Plexiform neurofibromatosis - Essay Example

Sathya Prakash Manimunda Manimunda 22 June 2008 Plexiform Neurofibromatosis Neurocutaneous disorders are diseases that involve nervous system, skin, and retina and other ectodermal tissues. They are congenital. Migration of neural cells to brain and melanoblasts to the skin from the neural crest occurs between 3 to 6 months of intrauterine life. A disturbance of this migration results in neurocutaneous syndromes involving ectodermal and neuroectodermal elements (Panda 526). Neurofibromatosis is an autosomal dominant neurogenetic disorder. It can present with spectrum of symptomatology, it affects bone, nervous system, soft tissue and the skin. There are two varieties of neurofibromatosis, NF-1, popularly known as peripheral neurofibromatosis and NF-2, also known as central neurofibromatosis. A third variant is known as segmental neurofibromatosis. However, NF-1 has often central features. Here, the discussion will be limited to NF-1 which can present as plexiform neurofibromatosis. Increased nerve growth stimulating activity is incriminated for the development of neurofibromatosis. The disease has a genetic basis. NF-1 is linked to a large gene on band 17q 11.2. It encodes a protein termed neurofibromin. The protein has been found essential for the negative regulation of Ras, suggesting that neurofibromin acts as a tumor suppressor. Truncations in neurofibromin led to the mutations in most of the NF-1 cases. NF-1 is a disorder with variable phenotypic expression. Some patients may have only cutaneous expression, while others may have life threatening and disfiguring complications. These variations are demonstrated even with in the families. The disease also tends to change and develop with time. Many different mutations with in neurofibromatosis gene have been described. Spontaneous Manimunda mutations are thought to contribute to approximately 30-50% of neurofibromatosis cases. The world wide prevalence of this disease is 1 in 2500 to 3300 live births. All race groups are equally affected and there is no sexual preponderance (Kam and Helm). Most patients with neurofibromatosis present with caf au lait macules during first three years of life. Neurofibromas develop during late adolescence. Few may present with complications like pain caused by neurofibromas, pathological fractures or hypertensive head ache caused by pheochromocytoma. Physical examination may reveal the involvement of different organs and systems. Caf au lait spots are unusual pigmentary patterns, irregularly shaped, evenly pigmented, brown macules. Most individuals with neurofibromatosis have 6 or more spots that are 1.5cm or greater in diameter. In young children, 5 or more caf au lait macules greater than 0.5 cm in diameter are suggestive of neurofibromatosis. 1 or 2 caf au lait macules are encountered even in healthy individuals. Lisch nodules are hamartomas of the iris that appears dome shaped. Slit lamp examination will reveal this and help in confirming the diagnosis of neurofibromatosis. Axillary freckling (as well as inguinal freckling) known as Crowe sign is a useful diagnostic feature in neurofibromatosis. They develop during puberty. Areas of freckling and hypertrichosis occasionally overlay plexiform neurofibromas. Bone involvement can include pseudoarthrosis of tibia, bowing of long bones and orbital defects. Occasionally pulsating exophthalmos is encountered. Neurofibromas are the most common benign tumor of NF-1. These tumors are composed of Schwann cells, fibroblasts, mast cells and vascular component. They can develop at any point along a nerve. Three subtypes of neurofibroma exist. They are cutaneous, subcutaneous and Manimunda plexiform neurofibroma. Plexiform neurofibromas are noncircumscibed, thick, and irregular, and they can cause disfigurement by entwining important supportive structures. The plexiform subtype is specific for NF-1. Various neurological abnormalities like acoustic nerve involvement and deafness, gliomas of the optic nerve, intracranial tumors like astrocytoma, meningioma, intra medullary glioma, and ependymoma are encountered with greater frequency in these patients. Many individuals with neurofibromatosis have below average intelligence. The endocrine abnormalities like short stature, growth hormone deficiency and occasional sexual precocity are seen in patients with neurofibromatosis (NIH consensus statement on neurofibromatosis 575-78). The diagnostic criteria for neurofibromatosis (NF-1) are met if 2 or more of the listed features are present in a suspected case. First, six or more caf au lait macules larger than 5 mm in greatest diameter in prepubertal individuals and those larger than 15 mm in greatest diameter in postpubertal individuals. Second, two or more neurofibromas of any type or 1 plexiform neurofibroma. Third, freckling in the axillary or inguinal regions. Fourth, optic glioma. Fifth, two or more Lisch nodules. Sixth, a distinctive osseous lesion, such as sphenoid dysplasia or thinning of the long bone cortex, with or with out pseudoarthrosis. Seventh and final criteria is, a first degree relative with NF-1 according to the above criteria (Debella, Szudek, and Friedman 608-14). In the management of NF-1, the differential diagnosis, investigations, treatment and interdepartmental co-operation has to be considered. The differential diagnosis include multiple endocrine neoplasia-I, abdominal neurofibromatosis, neurofibromatosis with noonan syndrome, NF-2, and segmental Manimunda neurofibromatosis. The investigations include, mutation analysis if available, plain radiography to know growth disturbance, MRI of the brain and cervical spines to identify the lesions and to confirm the presence of optic glioma if it is suspected. 18 flurodeoxyglucose positron emission tomography may be helpful in determining malignant changes in plexiform neurofibromas in persons with NF-1. The CT will show chest involvement, bony anomalies due to pressure effect, presence of tumors and structural abnormalities of brain. A wood lamp examination to identify the presence of caf au lait spots, slit lamp examination for the presence of lisch nodules and histological examination of axillary and inguinal freckling are other helpful investigations. The treatment of NF-1 is predominantly surgical. When ever there is increase in size and presence of pain, malignant transformation of neurofibroma has to be considered and excision biopsy has to be done. Acoustic neuromas has to be excised with great caution and if there is tumor it has to be removed. A orthopedic physician, plastic surgeon and psychological and psychiatric personnel should be involved in the team to manage neurofibromatosis. Considering the autosomal dominant inheritance pattern of neurofibromatosis, genetic counseling should be included in the treatment of all patients affected with this disease. Regular follow up for physical, ophthalmologic and skeletal abnormalities is warranted. Similarly the blood pressure and the status of neurofibroma for malignant transformation has to be watched regularly. The information about neurofibromatosis help group has to be provided. The patients with NF-1 have an estimated 3-15% additional risk of malignant disease in their lifetime. The prognosis of neurofibromatosis is varied, as is the nature of disease. Manimunda Works Cited Debella, K, Szudek, J, and Friedman, JM. "Use of National Institute of Health Criteria for Diagnosis of Neurofibromatosis 1". Paediatrics. Mar 2000; 105 (3 Pt 1): 608-14. Kam, Jenniffer R, and Helm, Thomas N. "Neurofibromatosis". 06 May 2008. e medicine from WebMD. 22 June 2008. "National Institute of Health Consensus Development Conference, Neurofibromatosis. Conference Statement". Arch Neurol. May 1998; 45 (5): 575- 78. Panda, UN. "Neurology". Current Medical Diagnosis and Treatment. New Delhi: Jaypee Brothers, 2002. 526. Read More