child has a 50% chance of inheriting the disorder from a parent. Despite its genetic basis, 30% to 50% of new cases result from spontaneous genetic mutations of unknown cause.
Signs and symptoms
The presence of six or more café-au-lait spots (CLS) that measure more than 5 mm in diameter in children are often the first sign of N1. The spots are distributed randomly on the body, but do not occur on the eyebrows, scalp, palms and soles.
CLS are often present at birth, but tend to increase as time goes on. CLS in adolescents and adults measure 15 mm or more across, but tend to fade with time.
Axillary freckling is common in later childhood and adulthood. Skin abnormalities are almost always present by the time a child is 10 years old, but because the disorder progresses with age, it may take several years to make an official diagnosis.
Since CLS occur normally in about 10% of the population and are also present with other disorders, more clinical features must be used to diagnose N1.
Multiple small yellow-brown lesions on the surface of the iris, known as Lish nodules or multiple iris melanocyctic hamartomas, can aid in diagnosis as can the presence of optic nerve gliomas on magnetic resonance imaging. Some patients with optic gliomas can develop progressive vision loss as the tumor expands.
Skeletal involvement, including scoliosis, macrocephaly and short stature can also help clinicians identify the disorder in patients that have a more subtle manifestation of the disease.
Definite diagnosis is based on clinical presentation consistent with the National Institutes of Health diagnostic criteria. Patients with multiple CLS should be followed for the appearance of other NF1 symptoms.
Although not necessary for the disorder, family history and examining parents may be crucial in diagnosis.
NF1 is progressive and worsens over time. Neurofibromas can increase with age, causing cosmetic and psychological issues. In general most people develop mild to moderate symptoms and have a normal life expectancy.
There is no cure for NF1, so the main treatment goal is early detection, genetic counseling and intervention for various complications. Because the disorder often involves many organ systems, coordination between clinicians in different subspecialties is key.
Surgical interventions are available to remove tumors that may become cancerous, as well as those that cause cosmetic disfigurement, or to correct bone malformations. Radiation and chemotherapy may be necessary if a tumor is malignant, or to prevent vision loss from optic nerve gliomas.
1. Freedberg IM, Isin AZ, Wolff K, et al. Fitzpatrick’s Dermatology in General Medicine (5th ed.). 1999. New York: McGraw-Hill.