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BACKGROUND AND AIMS: Endoscopic hand suturing (EHS) is a new technique for the closure of mucosal defects in the gastrointestinal tract. While this method was tested for wound closure after endoscopic submucosal dissection (ESD) in Japan, a feasibility test in a Western setting is lacking. In this study we present our first experience with EHS for different indications and in different anatomical locations. METHODS: Technical success of EHS as well as suturing speed were retrospectively determined for all available EHS cases in our center. Technical success was defined as complete closure of the mucosal defect or visually tight fixation of the target. RESULTS: 19 EHS procedures were performed in 17 patients (mean age 54.9 years, standard error of the mean [SEM] 4.2 years, male 53% [n=9]). Technical success was achieved in 78.9% (n=15). Total EHS operation time was 40.0 min (SEM 3.1 min) with 3.3 min (SEM 0.2 min) per single stitch. In a constant team of endoscopist and assistant mean stitch times declined significantly from the first four to the second four of eight cases (4.0 min [SEM 0.6] vs. 2.3 min [SEM 0.2], p=0.02). CONCLUSIONS: EHS was technically feasible and applicable in different anatomical locations. Further studies may elucidate a possible effect on complication rates of endoscopic resections.
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BACKGROUND AND AIMS: Patients with sigmoid-type achalasia can be challenging to treat with per-oral endoscopic myotomy (POEM). A short myotomy improves technical success, however outcomes have not previously been evaluated METHODS: This was a multicenter, international, retrospective study of patients who underwent POEM with short (≤ 4 cm) or standard esophageal myotomy. Outcomes included clinical and technical success, procedural adverse events, and reflux rates. RESULTS: A total of 109 patients with sigmoid achalasia (sigmoid = 74, advanced sigmoid = 35) underwent POEM across 13 centers (Short myotomy = 59, standard = 50). Technical success was 100% across both groups. Patients who underwent short myotomy had a significantly shorter mean procedure time (57.7 ± 27.8 vs 83.1 ± 44.7 minutes, p = 0.0005). A total of 6 AEs were recorded in 6 patients (5.5%; 4 mild, 2 moderate); AE rate was not significantly different between short and standard groups. Ninety-eight patients had follow-up data (median = 3.6 months [IQR, 1-14]) months). Clinical success was 94% (short = 93%; standard = 95%, p = 0.70) and did not differ based on achalasia subtype or sigmoid achalasia severity. Twenty-one (22%) patients reported post-POEM reflux and 44% (16/36) had objective evidence of pathologic reflux. Rates of pathologic reflux were significantly increased in the standard vs short group (OR 18.0 [95% CI: 2.0 - 159.0]; p = 0.009). CONCLUSIONS: POEM with short myotomy is effective and safe for the short-term treatment of sigmoid and advanced sigmoid achalasia. Short myotomy may lead to less reflux than standard myotomy.
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BACKGROUND: This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). METHODS: 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. RESULTS: AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. CONCLUSION: BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.
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Inteligência Artificial , Esôfago de Barrett , Neoplasias Esofágicas , Esofagoscopia , Gravação em Vídeo , Humanos , Esôfago de Barrett/diagnóstico , Neoplasias Esofágicas/diagnóstico , Esofagoscopia/métodos , Competência Clínica , Sensibilidade e Especificidade , Sistemas de Apoio a Decisões Clínicas , Biópsia , FemininoRESUMO
BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95â%). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.
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COVID-19 , Hemostase Endoscópica , Hemostáticos , Humanos , Gastroscópios , Estudos de Viabilidade , Pandemias , Resultado do Tratamento , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hemostase Endoscópica/métodosRESUMO
BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20-40mm) sessile or flat colorectal polyps. METHODS: In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. RESULTS: En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P = .611). CONCLUSIONS: UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.
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Pólipos Adenomatosos/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Pólipos Adenomatosos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pólipos do Colo/patologia , Colonoscopia/efeitos adversos , Neoplasias Colorretais/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Duração da Cirurgia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
BACKGROUND: COVID-19 is a viral disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), first described in 2019, with a significant impact on everyday life since then. In December 2020, the first vaccine against COVID-19 from BioNTech/Pfizer was approved for the first time. However, little is known about the immune response to vaccination in patients with inflammatory bowel disease (IBD) and immunomodulators or biologics. The aim of our study was to investigate antibody response to SARS-CoV-2 vaccination in patients with IBD receiving immunomodulators or biologics compared to healthy controls. METHODS: This was a single-center study with a retrospective observational design. Seventy-two patients with ulcerative colitis or Crohn's disease were included. Matching data from 72 healthy employees of our hospital were used as the control group. Data were matched by propensity score to patients with IBD. Blood samples were taken from both groups for antibody response, and both groups received an accompanying questionnaire. RESULTS: Sixty-five (90.3%) patients of the IBD group reported taking immunomodulatory therapy. The mean antibody level for all IBD patients was 1,257.1 U/mL (standard deviation [SD] 1,109.626) in males and 1,500.1 U/mL (SD 1142.760) in female IBD patients after full vaccination. Compared to the healthy group, reduced antibody response could be detected (IBD group 1,383.76 U/mL SD 1,125.617; control group 1,885.65 U/mL SD 727.572, p < 0.05). In this group, blood samples were taken with an average of 61.9 days after the first vaccination. There was no vaccination failure in the IBD group after 2 vaccinations. After the first vaccination, side effects, including muscle pain, pain at the injection site, and fatigue, were reported more often in IBD patients than in the control group (total symptoms IBD group 58.3%, control group 34.5%, p < 0.007). The opposite occurred after the second vaccination when side effects were higher in the control group (total symptoms IBD group 55.4%, control group 76%, p = 0.077). There was a trend to a reduced immune response in elderly patients. Disease duration and concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on the immune response. However, longer time to last medication given and time passed to vaccination in patients with IBD seems to have a positive impact on antibody levels. CONCLUSION: Overall, we could show a high antibody response to vaccination with COVID-19 in all patients with IBD after 2 vaccinations. Vaccination was well tolerated, and no other adverse events were detected. Concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on seroconversion. Further evaluation of antibody titers over time is mandatory to detect early the need for re-vaccination in these patients.
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COVID-19 , Doença de Crohn , Doenças Inflamatórias Intestinais , Idoso , Feminino , Humanos , Masculino , Formação de Anticorpos , Azatioprina/uso terapêutico , Estudos de Coortes , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Doença de Crohn/tratamento farmacológico , Fatores Imunológicos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Integrinas , Metotrexato/uso terapêutico , Estudos Retrospectivos , SARS-CoV-2 , Centros de Atenção Terciária , Fator de Necrose Tumoral alfaRESUMO
INTRODUCTION: The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy. METHODS: A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients. RESULTS: In total, only 3 of 185 IBD patients (1.6â%) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5â% developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0â% vs. 10.6â%, pâ<â0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2â%, active IBD 23.3â% pâ<â0.05). IBD-specific therapy remained unchanged in 115 patients (71.4â%); the most common change was an interruption of systemic therapy (16.2â%). DISCUSSION: New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.
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COVID-19 , Doenças Inflamatórias Intestinais , COVID-19/complicações , Teste para COVID-19 , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos RetrospectivosRESUMO
Background: The endoscopic assessment of colorectal malignancies primarily aims at deciding on the local resectability. Local resectability is defined by the risk of lymphonodal metastasis. Summary: The gross morphology as well as the surface and vessel patterns provide valuable information prior to endoscopic resection. Various classifications have been standardized to assist endoscopists during endoscopic assessment. Key Message: The macroscopic assessment of colorectal malignancies should include the Paris and laterally spreading tumor (LST) classification as well as chromoendoscopic assessments such as Kudo's pit pattern and the Japanese NBI Expert Team classifications to describe the vessel and surface patterns.
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BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a standard treatment option for achalasia patients. Treatment response varies due to factors such as achalasia type, degree of dilatation, pressure and distensibility indices. We present an innovative approach for treatment response prediction based on an automatic three-dimensional (3-D) reconstruction of the tubular oesophagus (TE) and the lower oesophageal sphincter (LES) in patients undergoing POEM for achalasia. METHODS: A software was developed, integrating data from high-resolution manometry, timed barium oesophagogram and endoscopic images to automatically generate 3-D reconstructions of the TE and LES. Novel normative indices for TE (volume×pressure) and LES (volume/pressure) were automatically integrated, facilitating pre-POEM and post-POEM comparisons. Treatment response was evaluated by changes in volumetric and pressure indices for the TE and the LES before as well as 3 and 12 months after POEM. In addition, these values were compared with normal value indices of non-achalasia patients. RESULTS: 50 treatment-naive achalasia patients were enrolled prospectively. The mean TE index decreased significantly (p<0.0001) and the mean LES index increased significantly 3 months post-POEM (p<0.0001). In the 12-month follow-up, no further significant change of value indices between 3 and 12 months post-POEM was seen. 3 months post-POEM mean LES index approached the mean LES of the healthy control group (p=0.077). CONCLUSION: 3-D reconstruction provides an interactive, dynamic visualisation of the oesophagus, serving as a comprehensive tool for evaluating treatment response. It may contribute to refining our approach to achalasia treatment and optimising treatment outcomes. TRIAL REGISTRATION NUMBER: 22-0149.
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Acalasia Esofágica , Esfíncter Esofágico Inferior , Imageamento Tridimensional , Manometria , Humanos , Acalasia Esofágica/cirurgia , Masculino , Feminino , Manometria/métodos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto , Esfíncter Esofágico Inferior/cirurgia , Esfíncter Esofágico Inferior/fisiopatologia , Estudos Prospectivos , Idoso , Esôfago/cirurgia , Esofagoscopia/métodos , Miotomia/métodos , Software , Cirurgia Endoscópica por Orifício Natural/métodos , Adulto JovemRESUMO
BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is often found in patients with gut dysbiosis such as irritable bowel syndrome. Recently, the association of SIBO and inflammatory bowel disease (IBD) has been described in some cases. While clinical symptoms might be similar in IBD and SIBO, treatment is quite different for both diseases. Therefore, the differentiation between SIBO or a flare in IBD patients is key to optimizing treatment for these patients. METHODS: We retrospectively investigated our patients with IBD receiving a glucose breath test for SIBO and correlated the results with the clinical symptoms (clinical remission or active disease). RESULTS: 128 patients with the diagnosis "colitis" were analyzed in our cohort. Fifty-three (41.4%) patients had Crohn's disease and 22 (17.2%) patients were suffering from ulcerative colitis. Seventy-four (57.8%) were female and 54 (42.2%) were male patients. A total of 18 (14.1%) patients had a positive testing for SIBO. Eleven (61.1%) cases were associated with CD patients and two (11.1%) with UC. IBD patients in clinical remission had a positive SIBO in six (19.4%) cases, while IBD patients with active disease were positive in nine (15.3%) cases. The proportion of positive SIBO in active IBD patients was higher; however, it did not reach significance. Older age was a risk factor for SIBO in patients with CD (p < 0.003). CONCLUSIONS: In our study, we could show that an increased amount of SIBO was found in IBD patients and was especially more frequent in patients with CD than in those with UC. In UC patients, SIBO rates were not different to patients with other gastrointestinal diseases investigated (e.g., infectious colitis, collagenous colitis, or irritable bowel syndrome). In active IBD, positive SIBO was detected more often numerically compared to quiescent disease; however, due to the low number of patients included, it was not significant. However, older age was a significant risk factor for SIBO in patients with CD. SIBO is of clinical relevance in the vulnerable patient cohort with IBD, and its real prevalence and impact needs to be investigated in further and larger clinical trials.
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BACKGROUND: Vedolizumab (VDZ) is a well-established and important therapeutic option in the treatment of patients with inflammatory bowel disease (IBD). However, the significance of therapeutic drug monitoring (TDM) with VDZ remains a contradictory field in daily clinical practice. Our study aims to clarify the predictive impact of VDZ drug levels in long-term clinical outcomes in a real-world cohort. METHODS: Patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from a tertiary IBD referral center at the University Hospital Augsburg, Germany, were enrolled in this single-center retrospective data analysis. Clinical and endoscopic data were collected at month 6, month 12, and at the last time of follow-up, and outcomes were correlated with VDZ levels at week 6. RESULTS: This study included 95 patients, 68.4% (n = 65) with UC, 24.2% (n = 23) with CD, and 7.4% (n = 7) with indeterminate colitis (CI). Patients with a mean VDZ treatment time of 17.83 months ± 14.56 showed clinical response in 29.5% (n = 28) and clinical remission in 45.3% (n = 43) at the end of the study. Endoscopic response occurred in 20.0% (n = 19) and endoscopic remission in 29.5% (n = 28) at the end of the study. The sustained beneficial effect of VDZ was also reflected in a significant change in biomarker levels. VDZ trough level at week 6 was determined in 48.4% (n = 46) with a mean of 41.79 µg/mL ± 24.58. A significant association between VDZ level at week 6 and both short and long-term outcomes could not be demonstrated. However, numerically higher VDZ levels were seen in patients with endoscopic and clinical improvement at month 6 and at the time of last follow-up. CONCLUSIONS: This study demonstrated efficacy and safety for VDZ in a real-world cohort. Although, for some parameters, a clear trend for higher VDZ levels at week 6 was seen, the efficacy of VDZ was not significantly correlated to VDZ level at week 6, which questions the predictive value of VDZ levels in the real world.
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BACKGROUND: Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype. For the first time we report about a patient with a 17q12 microdeletion who is affected by MRKH in combination with a vascular and soft tissue disorder. Repeatedly she suffered from kidney transplant failure caused by consuming membranous nephropathy. CASE PRESENTATION: A 38-year-old female patient had been diagnosed with right kidney aplasia, left kidney dysplasia and significantly impaired renal function during infancy. Aged 16 she had to start hemodialysis. Three years later she received her first kidney transplant. Only then she was diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic syndrome caused by de novo membranous nephropathy, as was a second kidney transplant years later. In addition, a hyperelasticity syndrome affects the patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, knees and hips. Her clinical picture resembles a combination of traits of a hypermobile and a vascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead, array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renal developmental genes HNF1ß and LHX1. CONCLUSIONS: Deletions of HNF1ß have recently drawn significant attention in pediatric nephrology as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast, membranous nephropathy represents an often-unaccounted cause of nephrotic syndrome in the adult population. A causative connection between theses two conditions has never been postulated, but is suggestive enough in this case to hypothesize it.
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Anormalidades Múltiplas/genética , Glomerulonefrite Membranosa/genética , Fenótipo , Transtornos 46, XX do Desenvolvimento Sexual , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/terapia , Adulto , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Anormalidades Congênitas , Feminino , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/terapia , Humanos , Rim/anormalidades , Ductos Paramesonéfricos/anormalidades , Recidiva , Síndrome de Smith-Magenis , Somitos/anormalidades , Coluna Vertebral/anormalidades , Útero/anormalidades , Vagina/anormalidadesRESUMO
The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level.
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Esofagite Eosinofílica , Inteligência Artificial , Esofagite Eosinofílica/diagnóstico , Esofagoscopia/métodos , Humanos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. METHODS: 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. RESULTS: By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. CONCLUSIONS: We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.