Depression among adults with neurofibromatosis type 1: prevalence and impact on quality of life.

Neurofibromatosis type 1 (NF1) carries a significant psychosocial burden for affected individuals. The objective of this study was to measure the prevalence of depressive symptoms among a large sample of adults with NF1 and to quantify the impact of depressive symptoms on quality of life (QoL). This cross-sectional study used an Internet-based questionnaire to collect data from 498 adults who self-reported as having NF1. Using the Center for Epidemiologic Studies Depression (CESD) scale, 55% of all participants (61% of females and 43% of males) scored above 16, indicating a high likelihood of clinical depression. In a multivariate regression model controlling for demographics and potential confounders, depressive symptoms accounted for 32% of the variance in QoL as measured by the Quality of Life Index. This study is the largest to date and found the highest prevalence of depression compared to prior studies. Our data provide more compelling evidence that individuals with NF1 are at increased risk for psychiatric morbidity and suggest that this population should be routinely screened for depression. Because depression was found to be strongly associated with QoL and accounted for nearly one-third of the variance in QoL, it is likely that effectively treating depression may significantly enhance QoL for individuals with NF1.

Auditory dysfunction in Stickler syndrome.

OBJECTIVES: To characterize the natural history and possible mechanisms of hearing loss in Stickler syndrome (OMIM 108300; or hereditary progressive arthro-ophthalmopathy) and to determine if the auditory phenotype is a useful discriminating feature for the differential diagnosis of this group of disorders. DESIGN: Multifamily study. SETTING: Outpatient audiology and otolaryngology clinics at the Warren Grant Magnuson Clinical Center of the National Institutes of Health, Rockville, Md. SUBJECTS: Forty-six affected individuals from 29 different families segregating Stickler syndrome. INTERVENTIONS: Clinical audiologic and otolaryngological examinations were performed on all individuals, including pure-tone audiometry, speech audiometry, and middle ear immittance testing. Otoacoustic emissions, auditory brainstem response, infrared video electronystagmography, and temporal bone computed tomography were performed on a subset of participants. RESULTS: The hearing loss was most often sensorineural in adults, and approximately 28 (60%) of the 46 adult patients had 2 or more thresholds greater than the corresponding 95th percentile values for an age-matched, otologically normal population. The hearing loss most often affected high frequencies (4000-8000 Hz) and was generally no more progressive than that due to age-related hearing loss. Type A(D) tympanograms (classification using the Jerger model), indicating hypermobile middle ear systems, were observed in 21 (46%) of the 46 affected individuals. Computed tomography of the temporal bones revealed no inner ear malformations in 19 affected individuals. CONCLUSIONS: The hypermobile middle ear systems observed in ears with normal-appearing tympanic membranes represent a novel finding for Stickler syndrome and are likely to be a useful diagnostic feature for this disorder. The overall sensorineural hearing loss in type I Stickler syndrome is typically mild and not significantly progressive. It is less severe than that reported for types II and III Stickler syndrome linked to COL11A2 (OMIM 120290) and COL11A1 (OMIM 120280) mutations, respectively, or the closely related Marshall syndrome. This difference will be a useful discriminatory feature in the differential diagnosis of this group of disorders.

The hip in Stickler syndrome.

Stickler syndrome is an autosomal dominant connective tissue disorder with a prevalence similar to that of Marfan syndrome. No previous study has examined hip pain or abnormalities in a large series of patients with Stickler syndrome. The purpose of this study was to describe hip abnormalities and their correlation with age and chronic hip pain in a cohort of 51 patients followed at the National Institutes of Health. Ten percent of patients had protrusio acetabuli, 21% coxa valga, and 34% of adults had hip osteoarthritis. Sixty-three percent of all patients and 79% of adults had chronic hip pain. In addition, 16% of adult patients had a history of femoral head failure during youth. Arthritic changes and adult age were associated with hip pain. In summary, hip abnormalities are commonly observed in Stickler syndrome. Young patients require careful evaluation of hip pain, and regular screening of children with Stickler syndrome may be indicated for early detection of hip complications.

Comparative gene mapping in the species Muntiacus muntjac.

An extreme case of chromosomal evolution is presented by the two muntjac species Muntiacus muntjac (Indian muntjac, 2n = 6 [females], 7 [males]) and M. reevesi (Chinese muntjac, 2n = 46). Despite disparate karyotypes, these phenotypically similar species produce viable hybrid offspring, indicating a high degree of DNA-level conservation and genetic relatedness. As a first step toward development of a comparative gene map, several Indian muntjac homologs of known human type I anchor loci were mapped. Using flow-sorted, chromosome-specific Southern hybridization techniques, homologs of the protein kinase C beta polypeptide (PRKCB1) and the DNA repair genes ERCC2 and XRCC1 have been assigned to Indian muntjac chromosome 2. The male-specific ZFY gene was presumptively mapped to Indian muntjac chromosome Y2. Ultimate generation of a comparative physical map of both Indian and Chinese muntjac chromosomes will prove invaluable in the study of mammalian karyotype evolution.