The following is a list of conditions and complications associated with NF-1, and, where available, age range of onset and progressive development, occurrence percentage of NF-1 population, method of earliest diagnosis, and treatments and related medical specialties. The progression of the condition is roughly as follows: # Congenital musculoskeletal disorders may or may not be present # Cutaneous conditions may be observed in early infancy # Small tumors may arise in the retina which can eventually lead to blindness. Also, Lisch Nodules may grow on the iris, but these are harmless. # Learning disabilities may arise in preschool children # Neurofibromas may occur and can sometimes cause many dependent neurological conditions and cutaneous and skeletal disfigurement. # Depression and social anxiety may occur as a result of disabilities caused by the condition # Neurofibromas may, in 8-13% of cases, transition into cancer, which can be fatal The NF Clinical Program at St. Louis Children's Hospital maintains a comprehensive list of current NF research studies. Musculoskeletal disorder Musculoskeletal abnormalities affecting the skull include sphenoid bone dysplasia, congenital hydrocephalus and associated neurologic impairment. These abnormalities are non-progressive and may be diagnosed in the fetus or at birth. Disorders affecting the spine include: * In NF-1, there can be a generalized abnormality of the soft tissues in the fetus, which is referred to as mesodermal dysplasia, resulting in maldevelopment of skeletal structures. * Meningoceles and formation of cystic diverticula of the dura of the spine, unrelated to Spina bifida * Radiographically, dural ectasia can lead to scalloping of the posterior vertebral bodies and to the formation of cystic diverticula of the dura of the spine. This may result in temporary or permanent loss of lower extremity sensorimotor function. * Focal scoliosis and/or kyphosis are the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately 25% of patients will require corrective surgery. Skeletal muscle weakness and motor control deficits Deficits in motor function in NF-1 have been long recognised and have been historically attributed to nerve dysfunction. In recent years however, studies suggest NF-1 is associated with a primary problem in muscle function (myopathy). Clinical findings in people with NF-1 include: * Reduced skeletal muscle size * Reduced exercise capacity * Muscle weakness (The most recent study reports between 30–50% reduced upper and lower limb muscle strength in NF-1 children compare with matched controls). Studies in genetically modified mice have thus far confirmed that the NF1 gene is vital for normal muscle development and metabolism. Knockout of the NF1 gene in muscle results in deregulated lipid metabolism and muscle weakness. NF-1 is a disease in the RASopathy family of diseases, which include Costello Syndrome, Noonan Syndrome, and Cardiofaciocutaneous syndrome. The RASopathies also present with skeletal muscle weakness. It is likely that impaired muscle function in these disorders is linked to altered Ras/MAPK signalling, however, the precise molecular mechanisms remain unknown. Facial bones and limbs * Bowing of a long bone with a tendency to fracture and not heal, yielding a pseudarthrosis. The most common bone to be affected is the tibia, causing congenital pseudarthrosis of the tibia or CPT. CPT occurs in 2–4% of individuals with NF-1. Treatment includes limb amputation or correction by Ilizarov method as a limb-sparing technique. * Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia) * Unilateral overgrowth of a limb. When a plexiform neurofibroma manifests on a leg or arm, it will cause extra blood circulation, and may thus accelerate the growth of the limb. This may cause considerable difference in length between left and right limbs. To equalize the difference during childhood, there is an orthopedic surgery called epiphysiodesis, where growth at the epiphyseal (growth) plate is halted. It can be performed on one side of the bone to help correct an angular deformity, or on both sides to stop growth of that bone completely. The surgery must also be carefully planned with regard to timing, as it is non-reversible. The goal is that the limbs are at near-equal length at end of growth... Skin * Flat pigmented lesions of the skin called café au lait spots, are hyper pigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means "coffee with milk". The borders may be smooth or irregular. These spots can grow from birth and can continue to grow throughout the person's lifetime. They can increase in size and numbers during puberty and during pregnancies. They are present in about 99% patient of European origin and in about 93% patient of Indian origin. * Freckling of the axillae or inguinal regions. * Dermal neurofibroma, manifested as single or multiple firm, rubbery bumps of varying sizes on a person's skin. Age of onset is puberty. Progressive in number and size. Not malignant. Can be treated with CO2 lasers or by removal by a plastic surgeon specialized in NF1. Eye disease * Lisch nodules in the iris. * Optic nerve gliomas along one or both optic nerves or the optic chiasm can cause bulging of the eyes, involuntary eye movement, squinting, and / or vision loss. Treatment may include surgery, radiation +/- steroids, or chemotherapy (in children). Neurobehavioral developmental disorder The most common complication in patients with NF-1 is cognitive and learning disability. These cognitive problems have been shown to be present in approximately 90% of children and adults with NF-1 and have significant effects on their schooling and everyday life. These cognitive problems have been shown to be stable into adulthood mainly in the mid 20s to early 30s and do not get worse unlike some of the other physical symptoms of NF-1. The most common cognitive problems are with perception, executive functioning and attention. Disorders include: * Approximately 42% of children with NF-1 have symptoms of autism, with 36.78% of them being severe cases, 33.33% being mild to moderate cases, and 29.89% of them having both symptoms of autism and ADHD. * Attention deficit hyperactivity disorder has been shown to be present in approximately 40% of children with NF-1. * Speech and language delays have also been identified in approximately 68% of preschool children with NF-1. * Motor deficits are common. Motor deficits due to NF-1 are probably not cerebellar. * Spatial deficit. Lovastatin, normally used to treat hypercholesterolemia, is currently in phase one of clinical trial (NCT00352599). This drug has been shown to reverse spatial deficits in mice. Simvastatin, a drug similar to lovastatin, did not show benefit on cognitive function or behaviour in two randomized controlled trials in children with NF-1. Nervous system disease The primary neurologic involvement in NF-1 is of the peripheral nervous system, and secondarily of the central nervous system. Schwannomatosis is a rare condition defined by the presence of multiple benign tumors of nerves that are frequently very painful. In addition to pain, weakness is a common problem. Symptoms usually begin in young or mid-adult years. Peripheral neuropathy Neurofibroma A neurofibroma is a lesion of the peripheral nervous system. Its cellular lineage is uncertain, and may derive from Schwann cells, other perineural cell lines, or fibroblasts. Neurofibromas may arise sporadically, or in association with NF-1. A neurofibroma may arise at any point along a peripheral nerve. A number of drugs have been studied to treat this condition. Neurofibroma conditions are progressive and include: * Plexiform neurofibroma: Often congenital. Lesions are composed of sheets of neurofibromatous tissue that may infiltrate and encase major nerves, blood vessels, and other vital structures. These lesions are difficult and sometimes impossible to routinely resect without causing any significant damage to surrounding nerves and tissue. However, early intervention may be beneficial: a 2004 study in Germany concluded "Early surgical intervention of small superficial PNFs is uncomplicated, without burden for even the youngsters and enables total resection of the tumors. It may be considered as a preventive strategy for later disfigurement and functional deficits." * Solitary neurofibroma, affecting 8–12% of patients with NF-1. This occurs in a deep nerve trunk. Diagnosis by cross-sectional imaging (e.g., computed tomography or magnetic resonance) as a fusiform enlargement of a nerve. * Schwannomas, peripheral nerve-sheath tumors which are seen with increased frequency in NF-1. The major distinction between a schwannoma and a solitary neurofibroma is that a schwannoma can be resected while sparing the underlying nerve, whereas resection of a neurofibroma requires the sacrifice of the underlying nerve. * Nerve root neurofibroma. * Bones, especially the ribs, can develop chronic erosions (pits) from the constant pressure of adjacent neurofibroma or Schwannoma. Similarly, the neural foramen of the spine can be widened due to the presence of a nerve root neurofibroma or schwannoma. Surgery may be needed when NF-1 related tumors compress organs or other structures. Nerve sheath tumor MRI image showing malignant peripheral nerve sheath tumor in the left tibia in<unk> <unk> 1 * Chronic pain, numbness, and/or paralysis due to peripheral nerve sheath tumor. Other complications * Renal artery anomalies or pheochromocytoma and associated chronic hypertension
types of Neurofibromatosis
symptom of Neurofibromatosis
symptom of Lesch–Nyhan syndrome
symptom of Kabuki syndrome
symptom of Tay–Sachs disease
symptom of Laron syndrome
symptoms of Jervell and Lange-Nielsen syndrome
complications of Xeroderma pigmentosum