©American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE Emotional functioning of patients with neurofibromatosis tumor suppressor syndrome Daphne L. Wang, BS1, Kelly B. Smith, PhD2,3, Sonia Esparza, BA1, Fawn A. Leigh, MD1, Alona Muzikansky, MS4, Elyse R. Park, PhD, MPH2,5 and Scott R. Plotkin, MD, PhD1 Purpose: Although patients with neurofibromatosis are predisposed neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis, and to multiple nerve sheath tumors that can develop anywhere in the emotional functioning was not significantly associated with disease body and cause significant morbidity (e.g., hearing loss; pain), little severity. However, increased symptoms of depression and anxiety, research has examined emotional correlates of neurofibromatosis. higher levels of perceived stress, and lower levels of self-esteem were The purpose of this study was to examine emotional functioning associated with a higher frequency of self-reported medical visits in among adult patients with neurofibromatosis. the past year (P values ≤0.05). Methods: A total of 248 patients with neurofibromatosis (neu- Conclusion: Neurofibromatosis appears to be associated with rofibromatosis 1, neurofibromatosis 2, or schwannomatosis) who reduced emotional functioning. Although further research is needed, received care at a specialized clinic completed validated measures to these findings suggest a role for a multidisciplinary treatment assess symptoms of depression and anxiety, level of perceived stress, approach to address emotional distress among adult patients with and self-esteem. neurofibromatosis. Results: Patients with neurofibromatosis reported significantly more Genet Med 2012:14(12):977–982 symptoms of depression and anxiety, higher levels of perceived stress, and lower levels of self-esteem as compared with general population Key Words: emotional function; neurofibromatosis 1; neurofibro- norms. No significant differences were found among patients with matosis 2; schwannomatosis; tumor suppressor syndromes INTRODUCTION affect the nervous system, eyes, and skin.3,4 Currently, there are The neurofibromatoses (neurofibromatosis (NF)1, NF2, and only a handful of clinics in the United States that provide special- schwannomatosis; OMIM #162200, #101000 and 162091, ized care for adult patients with NF; the majority of such patients respectively) are the most common neurologic tumor suppres- will be cared for by primary-care physicians. Given the limited sor syndromes and are a group of related neurogenetic condi- number of specialized clinics, as well as the substantial morbidity tions characterized by a predisposition to develop multiple nerve associated with the neurofibromatoses, it is imperative for clini- sheath tumors. NF1 is the most common of these conditions cians to be familiar with these conditions. with a birth incidence of ~1:2,700.1 NF2 and schwannomatosis Anecdotal evidence is that patients with NF1, NF2, and are less common than NF1. The estimated birth incidence of schwannomatosis express concern about their present and NF2 is 1:33,0001; schwannomatosis may have an incidence rate future health status, and about the possibility of transmitting similar to that of NF2.2 These genetic conditions are transmit- NF to their offspring. Research with non-NF patient popula- ted in autosomal dominant fashion with 50% risk to offspring of tions also highlights the emotional distress that may accompany affected parents. Symptom severity varies widely among patients; chronic medical conditions.5 To date, however, research regard- however, the hallmark manifestation of NF1, NF2, and schwan- ing the potential psychological impact of NF in adulthood has nomatosis is nerve sheath tumors, including neurofibromas and been generally restricted to a few studies that have examined schwannomas. These histologically benign tumors can occur quality of life among patients with NF16–8 or NF29 and to a few anywhere in the body and often cause significant morbidity that have assessed psychiatric morbidity among patients with including disfiguring cutaneous tumors (NF1), complete hearing NF1 only.10–12 For example, 12-year follow-up of 48 Swedish loss, facial weakness, and poor gait (NF2), and chronic disabling patients with NF1 (37 were evaluated for psychiatric disorders pain (schwannomatosis). In addition to the increased risk of at follow-up) found that one-third of the patients met criteria benign tumors, patients with these genetic syndromes may have for at least one psychiatric disorder.11 Psychiatric disorders were or develop malignant tumors and nontumor manifestations that significantly more common among patients as compared with D.L.W. and K.B.S. contributed equally to this publication. E.R.P. and S.R.P. contributed equally to this publication. 1Department of Neurology and Cancer Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA; 2Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA; 3Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada; 4Biostatics Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA; 5Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Correspondence: Scott R. Plotkin ([email protected]) Submitted 30 March 2012; accepted 7 June 2012; advance online publication 9 August 2012. doi:10.1038/gim.2012.85 GENETICS in MEDICINE | Volume 14 | Number 12 | December 2012 977 ORIGINAL RESEARCH ARTICLE WANG et al | Emotional function of patients with NF controls. At least one study also examined responses to receiv- marital status. Health-care utilization was assessed by the num- ing a diagnosis among 20 patients with NF2 and found that eight ber of medical visits in the past 12 months. patients reported negative emotional responses such as anxiety.13 To our knowledge, however, in-depth studies of psychological Center for Epidemiologic Studies Depression Scale. The Center and emotional functioning are rare in the NF literature and no for Epidemiologic Studies Depression Scale (CES-D) contains such studies have included patients with schwannomatosis. 20 items that measure the frequency with which symptoms of To address this gap in the literature, we examined emotional depression were experienced during the past week.15 Items are functioning in adult patients with NF1, NF2, and schwannoma- rated using a scale from 0 (rarely or none of the time; <1 day) tosis (both in comparison with population norms and between to 3 (most or all of the time; 5–7 days); possible scores range patient groups). The term emotional functioning was used in this from 0 to 60 and higher scores indicate more symptoms. The study to refer to patients’ self-reported symptoms of depression, CES-D has been shown to discriminate between general and symptoms of anxiety, and levels of stress and self-esteem. We psychiatric patient samples, and although the CES-D is not a also examined whether clinical factors—specifically, skin mani- diagnostic tool, a score of 16 or greater is indicative of clini- festation (NF1), hearing impairment, walking status, and facial cally significant symptoms of depression. The general popula- function (NF2), and pain (schwannomatosis)—were associated tion scores reported by Radloff15 were utilized for comparison with patients’ levels of emotional functioning. Finally, given that purposes in our study. One item (i.e., I feel fearful) was imputed decreased emotional functioning is associated with increased for the first 200 patients using means replacement because of a use of health-care services among patients with chronic medical typographical error. conditions,14 we assessed whether level of emotional function- ing was associated with the number of self-reported medical Perceived Stress Scale-4. The Perceived Stress Scale-4 contains visits (a proxy of health-care utilization) within the past year. four items that assess the degree to which situations in one’s life Although we expected patients to report poorer levels of emo- during the past month are viewed as stressful.16 Items are rated tional functioning as compared with population norms, this using a scale from 0 (never) to 4 (very often). Possible scores study was mainly exploratory and descriptive in nature. range from 0 to 16, with higher scores indicating higher lev- els of perceived stress. In this study, general population norms MATERIALS AND METHODS based on a probability sample of US adults were used for com- This project was a cross-sectional study examining emotional parison purposes.17 functioning among adult patients with NF. Patients who were 18 years or older with a clinical diagnosis of NF1, NF2, or Rosenberg Self-Esteem Scale. The Rosenberg Self-Esteem Scale schwannomatosis and who were seen in The Family Center for consists of 10 items that assess global self-esteem (overall evalu- Neurofibromatosis at Massachusetts General Hospital between ation of one’s value or worth).18 Items are rated using a scale January and November 2010 were recruited. This clinic special- from 0 (strongly disagree) to 3 (strongly agree), and possible izes in the care of adult patients with NF and sees a large vol- scores range from 0 to 30. Higher scores on the Rosenberg ume of patients annually (435 adult patients in 2010). Patients Self-Esteem Scale indicate higher levels of self-esteem. General who were unable to comprehend