Autosomal recessive Neurofibromatosis is an inherited disorder It is of two types: ? Neurofibromatosis - Neurofibromatois II Genetics of Neurofibromatosis Both the neurofibromas are inherited in an autosomal dominant pattern. The genes for them are located on different chromosome - NF-1--) Neurofibrin gene on chromosome 17 - NF-2 --) Merlin gene on chromosome 22 NEUROFIBROMATOSIS TYPE I ? Neurofibromatosis is a comparatively common hereditary disorder in which the skin, nevous system, bone, endocrine glands and sometimes other organs are at the sites of a variety of congenital abnormalities often taking the fonn of benign tumours. . The main feature of neurofibromatosis I is - (i) Spots of hyperpigmentation and (ii) Cutaneous and subcutaneous neurofibromatous tumours'. Hyperpigmentation in Neurofibromatosis I takes two forms :? a) Cafe - au - lait spots' . These are patches of pigmentation and they appear sholy after bih' and occur anywhere on the body. . They are light brown in colour (cafe - au - lait) and do not change in number as the patient ages but they increase in size during pubey. . Presence of more than six cafe - au - lait spots > 1.5 cm in size is considered diagnostic of Neurofibromatosis. b) Freckles' . Neurofibromatosis I is also characterized by the presence of Freckles like or diffuse pigmentation of the axillae and other interiginous areas (groin, under breast) and small round whitish spots. When coupled with cafe au lait patches they are viually pathogtzomonice of the disease. ii) Neurofibromas a) Cutaneous tumours . They are situated in the dermis and form discrete soft or, firm papules. . They are ,flesh coloured or violaceous and often topped with comedo. When pressed, the soft tumours tend to invaginate through a small opening in the skin giving the feeling of a seedless raisin or a scrotum without a testicle. This phenomenon is spoken of as "button holding". b) Subcutaneous tumours . They take two forms ? a) Firm discrete nodules attached to a nerve. b) Plexiform neuromase (overgrowth of subcutaneous tissue sometimes reaching enormous size and occur most often in the face, scalp, neck and chest and may cause hideous disfigurement). Lisch Nodule'? This is another unique .finding of neurofibromatosiso. . It is a small whitish spote present in the iris. Tumours associated with Neurofibromatosis I are 1) Tumours of the CNS a) Optic Nerve Gliomao b) Non-optic Gliomas (usually low grade astrocytomas) c) Nonneoplastic ' hamaomatous" lesion Osborn writes - "The common CNS tumor in NF-1 is optic nerve glioma occuring in 5 to 15% of casese" 2) Other tumours associated with NF-1 a) Pheochromocytoma b) Rhabdomyosarcoma c) leukemia (myeloid leukemia) d) Wilms tumour e) Juvenile Xanthogranuloma