Anne Lovell

Social, emotional, and behavioral functioning of children with NF1

Children with neurofibromatosis type 1 (NF1) can have varying degrees of cognitive impairment, and are at risk for social, emotional, and behavioral dysfunction. We undertook an evaluation of social, emotional, and behavioral functioning of youth with NF1 and peers from multiple perspectives. We hypothesized that children with NF1 would have more psychosocial difficulties, which would be positively associated with neurological involvement. We compared 58 children with NF1, ages 7–15, with comparison classroom peers, classmates who were same race/gender and closest date of birth. Peer relationships, emotional well‐being, and behavior were evaluated from multiple perspectives in multiple settings. Results showed that teachers perceived children with NF1 as more prosocial (i.e., polite, helpful to others). Teachers and peers viewed children with NF1 as displaying less leadership behavior and as more socially sensitive‐isolated (i.e., often left out, trouble making friends). Children with NF1 had fewer friendships and were less well liked by peers. Mothers and fathers reported more problems with social functioning among children with NF1. Few group differences in emotional well‐being and behavior were identified according to child and father report. However, mothers perceived children with NF1 to have more emotional problems relative to comparison peers, predominantly among older children. Neurological involvement was significantly related to psychosocial problems. We conclude that children with NF1 are frequently socially isolated and rejected by peers; and that greater neurological involvement is associated with more emotional problems. Central nervous system involvement appears to play a key role in identifying children at risk for problems with friendships, social acceptance, and emotional functioning (i.e., depression).

Pediatric Plexiform Neurofibromas: Impact on Morbidity and Mortality in Neurofibromatosis Type 1

OBJECTIVE To characterize morbidity, mortality, and surgical outcomes in pediatric patients with symptomatic plexiform neurofibromas (PNFs). STUDY DESIGN 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 Childrens Hospital Medical Center between 1997 and 2007. RESULTS 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). CONCLUSIONS 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.

The Use of Magnetic Resonance Imaging Screening for Optic Pathway Gliomas in Children with Neurofibromatosis Type 1

OBJECTIVE To evaluate the utility of screening brain/orbital magnetic resonance imaging (MRI) in a large population of children with neurofibromatosis type 1 (NF1) over a 20-year period. STUDY DESIGN A retrospective analysis of clinical and imaging data from children with NF1 seen at a single center between 1990 and 2010 was performed. RESULTS During the 20-year study period, 826 individuals with NF1 (402 females, 424 males) ages 1-9 years were screened for optic pathway gliomas (OPGs) using brain/orbital MRI; 18% were identified with OPGs with a median age at detection of 3 years. Fifteen percent of patients with OPGs had radiologic or clinical progression requiring therapy. Children with chiasmatic and postchiasmatic tumors were more likely to require therapy compared with patients with prechiasmatic OPGs (P < .0001). Patients with visual deficits at the time of diagnosis were more likely to experience visual decline despite therapy when compared with patients treated based on radiologic progression (P < .012). CONCLUSIONS Our findings confirm that chiasmatic and postchiasmatic OPG in children with NF1 have the highest risk for progression and vision loss. Early identification of OPG by screening MRI prior to the development of vision loss may lead to improved visual outcomes. Children with negative brain and orbital MRI screening at age 15 months or later did not develop symptomatic OPGs.

Outcomes of a Genetics Education Program for Nursing Faculty

&NA; A multifaceted educational program designed to teach nursing faculty about genetics was first offered in 1997 and subsequently repeated on an annual basis. The specific aims of the program were to: 1) increase nursing faculty knowledge about genetics and its clinical application, and 2) increase genetics content taught in entry‐level nursing education programs. The major components of the program included an annual Genetics Summer Institute (GSI), pre‐planned follow‐up strategies, and continuing education offerings. Measured outcomes included significant improvement in nursing faculty genetics knowledge and increased amounts of genetics content in their curricula. The majority of surveyed faculty focused curriculum change efforts on lectures or courses for which they were personally responsible. Thirty‐one percent were working on, or had developed, elective nursing genetics courses after attending a GSI. These findings indicate that this program provided the necessary foundational instruction and resources to enable nursing faculty participants to bring about change in their curricula.

Genetic service providers' practices and attitudes regarding adolescent genetic testing for carrier status

Purpose: To characterize current practices and attitudes regarding testing adolescents for carrier status.Methods: Electronic survey of 294 genetic service providers from various professional organizations. Testing for predisposition and presymptomatic conditions was excluded from this study.Results: Eighty-three percent of providers had received requests to test adolescents for carrier status. Of these, 84% have performed testing. Providers cited adolescent desire, sexual activity/pregnancy, and adolescent competence as the main reasons for testing. Some providers who performed testing found the current guidelines unhelpful.Conclusion: Testing adolescents for carrier status is common for at least some conditions. The guidelines regarding genetic testing of adolescents may need to be updated to reflect current concerns and practices.

Lethal presentation of neurofibromatosis and Noonan syndrome.

Neurofibromatosis type 1 and Noonan syndrome are both common genetic disorders with autosomal dominant inheritance. Similarities between neurofibromatosis type 1 and Noonan syndrome have been noted for over 20 years and patients who share symptoms of both conditions are often given the diagnosis of neurofibromatosis–Noonan syndrome (NFNS). The molecular basis of these combined phenotypes was poorly understood and controversially discussed over several decades until the discovery that the syndromes are related through disturbances of the Ras pathway. We present an infant male with coarse facial features, severe supravalvar pulmonic stenosis, automated atrial tachycardia, hypertrophic cardiomyopathy, airway compression, severe neurological involvement, and multiple complications that lead to death during early infancy. The severity of clinical presentation and significant dysmorphic features suggested the possibility of a double genetic disorder in the Ras pathway instead of NFNS. Molecular analysis showed a missense mutation in exon 25 of the NF1 gene (4288A>G, p.N1430D) and a pathogenic mutation on exon 8 (922A>G, p.N308D) of the PTPN11 gene. Cardiovascular disease has been well described in patients with Noonan syndrome with PTPN11 mutations but the role of haploinsufficiency for neurofibromin in the heart development and function is not yet well understood. Our case suggests that a double genetic defect resulting in the hypersignaling of the Ras pathway may lead to complex cardiovascular abnormalities, cardiomyopathy, refractory arrhythmia, severe neurological phenotype, and early death.

Variability in laboratory reporting practices for regions of homozygosity indicating parental relatedness as identified by SNP microarray testing.

Purpose:Single-nucleotide polymorphism (SNP) microarrays are capable of detecting regions of homozygosity (ROH) that can suggest parental consanguinity or incest. This study was designed to describe the variable reporting practices of clinical laboratories in the United States regarding ROH found on SNP microarray tests, to discuss the follow-up practices of laboratory personnel when findings of ROH indicate consanguinity or incest, and to highlight the legal and ethical dilemmas faced by workers who have discovered these incidental findings.Methods:A 20-question survey was administered to microarray experts at 18 laboratories offering clinical SNP microarray tests. The results are presented using descriptive statistics.Results:There was variability in laboratory SNP microarray reporting practices with respect to information and interpretation of ROH findings. All the laboratories agreed that they have a duty to inform the ordering physician about results suggesting consanguinity or incest, but the follow-through practices varied among laboratories.Conclusions:This study discovered variability in reporting practices and follow-up procedures for microarray results that suggest parental consanguinity or incest. Our findings highlight the need for laboratory guidelines to standardize reporting practices for SNP microarray and other tests that are capable of detecting ROH.Genet Med 2012:14(12):971–976

Parental Distress, Family Functioning, and Social Support in Families With and Without a Child With Neurofibromatosis

OBJECTIVE To compare parental adjustment, social support, and family functioning between families of children with neurofibromatosis 1 (NF1) and a group of demographically similar comparison families, and to examine the impact of disease severity. METHODS Questionnaires were completed at home by parents of 54 children with NF1 (54 mothers and 42 fathers) and 51 comparison children (49 mothers and 32 fathers). RESULTS Few differences between groups were identified for parental distress, social support, or family environment. Greater neurological impairment in children with NF1 was associated with greater distress, more family conflict, less positive mealtime interactions, and less social support from the perspectives of mothers. CONCLUSIONS Overall, parents of children with NF1 appear similar to parents of comparison children. Mothers who have children with NF1 characterized by greater neurological impairment may be at risk for more difficulties. Future work exploring long-term adjustment for these mothers as well as interventions to ameliorate any potential difficulties may be appropriate.