Optic gliomas in children with neurofibromatosis type 1

Over a 24-year period, optic gliomas were found in 29 children, 16 of whom had neurofibromatosis type 1 (NF-1). These 16 children comprised 21% of all children referred for management of NF-1 and its complications. The finding of optic glioma led to the diagnosis of NF-1 in 4 children. The mean age at diagnosis of optic glioma in NF-1 children was 6.4 years, and the average estimated duration of visual symptoms prior to diagnosis was 2.1 years. Most optic gliomas in NF-1 children were ascertained because of a visual complaint (69%), and an even greater number of children (88%) had an abnormal ophthalmological examination. The optic chiasm was involved in 75% of the patients. All of the seven children with optic glioma examined by visual evoked potential had an abnormal response ipsilateral to the tumour. The majority of the children received radiation therapy. After a mean follow up period of 5.8 years no deaths had occurred due to optic glioma, but in 35% of the children vision was worse. We conclude that optic glioma is a common, serious complication in NF-1 children. Routine care of such patients should include regular noninvasive investigations aimed at detecting lesions of the optic pathway.The results were presented in part at the meeting of the Society for Pediatric Research, Washington, D. C., May 1989     

Multiple coronary artery aneurysms in a child with neurofibromatosis type 1

A number of frequently unrecognised vascular manifestations have been described in patients with neurofibromatosis type 1 (NF1), including involvement of the great vessels, cerebral, visceral and renal arteries. Rarely, changes in the coronary arteries have been reported in adults with NF1. We report on a 16-year-old boy affected by NF1 with dysmorphic features and three aneurysms in the mid-portion of the left descending coronary artery disclosed by chance during investigation for a malignant peripheral nerve sheath tumour. Molecular analysis detected a gross de novo deletion in the NF1 gene. The boy had had no previous cardiac symptoms but died suddenly after developing signs and symptoms suggestive of myocardial infarction. Conclusion To the best of our knowledge, this represents the first report of multiple lesions in the coronary arteries in a child affected by neurofibromatosis type 1 with a known deletion of the neurofibromatosis type 1 gene. Received: 11 November 1999 and in revised form: 9 January 2000 / Accepted: 9 January 2000     

Quality of life and psychological adjustment in children and adolescents with neurofibromatosis type 1

OBJECTIVE: To assess quality of life (QoL) and psychological adjustment in children and adolescents with neurofibromatosis type 1 (NF1). STUDY DESIGN: Forty-six patients with NF1 were investigated between the ages of 7 and 16 years (mean, 11.6 years), with children and parents used as informants. TNO-AZL Questionnaire for Children's Health-Related Quality of Life and Child Behavior Checklist scores were compared with healthy reference groups. Predictive values of sociodemographic variables, illness-related variables, and family-related variables for quality of life and psychological adjustment were assessed. RESULTS: Most dimensions of QoL in NF1 children and adolescents were different from reference values. Deviations in the NF1 group were an impairment of motor, cognitive, and social functioning and a reduction of positive and negative emotions. Also, psychological adjustment in patients with NF1 was significantly impaired compared with normal subjects. Illness-related variables had a negative impact on the emotional domain of QoL. Good family relationships positively affected both QoL and psychological adjustment. CONCLUSIONS: QoL and psychological adjustment are impaired in children and adolescents with NF1. Illness-related variables and the quality of family relationships are important predictors.     

Unidentified bright objects on brain MRI in children as a diagnostic criterion for neurofibromatosis type 1

Background Lesions of the brain denominated as unidentified bright objects (UBOs), which are not included in the diagnostic criteria for neurofibromatosis type 1 (NF1) established by the National Institutes of Health (NIH), have been detected by MRI. Objective The purpose of this study was to investigate the possibility of including the presence of UBOs as a diagnostic criterion for NF1 in children. Materials and methods The study included 88 children between the ages of 2 and 18 years. The case group consisted of 40 children diagnosed with sporadic or familial NF1 according to the criteria established by the NIH. A control group consisted of 48 individuals referred for routine MRI of the brain for other complaints not related to NF1. Results UBOs were identified in 70% of the NF1 patients and in none of the control group. The sensitivity of the presence of UBOs for the diagnosis of NF1 was 70% (CI 53–83%), with a false-negative rate of 30% (CI 27–47%), a specificity of 100% (CI 86–100%) and a false-positive rate of 0% (CI 0–14%). Conclusion Faced with the difficulties in diagnosing NF1 in children and the high frequency and specificity of the presence UBOs identified by MRI in our series, we recommend the inclusion of the presence UBOs as a diagnostic criterion for NF1 in children.     

Neuropsychological profile in Italian children with neurofibromatosis type 1 (NF1) and their relationships with neuroradiological data: Preliminary results

Background

Neurofibromatosis type 1 is a genetic disorder associated with cognitive deficits, learning disabilities and behavioral problems. These domains appear to have a still controversial debated association with local areas of T2-hyperintensities on MRI images, called unidentified bright objects (UBOs).

Neurological comorbidity in children with neurofibromatosis type 1

Background

The aim of this study was to determine the frequency of central nervous system comorbidities in children with neurofibromatosis type 1 (NF1).

Methods

We performed a nationwide survey to investigate neurological comorbidities in 3–15‐year‐old children with NF1 in Japan by sending questionnaires to pediatricians and pediatric neurologists. A secondary questionnaire was sent to the parents of identified NF1 patients to assess neurological comorbidities including headache, attention deficit–hyperactivity disorder (ADHD) Rating Scale (RS), and the Social Responsiveness Scale 2.

Results

The primary survey identified 760 NF1 patients, and the parents of 565 patients were sent the secondary questionnaire. The parental response rate was 25.7% (145; 63 girls, 81 boys, one unspecified). Among the patients, 42.9% (55/128; 35 girls, 20 boys) were reported to exhibit intellectual problems. On the ADHD‐RS, 40.2% (47/117) of NF1 patients aged 6–15 had ADHD (RS score >93rd percentile), with a rate of 47.7% in boys and 30.8% in girls. Furthermore, 20.2% of patients had suspected autism spectrum disorder (29/143; 10 girls, 19 boys), with Social Responsiveness Scale score ≥76. Headache was reported by 49.6% (61/123) of children over 5 years old, and 25.2% (31/123; 10 girls, 21 boys) reported migraine. Other neurological comorbidities included 20 cases of epilepsy (13.8%), 11 cases of optic nerve glioma (7.6%), five cases of brain tumor (3.4%), six cases of cerebrovascular disease (4.1%), and two cases of hydrocephalus (1.4%).

Conclusion

Intellectual problems, ADHD, autism spectrum disorder, and migraine are major neurological comorbidities in NF1.     

Neurofibromatosis in children with Rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma study IV

We identified all children enrolled in the Intergroup Rhabdomyosarcoma Study Group-IV with neurofibromatosis type I (NF1) and rhabdomyosarcoma. Among 1025 eligible patients, 5 (0.5 %) had NF1. Three children had relapses, two of whom died of progressive disease. Patients with NF1 and rhabdomyosarcoma should be treated with intensive contemporary therapy protocols.     

Pelvico-calyceal system rupture due to staghorn calculus with urinoma formation in a boy with neurofibromatosis type 1 and quadriplegia

Nephrolithiasis is a rare condition in children. The urinary tract rupture related to stones formation or migration is atypical in children, but creates serious consequences. We present a case of a 17-year-old quadriplegic patient with neurofibromatosis type 1 and urinoma due to the rupture of calyceal fornices in the course of nephrolithiasis. The boy was admitted with symptoms of severe pneumonia complicated with sepsis and prerenal acute kidney injury. Abdominal ultrasound revealed stone casts in both renal pelvises. Antibiotics, fluid therapy and diuretics were used to improve patient's condition. On the 28th day gross hematuria was observed. The patient's condition was stable, without signs of pain or discomfort. Abdomen ultrasound showed heteroechogenic structure (125 mm × 100 mm × 100 mm) localized between the lower surface of the liver and the right kidney. Contrast CT scan confirmed urinoma under the right kidney capsula. Because of the high risk of its rupture, decision of invasive evacuation of perirenal fluid was made. Using the percutaneous catheter 700 ml of bloody fluid was drained. After 10 days catheter was removed without recurrence of urinoma. Concluding, in children with prolonged immobilization this condition should be taken into consideration in differential diagnosis, also special attention should be paid for accompanying scarce symptoms.     

Complex epileptic (Foix–Chavany–Marie like) syndrome in a child with neurofibromatosis type 1 (NF1) and bilateral (opercular and paracentral) polymicrogyria

The association of brain malformations and symptomatic epilepsy in the setting of neurofibromatosis type 1 (NF1) is rarely reported. When it occurs, patients can present clinically with infantile spasms, focal seizures, generalized tonic clonic seizures or atypical absences. We report on a 10-year-old (molecularly proven) NF1 girl manifesting a complex epileptic syndrome resembling the Foix–Chavany–Marie spectrum (also known as opercular syndrome) associated with bilateral (opercular and paracentral lobular) polymicrogyria (PMG). Anecdotal cases of unilateral PMG in the setting of NF1 have been described in association with other-than-opercular epileptic syndromes. The typical clinical opercular syndrome consisting in mild mental retardation, epilepsy and pseudobulbar palsy is usually associated to bilateral perisylvian PMG (BPP)
Conclusion: To the best of our knowledge, the complex epileptic syndrome hereby reported has not been previously recorded in the setting of NF1. In addition, the present girl manifested all the clinical features of an opercular syndrome but had an asymmetrical PMG (not a BPP).     

Metastatic angiosarcoma arising in malignant peripheral nerve sheath tumor in a young patient with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of approximately one in 3,000 and a lifetime risk of malignancy estimated at 8–13%. Here, we report the case of a patient with NF1 who developed synchronous malignant peripheral nerve sheath tumors, one with a focus of angiosarcoma. He succumbed to metastatic angiosarcoma despite local resection and adjuvant chemotherapy. This case highlights the need for monitoring for malignancy in NF1 patients, the risks of sampling error during tumor biopsy, and the clinical decision ‐ making involved in choosing a therapeutic plan for a patient with multiple simultaneous malignancies.