Autistic Traits and Somatic Symptom Disorders: What Is the Link?

Alterations in sensory processing, a key component of autism spectrum disorder (ASD), have recently attracted increasing attention as they result in peculiar responses to sensory stimuli, possibly representing a risk factor for the development of somatic symptom disorder (SSD). Contextually, other features also associated with ASD, such as alexithymia, camouflaging and altered verbal, and non-verbal communication, have been suggested to represent risk factors for the occurrence and worsening of somatic symptomatology. The aim of this work was to review the available literature about the association between SSD and the autism spectrum. The results highlighted not only a higher prevalence of autistic features in patients suffering from SSD and a higher prevalence of reported somatic symptomatology in subjects with ASD but also how ASD subjects with co-occurrent somatic symptoms exhibit more severe autism-linked symptomatology. From the paper reviewed also emerged many shared features between the two conditions, such as alexithymia, altered sensitivity to sensory stimuli, cognitive inflexibility, intolerance of uncertainty, and an increased risk of experiencing stressful life events, which may provide an explanation for the correlation reported. Even though studies on the topic are still scant, the evidence reported suggests the importance of further assessing the correlation between the two disorders.

The association between sport type and eating/body image concerns in high school students: a cross-sectional observational study.

PURPOSE: Disordered eating and body image concerns are increasingly common among adolescents, possibly representing the underpinning of eating disorders (EDs). This cross-sectional observational study aimed at investigating the relationship between various patterns of sports involvement or inactivity, and the abovementioned psychopathological dimensions. METHODS: All adolescents attending their 3rd-5th Italian grade in a single high school reported their sociodemographic and anthropometric data, their weekly sports involvement, and filled the Eating Disorders Examination Questionnaire 6.0 (EDE-Q), the Body Uneasiness Test, and the Muscle Dysmorphia Disorder Inventory (for boys). Comparisons were performed considering sex, weekly hours of activity, and different sports type (none, individual, or team sports). RESULTS: Of 744 enrolled students, 522 (70.2%) completed the survey. Girls showed higher underweight rates, preference for inactivity or individual sports, and higher psychometric scores compared to boys. Among girls, no differences were found based on time spent exercising or sports type. Inactive boys displayed worse weight- and shape-based psychopathology, higher body uneasiness, and higher appearance intolerance compared to those who devoted more time to exercise. Among boys, individual and team sports were associated with lower EDE-Q scores compared to inactivity, whereas body uneasiness and appearance intolerance were lower only in team sports. CONCLUSIONS: The study confirms the presence of remarkable sex differences in eating and body concerns of adolescents. Among boys, sports involvement is tied to lower ED psychopathology, and preference for team sports may be associated with reduced concerns. Wider longitudinal studies on will clarify the direction and specificity of these findings. LEVEL OF EVIDENCE: Level V-Cross-sectional observational study.

Digital Twin for Civil Engineering Systems: An Exploratory Review for Distributed Sensing Updating.

We live in an environment of ever-growing demand for transport networks, which also have ageing infrastructure. However, it is not feasible to replace all the infrastructural assets that have surpassed their service lives. The commonly established alternative is increasing their durability by means of Structural Health Monitoring (SHM)-based maintenance and serviceability. Amongst the multitude of approaches to SHM, the Digital Twin model is gaining increasing attention. This model is a digital reconstruction (the Digital Twin) of a real-life asset (the Physical Twin) that, in contrast to other digital models, is frequently and automatically updated using data sampled by a sensor network deployed on the latter. This tool can provide infrastructure managers with functionalities to monitor and optimize their asset stock and to make informed and data-based decisions, in the context of day-to-day operative conditions and after extreme events. These data not only include sensor data, but also include regularly revalidated structural reliability indices formulated on the grounds of the frequently updated Digital Twin model. The technology can be even pushed as far as performing structural behavioral predictions and automatically compensating for them. The present exploratory review covers the key Digital Twin aspects-its usefulness, modus operandi, application, etc.-and proves the suitability of Distributed Sensing as its network sensor component.

Primary epithelioid angiosarcoma of the thyroid: A case report.

Angiosarcoma of the thyroid is a rare and aggressive primary malignant tumour of the thyroid. We report the case of a 69-year-old woman who presented with a red and sore skin area at the right-anterior region of the neck. Ultrasound examination and computed tomography scan showed a non-homogeneous mass in the right thyroid lobe. Fine needle aspiration cytology was suggestive of atypical vascular proliferation and so the patient underwent right thyroid lobectomy. The specimen measured 6 × 5 × 2.5 cm, and a reddish nodule was found, including a whitish central area of maximum 4 cm in diameter. Immunohistochemistry showed CD31 and ERG positivity, while thyroglobulin, calcitonin and TTF-1 expression were negative, indicating a diagnosis of angiosarcoma.

Quality of Life Before and After Transplantation in Solid Organ Recipients Referred to the North Italy Transplant program (NITp): A Cross-sectional Study.

INTRODUCTION: The interest in health-related quality of life (HR-QoL) has increased in the past few years. AIM: The aim of this study was to evaluate the HR-QoL before and after transplantation in solid organ recipients referred to the North Italy Transplant program. MATERIAL AND METHODS: This cross-sectional study was performed between 2010 and 2011. All consecutive recipients on the waiting list for liver, heart, or kidney transplantation were included and compared to all consecutive transplanted patients at 6 and 24 months of follow-up after transplantation. The HR-QoL was evaluated with the 36-item Short Form Health Survey (SF-36) and the Profile of Mood States (POMS). Questionnaires were self-reported anonymously. Descriptive statistical analyses were performed. RESULTS: Four hundred eleven patients were interviewed: 146 patients (35.5%) were on the waiting list, 137 (33.3%) were transplanted 6 months before the interview, and 128 (31.1%) were transplanted 24 months before the interview. Patients on the waiting list had a lower SF-36 score for all items than did transplanted patients after both 6 and 24 months. According to POMS results, patients on the waiting list had a higher prevalence of depression, tension, anger, fatigue, and confusion than did transplanted patients. CONCLUSIONS: Patients on the waiting list showed a worse quality of life compared to patients after transplantation as demonstrated by SF-36 and POMS results. These findings should be confirmed in a cohort study.

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature.

BACKGROUND: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. AIM: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. METHODS: A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. RESULTS: A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). CONCLUSIONS: The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

Fatal varicella in immigrants from tropical countries: Case reports and forensic perspectives.

The primary Varicella Zoster Virus (VZV) infection results in varicella, a generally benign, self-limiting disease in immunocompetent children. Despite the usual course a possible fatal evolution of the primary infection is observed predominantly in immunocompromised subjects and in adults, especially emigrating from tropical regions. Two cases of fatal varicella have been investigated and discussed. Death occurred in two patients over 40 years of age, coming from South Asia and receiving chronic immunosuppressive therapy. The forensic expert must be cautious and consider all clinical records in managing fatal varicella cases, bearing in mind risk factors and pre-existing conditions such as age, geographical provenance and pathological comorbidity, which may lead to a bad prognosis irrespective of therapies. Based on the severe and fatal course observed in the reported cases, an extension of the immunization program appears advisable for immigrants from tropical countries, especially before scheduled immunotherapy.

Sleep-related violence and sexual behavior in sleep: a systematic review of medical-legal case reports.

OBJECTIVE: To review systematically medical-legal cases of sleep-related violence (SRV) and sexual behavior in sleep (SBS). SEARCH METHODS: We searched Pubmed and PsychINFO (from 1980 to 2012) with pre-specified terms. We also searched reference lists of relevant articles. SELECTION CRITERIA: Case reports in which a sleep disorder was purported as the defense during a criminal trial and in which information about the forensic evaluation of the defendant was provided. DATA EXTRACTION AND ANALYSIS: Information about legal issues, defendant and victim characteristics, circumstantial factors, and forensic evaluation was extracted from each case. A qualitative-comparative assessment of cases was performed. RESULTS: Eighteen cases (9 SRV and 9 SBS) were included. The charge was murder or attempted murder in all SRV cases, while in SBS cases the charge ranged from sexual touching to rape. The defense was based on sleepwalking in 11 of 18 cases. The trial outcome was in favor of the defendant in 14 of 18 cases. Defendants were relatively young males in all cases. Victims were usually adult relatives of the defendants in SRV cases and unrelated young girls or adolescents in SBS cases. In most cases the criminal events occurred 1-2 hours after the defendant's sleep onset, and both proximity and other potential triggering factors were reported. The forensic evaluations widely differed from case to case. CONCLUSION: SRV and SBS medical-legal cases did not show apparent differences, except for the severity of the charges and the victim characteristics. An international multidisciplinary consensus for the forensic evaluation of SRV and SBS should be developed as an urgent priority.

Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1.

OBJECTIVE: We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. METHODS: Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. RESULTS: History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. CONCLUSIONS: The two asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS.

DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.

STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

Plasmapheresis-resistant acute humoral rejection successfully treated with anti-C5 antibody.

Even if kidney graft survival has improved during the last decades, sensitized pediatric patients are an emerging problem. We describe a 17-yr-old male who lost his first graft due to chronic rejection becoming hyperimmunized (CDC PRA 99.61%). A desensitization protocol based on high-dose IVIG, PP, and two Mabthera(®) infusions was performed with minor response (CDC PRA post-desensitization 80%). One month after his second non-living transplant, he developed a biopsy-proven AMR; post-transplant immunological monitoring showed the presence of donor-specific anti-DQ5 antibodies (DSA, MFI 20.000). He received methylprednisolone pulses and 45 PP sessions without clinical response; eculizumab was then used to salvage a kidney undergoing severe PP-resistant rejection. A biopsy performed after the fourth eculizumab infusion showed complete resolution of AMR. Eculizumab infusions were then continued for the first year post-transplantation. Two yr after transplantation, graft function is stable. Anti-C5 therapy may represent an effective therapeutic option in pediatric patients with PP-resistant AMR.

In kidney transplant patients, alemtuzumab but not basiliximab/low-dose rabbit anti-thymocyte globulin induces B cell depletion and regeneration, which associates with a high incidence of de novo donor-specific anti-HLA antibody development.

In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared. Transitional B cells transiently increased 2 mo posttransplant. At month 6 posttransplant, pregerminal center B cells emerged, a process promoted by increased BAFF serum levels. Thereafter, B cell counts increased progressively, mainly due to expansion of naive B cells. Conversely, Bas/rATG did not modify the B cell phenotype throughout the follow-up period. Alemtuzumab was associated with a higher incidence of de novo DSA compared with Bas/rATG. DSA development was predicted by changes in the B cell compartment and correlated with worse long-term graft function. Thus, alemtuzumab-induced B cell depletion/reconstitution may promote chronic humoral responses against the graft.

Narcolepsy with cataplexy mimicry: the strange case of two sisters.

We report on two sisters, 17 and 12 years of age, with clinical features suggesting narcolepsy with cataplexy (NC): daytime sleepiness, spontaneous and emotionally triggered sudden falls to the ground, and overweight/obesity. MSLT showed borderline sleep latency, with 1 and 0 sleep onset REM periods. HLA typing disclosed the DQB1*0602 allele. Video-polygraphy of the spells ruled out NC diagnosis by demonstrating their easy elicitation by suggestion, with wake EEG, electromyographic persistence of muscle tone, and stable presence of tendon reflexes (i.e., pseudo-cataplexy), together with normal cerebrospinal hypocretin-1 levels. Our cases emphasize the need of a clear depiction of cataplexy pattern at the different ages, the usefulness of examining ictal neurophysiology, and collecting all available disease markers in ambiguous cases.

Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.

IMPORTANCE: Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE: To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS: Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES: Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level. RESULTS: Short REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%). CONCLUSIONS AND RELEVANCE: Among patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

Intravascular macrophages in cardiac allograft biopsies for diagnosis of early and late antibody-mediated rejection.

BACKGROUND: The aim of our study was to evaluate the role of intravascular macrophages in the diagnosis of early and late antibody-mediated rejection (AMR) on endomyocardial biopsies (EMBs). METHODS: We reviewed 1,420 consecutive EMBs from 131 patients and selected 75 C4d+ EMBs. The C4d+ group was compared with a control group (66 patients) matched for age, gender, date of transplantation, follow-up, immunosuppressive regimen and primary heart disease. A total of 141 EMBs were evaluated. Immunoperoxidase staining for C4d and CD68 were performed. Post-transplant IgG anti-HLA reactivity was investigated by Luminex technology. Clinical data were also collected. Fourteen EMBs were available from 11 symptomatic AMR patients. RESULTS: Of the 141 EMBs evaluated, 53 were positive for intravascular macrophages (CD68); among them, 32 were also positive for C4d (32 of 53, 60.4%). Of the 88 CD68- EMBs, 43 were also C4d+ (43 of 88, 48.9%). Of the 53 CD68+ EMBs, 30 EMBs were within the first year since transplantation (30 of 53, 57.8%), and among these 21 were also positive for C4d (21 of 30, 70.0%). In the late period, among the 23 CD68+ EMBs (23 of 53, 42.2%) 11 were also positive for C4d (11 of 23, 47.8%). In the early period, intravascular macrophages were more common in symptomatic (3 of 3, 100%) than asymptomatic (3 of 11, 27.3%) patients. Sensitivity and specificity of intravascular macrophages in predicting donor-specific antibodies (DSA) within the first year were 50.0% and 100.0%, respectively. CONCLUSIONS: Intravascular macrophages predict C4d, DSA and symptoms early after transplantation; however, in the late period, they are unable to identify patients with circulating DSA, C4d and/or symptoms.

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.