Most newborns with the NF1 gene mutation show few or no signs of the disorder. Café-au-lait spots often initially appear in the first few weeks of life, but their absence in a newborn at risk of inheriting NF1 is not a good indicator of whether or not the child has the disorder, as the spots may appear later.

Other complications that may appear during this period include:

• Plexiform neurofibromas. Neurofibromas are uncommon in infancy. However, another type of neurofibroma – called a plexiform neurofibroma – often first appears in infancy as a soft swelling under the skin. These types of neurofibromas, which affect 50% of people with NF1, are tumors that often involve multiple branches of large nerves. Some plexiform neurofibromas are visible on the surface of the skin early in life, whereas others are located deep inside the body and only are noticed if they cause symptoms later in life. Because the tentacle-like structure of plexiform neurofibromas stretches deep into tissues and nerves, surgical removal of these tumors can be complex. In some cases, surgical resection of plexiform neurofibromas is not possible. Research is underway in the hope of developing new treatments.
• Tibial dysplasia. Although NF1 is not usually associated with congenital malformations, tibial dysplasia is one of two types of bone deformities related to the disorder. While the deformity is rare, when it does occur it is almost always present at birth and visible in the first year of life. Tibial dysplasia involves excessive bowing or curvature of the tibia (also called the shin bone). If tibial dysplasia is suspected and confirmed through an X-ray, a child should be referred to an orthopedist for care focused on the prevention and management of fractures.
• Orbital dysplasia. This is the second of the two major types of bone deformities related to NF1. Orbital dysplasia is a deformity in the orbit – the bony wall around the eye – and/or the sphenoid, which is the bone located behind it. The deformity can result in a bulging, recessing, and/or downward displacement of the eye. Also, a plexiform neurofibroma can grow within the orbit, resulting in an enlargement of the upper eyelid and sometimes the face. An X-ray or CT scan can confirm the presence of orbital dysplasia, and an MRI can detect a plexiform neurofibroma. Medical treatment of deformities of the orbit or sphenoid bone is rarely necessary. However, plastic surgery can often improve cosmetic abnormalities often associated with orbital dysplasia.

During this period, plexiform neurofibromas may emerge or grow, skin-fold freckles may appear in the armpits or groin, and some small neurofibromas may appear on the skin. These neurofibromas are soft to the touch, painless, and usually appear as small, pink or purple bumps on the skin. Most young children rarely have more than a few small skin neurofibromas.

Additional complications during this developmental period could include:

• Short stature and larger-than-average head size. These two abnormalities of growth are commonly noticed during the preschool years. Children with NF1 are often shorter that would be expected for their family, although the cause of this short stature is unknown. The larger-than-average head size – called macrocephaly – does not cause discomfort or neurological problems. In rare cases, macrocephaly may be due to hydrocephalus, which is an increased pressure of fluid inside the brain. Symptoms of hydrocephalus include headache and vomiting, although a diagnosis can only be confirmed with a CT or MRI scan.
• Optic glioma. This tumor of the optic nerve (nerve from the eye to the brain) emerges in early childhood in about 15% of children with NF1. This tumor sometimes causes bulging of the eye and/or loss of vision and can also affect hormone secretion in the pituitary gland that may lead to the early onset of puberty. These types of optic gliomas are diagnosed by mean of MRI scans and are usually responsive to chemotherapy. Sometimes an MRI scan might reveal a thickening of the optic nerve in a child with NF1 who has no outward signs or symptoms of optic glioma. These cases only rarely progress to a point requiring treatment. All children with NF1 should have annual, comprehensive eye exams to insure early diagnosis of optic glioma.

Some of the physical features of NF1 outlined earlier could begin or continue to appear through the school-age years. For example, skin-fold freckles may increase, plexifom neurofibromas may grow, and neurofibromas may become visible on the skin. Also tan bumps on the colored part of the eye – called iris Lisch nodules – may appear. These bumps are harmless and do not interfere with vision.

• Learning disabilities. At least 50% of children with NF1 have some form of learning disability. Because the school-age years mark the beginning of a child’s formal education, this is often the first time that a child’s learning disability becomes apparent. The specific form and severity of learning disability varies among children and can involve any combination of visual, spatial, speech, language, reading, and math skills. The management of learning disabilities in children with NF1 is the same as for other children with learning disabilities. In cooperation with the child’s school, a thorough assessment of the child’s skills and areas of weakness should be performed to develop an individualized education program (IEP) designed to meet the child’s special needs.
• Attention-deficit-hyperactivity disorder (ADHD). About 30% of children with NF1 also have ADHD, a childhood disorder than can continue through adolescence and adulthood. Symptoms of ADHD include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity. Treatment for ADHD, which focuses on reducing symptoms and improving functioning, often includes a combination of stimulant medications and behavioral therapy.

Adolescence is generally a time of change – including changes in the manifestations of NF1. For example, children who have not yet developed neurofibromas on their skin may begin to experience skin neurofibromas during puberty. Also, skin freckling may increase.

While the cause of these changes is not well understood, it is believed that changes in hormones may be responsible. Hormonal changes may also be related to the appearance of increased growth of neurofibromas that is experienced by many women with NF1 during pregnancy.

• Vascular problems
  • High blood pressure (hypertension) - In some people with NF1, a problem call renal artery stenosis (blockage of the artery to the kidney) can cause hypertension. In rare cases, a tumor of the adrenal gland called pheochromocytoma may cause severe high blood pressure and require surgery. It’s important that blood pressure checks be included in routine physical exams for NF1 patients.
  Moyamoya disease - This is a rare vascular disorder that causes blood vessels in the brain to progressively narrow, causing blood flow to be reduced and increasing the risk of stroke.
• Scoliosis – This condition is a lateral curvature of the spine. Common in people with NF1, scoliosis usually appears in early childhood. Treatment includes periodic spine X-rays and physical examination to determine if corrective measures are needed. A brace is used in some cases to prevent progression of the problem and some progress to the point of requiring surgery.
• Malignant peripheral nerve sheath tumor (MPNST) – This is a rare malignant tumor that can sometimes develop from a plexiform neurofibroma. Signs include persistent severe pain, sudden growth of a neurofibroma, or a change from a tumor that has been soft to the touch to one that is hard. Diagnosis usually requires imaging, in some cases use of a radioactive tracer (PET scan), and eventually surgery to biopsy the tumor. MPNST affects about 10% of individuals with NF1. Treatment typically includes surgery, chemotherapy, and radiation.