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To characterize morbidity, mortality, and surgical outcomes in pediatric patients with symptomatic plexiform neurofibromas (PNFs).We conducted retrospective analysis of data from clinical records of surgical history and other neurofibromatosis type 1 (NF1)-related complications in children with PNFs seen at Cincinnati Children's Hospital Medical Center between 1997 and 2007.A total of 154 children with NF1 and PNFs were identified. Children with symptomatic PNFs had increased incidence of other NF1-related tumors (P.05). Patients with NF1 and PNFs had a higher mortality rate (5/154, 3.2%) when compared with patients without or with asymptomatic PNFs (2/366, 0.5%; P = .024). The most common morbidities leading to surgeries were neurologic, disfigurement, orthopedic, and airway complaints. Less extensive resection predicted a shorter interval to second surgery (P.0019). The highest recurrence was seen in tumors located in the head, neck, and thorax (P.001).These findings quantify the increased risk for additional tumors and mortality associated with symptomatic PNFs. Surgical interventions were required in many cases and resulted in added morbidity in some cases. Patients with PNFs were more likely to benefit from surgery when the indications were airway compression or disfigurement.

Lower leg bowing with tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1). The objective of the study is to determine if the geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1) differs from controls, and to characterize the osseous components of the tibia in NF1.Peripheral quantitative computed tomography (pQCT) of the lower limb was performed (90 individuals with NF1 without tibial and/or fibular dysplasia: 474 healthy individuals without NF1). Subjects were 4-18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and gender).Using pQCT, NF1 individuals without bowing of the lower leg have smaller periosteal circumferences (p0.0001), smaller cortical area (p0.0001), and decreased tibial cortical and trabecular bone mineral content (BMC) (p0.0001) compared to controls.Individuals with NF1 have a different geometry of the lower leg compared to healthy controls suggesting that NF1 haploinsufficiency impacts bone homeostasis although not resulting in overt anterolateral bowing of the lower leg.

Neurofibromatosis type 1 is diagnosed clinically based on the presence of two of seven criteria developed by a panel of experts in 1987. The sixth criterion focuses on skeletal findings and is as follows: "A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis." The wording for this criterion is misleading. In particular, "thinning of long bone cortex" is not the characteristic radiographic presentation, and no mention of long bone bowing is included. The distinctive clinical feature of long bone dysplasia in neurofibromatosis type 1 is anterolateral bowing of the lower leg (portion of the body delimited by the knee and ankle). The usual radiographic findings of long bone dysplasia in neurofibromatosis type 1 at first presentation, prior to fracture, are anterolateral bowing with medullary canal narrowing and cortical thickening at the apex of the bowing. We suggest that anterolateral bowing of the lower leg, with or without fracture or pseudarthrosis, is a more appropriate description of the primary finding that a clinician will use to fulfill the sixth diagnostic criterion for neurofibromatosis type 1. Clarification of this diagnostic criterion is important for the clinician and for research protocols. Appropriate interpretation will improve understanding of the natural history and pathophysiology of neurofibromatosis type 1.

Application of gene expression profiling to human diseases will be limited by availability of tissue samples. It was postulated that germline genetic defects affect blood cells to produce unique expression patterns. This hypothesis was addressed by using a test neurological disease-neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease caused by mutations of the NF1 gene at chromosome 17q11.2. Oligonucleotide arrays were used to survey the blood gene expression pattern of 12 NF1 patients compared to 96 controls. A group of genes related to tissue remodeling, bone development and tumor suppression were down-regulated in NF1 blood samples. In addition, there were blood genomic patterns for gender and age: Y chromosome genes showing higher expression in males, indicating a gene-dosage effect; and genes related to lymphocyte functions showing higher expression in children. The results suggest that genetic mutations can be manifested at the transcriptional level in peripheral blood cells and blood gene expression profiling may be useful for studying phenotypic differences of human genetic diseases and possibly providing diagnostic and prognostic markers.

Objective: To describe social and emotional problems in children and adolescents with neurofibromatosis type 1 (NF1) and propose interventions. Our hypothesis is that children with NF1 will have significantly more social and emotional problems, compared with their unaffected siblings and children in the general population. Study design: Forty-three children with NF1 and 22 unaffected siblings (ages 5 to 18 years) were assessed with a standardized test completed by parents and teachers (the Child Behavior Checklist). Results: As with other aspects of NF1, there was variable expressivity. However, when rated by parents, children with NF1 had significantly more problems in comparison with test norms or unaffected siblings on 7 of 8 scales: Social Problems, Attention Problems, Anxiety/Depression, Withdrawal, Thought Problems, Somatic Complaints, and Aggressive Behavior. Children with NF1 also scored lower than unaffected siblings on measures assessing sports and other activities. Teachers reported fewer differences. Conclusions: We propose interventions in the form of information for parents; early screening and treatment for speech, motor, and cognitive problems; and an increased level of intervention to prevent and treat psychologic problems, including systematic screening with standardized tests. (J Pediatr 1999;134:767-72)

Ten of 12 patients diagnosed with deletion 22q11.2 in infancy required a total of 26 hospitalizations during their first year of life. After heart disease, feeding and respiratory problems were the most frequent reasons for intervention.