A 16-year-old boy presented for evaluation of his worsening behavior at school. He was very hyperactive and had difficulty in paying attention. He had always required help with reading and language. Maternal pregnancy and birth history were unremarkable.
During the physical examination, the patient was noted to have 8 hyperpigmented macules ranging from 2 to 8 cm with smooth margins, 7 or 8 flesh-colored, nontender papules, and 3 nodules on the trunk (A). His mother had numerous similar lesions on her trunk (B). Neither son nor mother had any changes in vision, heart murmur, or bony deformity. A diagnosis of neurofibromatosis had been suspected by a previous physician but had not been confirmed.
Neurofibromatosis type I, first described by von Recklinghausen in 1882, is one of the most common autosomal dominant neurocutaneous conditions. The estimated incidence is 1 in 2500 to 3000 persons, independent of ethnicity, race, and gender.1
Formal diagnostic criteria were established by the Health Consensus Development Conference in 1987. Currently, the diagnosis is made when 2 or more of the following clinical features are present2:
| • | Six or more café au lait macules larger than 0.5 cm before puberty and 1.5 cm after puberty. These hyperpigmented macules with smooth margins typically appear between birth and 2 years of age. Their number and size are not related to disease severity and they do not undergo malignant transformation. |
| • | Skin-fold freckling. This is commonly seen in axillary (C) or inguinal areas (Crowe sign) but can also be seen around the neck, under the breast, and above the eyelids. It typically presents between 3 and 5 years of age. |
| • | Two or more Lisch nodules. These are melanocytic and are present in about 15% of children, typically appearing between 5 and 10 years of age. They should be distinguished from iris nevi by an ophthalmologist using a slit lamp. |
| • | Optic gliomas. These develop in about 15% of children, typically between ages 3 and 5 years. They are usually benign but may cause visual loss, proptosis, or precocious puberty. MRI should be done for visual or endocrine signs or symptoms. |
| • | Two or more neurofibromas or 1 or more plexiform neurofibromas. Plexiform neurofibromas are usually present at birth, whereas dermal neurofibromas usually develop in early adolescence. These benign Schwann cell tumors arise from fibrous tissue around peripheral nerve sheaths and develop in about 30% of patients; they are typically noted at birth but may continue to appear into early adult years. They arise from nerve fascicles and tend to grow along the nerve length; they may cause severe disfigurement. |
| • | Distinctive bony lesion. Sphenoid wing dysplasia usually consists of asymptomatic unilateral defects of the orbital plate and frontal bone, sometimes causing pulsatile enophthalmos. Long bone dysplasia commonly presents in infancy as anterolateral bowing of the legs and repeated fracture caused by cortical thinning. Failure to heal causes pseudoarthrosis. |
| • | A first-degree relative with diagnosed neurofibromatosis type I. |
Neurocognitive deficits, including gross and fine motor delays, visuospatial and language disorders, attention-deficit/hyperactivity disorder, autism spectrum disorder, and behavior and psychosocial issues, are very common in patients with neurofibromatosis type I. All children with neurofibromatosis type I should have a developmental and neuropsychological assessment before school entry for educational planning.
Associated cardiovascular issues include congenital heart disease, vasculopathy (renal artery stenosis, coronary heart disease, cerebrovascular disease, arteriovenous malformations), and hypertension. Annual blood pressure screening and cardiovascular examination are recommended.
Scoliosis is present in 10% to 25% of patients and, depending on severity, may be treated by braces, corrective surgery, or early spinal fusion.3 Short stature is seen in about 15% of patients.4
Consultation with cardiac, orthopedic, and ophthalmological specialists may be indicated to rule out or manage conditions associated with neurofibromatosis.
This patient was enrolled in a behavior modification program. He was also placed in the individualized education program at school for children with learning disabilities. At last checkup, he was making good progress.