N eurofibromatoses (NFs) are a group of diseases involving the skin as well as other organs. At least 8 different forms of NFs have been described; these are often referred to as neurofibromatosis 1 through 8 or (NF1-8). However, there is no unified classification system for these diseases. NF1 and NF2 are well-described forms, defined by clinical features as well as distinct genetic mutations. With an incidence of about 1 in 2,500 to 3,300, NF1 or von Recklinghausen’s disease, is the most common neurocutaneous disease. It accounts for up to 90% of the cases of NF. NF1 is one of the most common autosomal dominant disorders in humans, with a spontaneous mutation rate of about 60%. The diagnosis is based on an individual demonstrating at least two of seven clinical criteria as defined by the National Institute of Health Consensus Development Con-ference on Neurofibromatosis. The NF1 gene on chromosome 17 (17q11.2) encodes for a large protein called neurofibromin. Mutations in this tumor suppressor gene result in the production of a nonfunctional neurofibromin protein, or the absence of its expression altogether. Neuro-fibromin functions primarily as a RAS negative regulator, suggesting that targeted therapy for NF1 might derive from inhibition of the RAS signaling pathway. Case #1 This 50-year-old patient presented with these lesions on the trunk, which she has had since her late childhood. What is your diagnosis? __________________________ 1. These lesions are exclusively found in patients with NF1. T____ F____ 2. These lesions are only found on the skin. T____ F____ 3. The diagnosis of NF1 can’t be made without the presence of these lesions. T____ F____ 4. When these lesions are found around the areola or the nipple (Bacardi sign), they are virtually diagnostic for NF1 in women. T____ F____ 5. Malignant degeneration of these lesions occurs in 30% to 50% of patients with NF1. T____ F____ Case #2 Another 50-year-old patient presented with nodules on the trunk as well as several pigmented lesions similar to the one seen on the left lower part of this photo. What is your diagnosis? __________________________ 1. These lesions are often the first cutaneous manifestation of NF1. T____ F____ 2. The diagnosis of NF1 can be made if a total of five lesions measuring more than 15 mm are found in this patient. T____ F____ 3. These lesions usually grow in size and number during the first 10 years of life. T____ F____ 4. These lesions may gradually fade with age. T____ F____ 5. Histologic features include melanocytes in Indian file arrangement between collagen bundles extending to the lower two-thirds of the dermis with presence of melanocytes around nerves, vessels and adnexae. T____ F____ Case #3 Examination of the axillae of the patient presented in case #2 showed this finding. What is your diagnosis? __________________________ 1. In the absence of similar changes in the inguinal area, this finding should not be considered a clinical diagnostic criterion for NF1. T____ F____ 2. This clinical finding is usually present at birth. T____ F____ 3. Only 30% of children with NF1 will have these changes before age 6. T____ F____ 4. An alternative name for this finding is Fox-Fordyce disease. T____ F____ 5. This finding is due to follicular keratinization with resultant plugging of the apocrine ducts and secondary bacterial infection. T____ F____ Useful Sources 1. Lynch TM, Gutmann DH. Neurofibromatosis 1. Neurol Clin 2002 Aug;20(3):841-65. 2. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997;278:51-57. Diagnosing Neurofibromatosis The National Institute of Health Consensus Development Conference on neurofibromatosis (1987) determined the criteria for the diagnosis of neurofibromatosis type 1 as: 1. Six or more café-au-lait spots that are greater than 1.5 cm in postpubertal individuals or 0.5 cm or larger in prepubertal individuals. 2. At least two neurofibromas of any type or at least one plexiform neurofibroma. 3. Freckling in the axilla or groin (Crowe’s sign). 4. Optic glioma. 5. At least two Lisch nodules (benign iris hamartomas). 6. A distinct bony lesion including sphenoid wing dysplasia or thinning of the long bone cortex. 7. A first-degree relative with NF1. *Fulfilling at least two of seven criteria makes a diagnosis of NF1.
Neurocutaneous Disorders Part II: A Self-Assessment Quiz
N eurofibromatoses (NFs) are a group of diseases involving the skin as well as other organs. At least 8 different forms of NFs have been described; these are often referred to as neurofibromatosis 1 through 8 or (NF1-8). However, there is no unified classification system for these diseases. NF1 and NF2 are well-described forms, defined by clinical features as well as distinct genetic mutations. With an incidence of about 1 in 2,500 to 3,300, NF1 or von Recklinghausen’s disease, is the most common neurocutaneous disease. It accounts for up to 90% of the cases of NF. NF1 is one of the most common autosomal dominant disorders in humans, with a spontaneous mutation rate of about 60%. The diagnosis is based on an individual demonstrating at least two of seven clinical criteria as defined by the National Institute of Health Consensus Development Con-ference on Neurofibromatosis. The NF1 gene on chromosome 17 (17q11.2) encodes for a large protein called neurofibromin. Mutations in this tumor suppressor gene result in the production of a nonfunctional neurofibromin protein, or the absence of its expression altogether. Neuro-fibromin functions primarily as a RAS negative regulator, suggesting that targeted therapy for NF1 might derive from inhibition of the RAS signaling pathway. Case #1 This 50-year-old patient presented with these lesions on the trunk, which she has had since her late childhood. What is your diagnosis? __________________________ 1. These lesions are exclusively found in patients with NF1. T____ F____ 2. These lesions are only found on the skin. T____ F____ 3. The diagnosis of NF1 can’t be made without the presence of these lesions. T____ F____ 4. When these lesions are found around the areola or the nipple (Bacardi sign), they are virtually diagnostic for NF1 in women. T____ F____ 5. Malignant degeneration of these lesions occurs in 30% to 50% of patients with NF1. T____ F____ Case #2 Another 50-year-old patient presented with nodules on the trunk as well as several pigmented lesions similar to the one seen on the left lower part of this photo. What is your diagnosis? __________________________ 1. These lesions are often the first cutaneous manifestation of NF1. T____ F____ 2. The diagnosis of NF1 can be made if a total of five lesions measuring more than 15 mm are found in this patient. T____ F____ 3. These lesions usually grow in size and number during the first 10 years of life. T____ F____ 4. These lesions may gradually fade with age. T____ F____ 5. Histologic features include melanocytes in Indian file arrangement between collagen bundles extending to the lower two-thirds of the dermis with presence of melanocytes around nerves, vessels and adnexae. T____ F____ Case #3 Examination of the axillae of the patient presented in case #2 showed this finding. What is your diagnosis? __________________________ 1. In the absence of similar changes in the inguinal area, this finding should not be considered a clinical diagnostic criterion for NF1. T____ F____ 2. This clinical finding is usually present at birth. T____ F____ 3. Only 30% of children with NF1 will have these changes before age 6. T____ F____ 4. An alternative name for this finding is Fox-Fordyce disease. T____ F____ 5. This finding is due to follicular keratinization with resultant plugging of the apocrine ducts and secondary bacterial infection. T____ F____ Useful Sources 1. Lynch TM, Gutmann DH. Neurofibromatosis 1. Neurol Clin 2002 Aug;20(3):841-65. 2. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997;278:51-57. Diagnosing Neurofibromatosis The National Institute of Health Consensus Development Conference on neurofibromatosis (1987) determined the criteria for the diagnosis of neurofibromatosis type 1 as: 1. Six or more café-au-lait spots that are greater than 1.5 cm in postpubertal individuals or 0.5 cm or larger in prepubertal individuals. 2. At least two neurofibromas of any type or at least one plexiform neurofibroma. 3. Freckling in the axilla or groin (Crowe’s sign). 4. Optic glioma. 5. At least two Lisch nodules (benign iris hamartomas). 6. A distinct bony lesion including sphenoid wing dysplasia or thinning of the long bone cortex. 7. A first-degree relative with NF1. *Fulfilling at least two of seven criteria makes a diagnosis of NF1.
N eurofibromatoses (NFs) are a group of diseases involving the skin as well as other organs. At least 8 different forms of NFs have been described; these are often referred to as neurofibromatosis 1 through 8 or (NF1-8). However, there is no unified classification system for these diseases. NF1 and NF2 are well-described forms, defined by clinical features as well as distinct genetic mutations. With an incidence of about 1 in 2,500 to 3,300, NF1 or von Recklinghausen’s disease, is the most common neurocutaneous disease. It accounts for up to 90% of the cases of NF. NF1 is one of the most common autosomal dominant disorders in humans, with a spontaneous mutation rate of about 60%. The diagnosis is based on an individual demonstrating at least two of seven clinical criteria as defined by the National Institute of Health Consensus Development Con-ference on Neurofibromatosis. The NF1 gene on chromosome 17 (17q11.2) encodes for a large protein called neurofibromin. Mutations in this tumor suppressor gene result in the production of a nonfunctional neurofibromin protein, or the absence of its expression altogether. Neuro-fibromin functions primarily as a RAS negative regulator, suggesting that targeted therapy for NF1 might derive from inhibition of the RAS signaling pathway. Case #1 This 50-year-old patient presented with these lesions on the trunk, which she has had since her late childhood. What is your diagnosis? __________________________ 1. These lesions are exclusively found in patients with NF1. T____ F____ 2. These lesions are only found on the skin. T____ F____ 3. The diagnosis of NF1 can’t be made without the presence of these lesions. T____ F____ 4. When these lesions are found around the areola or the nipple (Bacardi sign), they are virtually diagnostic for NF1 in women. T____ F____ 5. Malignant degeneration of these lesions occurs in 30% to 50% of patients with NF1. T____ F____ Case #2 Another 50-year-old patient presented with nodules on the trunk as well as several pigmented lesions similar to the one seen on the left lower part of this photo. What is your diagnosis? __________________________ 1. These lesions are often the first cutaneous manifestation of NF1. T____ F____ 2. The diagnosis of NF1 can be made if a total of five lesions measuring more than 15 mm are found in this patient. T____ F____ 3. These lesions usually grow in size and number during the first 10 years of life. T____ F____ 4. These lesions may gradually fade with age. T____ F____ 5. Histologic features include melanocytes in Indian file arrangement between collagen bundles extending to the lower two-thirds of the dermis with presence of melanocytes around nerves, vessels and adnexae. T____ F____ Case #3 Examination of the axillae of the patient presented in case #2 showed this finding. What is your diagnosis? __________________________ 1. In the absence of similar changes in the inguinal area, this finding should not be considered a clinical diagnostic criterion for NF1. T____ F____ 2. This clinical finding is usually present at birth. T____ F____ 3. Only 30% of children with NF1 will have these changes before age 6. T____ F____ 4. An alternative name for this finding is Fox-Fordyce disease. T____ F____ 5. This finding is due to follicular keratinization with resultant plugging of the apocrine ducts and secondary bacterial infection. T____ F____ Useful Sources 1. Lynch TM, Gutmann DH. Neurofibromatosis 1. Neurol Clin 2002 Aug;20(3):841-65. 2. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997;278:51-57. Diagnosing Neurofibromatosis The National Institute of Health Consensus Development Conference on neurofibromatosis (1987) determined the criteria for the diagnosis of neurofibromatosis type 1 as: 1. Six or more café-au-lait spots that are greater than 1.5 cm in postpubertal individuals or 0.5 cm or larger in prepubertal individuals. 2. At least two neurofibromas of any type or at least one plexiform neurofibroma. 3. Freckling in the axilla or groin (Crowe’s sign). 4. Optic glioma. 5. At least two Lisch nodules (benign iris hamartomas). 6. A distinct bony lesion including sphenoid wing dysplasia or thinning of the long bone cortex. 7. A first-degree relative with NF1. *Fulfilling at least two of seven criteria makes a diagnosis of NF1.
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