Lethal manifestations of neurofibromatosis type-1 in childhood

Abstract

Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is a relatively common, inherited neurocutaneous disorder. Although 37% of patients with the disease die as a result of it, this is usually considered a late feature. Life threatening complications are infrequent before the age of 30, although deaths from NF-1 do occur in the paediatric age group. The following series demonstrates the clinicopathological features of 4 lethal cases taken from the autopsy files at the ACH during the period 1952 to 1991. All patients had café au lait patches and neurofibromas. Case 1: A 2 year-old female with hypsarrhythmia and mental retardation, died from pneumonia. Autopsy demonstrated diffuse gliosis but no tumours. Case 2: An 11 year-old female with NF-1 and a hypothalamic glioma at age 3. This responded well to radiotherapy until the age of 10 when the patient presented with fitting. This was presumed to be due to vascular insufficiency, as angiography showed occlusion of the R. internal carotid. Gradual deterioration was followed by death 9 months later. At autopsy a cystic astrocytoma of the cerebellum was found in addition to the original hypothalamic glioma. Case 3: A 15 year-old male with NF-1 diagnosed at birth. Severe scoliosis required numerous admissions to hospital. At 2 years of age he was noted to have a mediastinal mass but no action was taken at the time. At age 15 the patient developed severe abdominal pain and ultrasound revealed a large tumour displacing the liver and spleen. The patient died unexpectedly whilst in hospital. Autopsy demonstrated haemorrhage into a plexiform neurofibroma, in association with a malignant schwannoma. Case 4: A 13 year-old male with NF-1 diagnosed at the age of 5. No problems occurred until age 12, when he developed a L. thalamic glioma. There was an initial good response to radiotherapy followed by gradual deterioration. Death occurred and at autopsy he was found to have gliomatosls cerebri. These cases demonstrate that death may occur in childhood due to NF-1 by a variety of mechanisms. Malignancy is a significant risk and was seen in two patients, Including two primary brain tumours in Case 2. Although sudden death is not usually considered an outcome of NF-1, it was found in 1 of the 4 patients. Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is a relatively common, inherited neurocutaneous disorder. Although 37% of patients with the disease die as a result of it, this is usually considered a late feature. Life threatening complications are infrequent before the age of 30, although deaths from NF-1 do occur in the paediatric age group. The following series demonstrates the clinicopathological features of 4 lethal cases taken from the autopsy files at the ACH during the period 1952 to 1991. All patients had café au lait patches and neurofibromas. Case 1: A 2 year-old female with hypsarrhythmia and mental retardation, died from pneumonia. Autopsy demonstrated diffuse gliosis but no tumours. Case 2: An 11 year-old female with NF-1 and a hypothalamic glioma at age 3. This responded well to radiotherapy until the age of 10 when the patient presented with fitting. This was presumed to be due to vascular insufficiency, as angiography showed occlusion of the R. internal carotid. Gradual deterioration was followed by death 9 months later. At autopsy a cystic astrocytoma of the cerebellum was found in addition to the original hypothalamic glioma. Case 3: A 15 year-old male with NF-1 diagnosed at birth. Severe scoliosis required numerous admissions to hospital. At 2 years of age he was noted to have a mediastinal mass but no action was taken at the time. At age 15 the patient developed severe abdominal pain and ultrasound revealed a large tumour displacing the liver and spleen. The patient died unexpectedly whilst in hospital. Autopsy demonstrated haemorrhage into a plexiform neurofibroma, in association with a malignant schwannoma. Case 4: A 13 year-old male with NF-1 diagnosed at the age of 5. No problems occurred until age 12, when he developed a L. thalamic glioma. There was an initial good response to radiotherapy followed by gradual deterioration. Death occurred and at autopsy he was found to have gliomatosls cerebri. These cases demonstrate that death may occur in childhood due to NF-1 by a variety of mechanisms. Malignancy is a significant risk and was seen in two patients, Including two primary brain tumours in Case 2. Although sudden death is not usually considered an outcome of NF-1, it was found in 1 of the 4 patients.