Variable Phenotypic Expression Research Articles

Quantitative characterization of proximate sensing canopy traits in the SoyNAM population

AbstractThe average increase of soybean [Glycine max (L.) Merr.] grain yield per year is not enough to meet the estimated need by 2050. Contributing factors may include narrowing genetic diversity in cultivated soybean germplasm arising from direct selection for grain yield and insufficient knowledge of the genetic influences on physiological traits associated with grain yield. Canopy development plays a critical role in the light intercepted by soybean crops throughout the growing season. Rapid canopy closure facilitates complete light interception and optimizes growth dynamics, ultimately increasing biomass accumulation and grain yield. This study sought to use ground‐based digital imagery as a phenotyping tool for quantitative characterization of seasonal canopy coverage and light interception in the genetically diverse Soybean Nested Association Mapping (SoyNAM) population. We took weekly measurements of canopy coverage from early vegetative to mid‐reproductive growth for 5,600 recombinant inbred lines during the 2013 and 2014 seasons. An asymptotic logistic growth curve fit to the coverage data allowed us to estimate daily changes in canopy coverage in the intervals between the sampling dates, enabling calculation of canopy dynamic parameters. These parameters included average canopy coverage, cumulative intercepted photosynthetically active radiation for the total sampling period, vegetative growth period, reproductive growth period, and the number of days required to reach 30, 50, and 70% canopy coverage. Variance component estimation showed that genetic differences among families significantly influenced variation in phenotypic expression for all canopy parameters. The narrow‐sense heritabilities for all canopy parameters were high (h2 = .81–.90), suggesting opportunities for genetic gains in canopy development through selection of superior genotypes.

Mutations in Ribosomal Protein S19 Gene and Diamond Blackfan Anemia: Wide Variations in Phenotypic Expression

AbstractMutations of the ribosomal protein S19 (RPS19) gene were recently identified in 10 patients with Diamond Blackfan anemia (DBA). To determine the prevalence of mutations in this gene in DBA and to begin to define the molecular basis for the observed variable clinical phenotype of this disorder, the genomic sequence of the 6 exons and the 5′ untranslated region of the RPS19 gene was directly assessed in DBA index cases from 172 new families. Mutations affecting the coding sequence of RPS19 or splice sites were found in 34 cases (19.7%), whereas mutations in noncoding regions were found in 8 patients (4.6%). Mutations included nonsense, missense, splice sites, and frameshift mutations. A hot spot for missense mutations was identified between codons 52 and 62 of the RPS19 gene in a new sequence consensus motif W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y. No correlation between the nature of mutations and the different patterns of clinical expression, including age at presentation, presence of malformations, and therapeutic outcome, could be documented. Moreover, RPS19 mutations were also found in some first-degree relatives presenting only with isolated high erythrocyte adenosine deaminase activity and/or macrocytosis. The lack of a consistent relationship between the nature of the mutations and the clinical phenotype implies that yet unidentified factors modulate the phenotypic expression of the primary genetic defect in families with RPS19 mutations.

Abstract 14042: Weight Loss Favorably Impacts Left Ventricular Mass and Wall Thickness by CMR and CT in Patients With Hypertrophic Cardiomyopathy: A Retrospective Case Series

Introduction: Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart disease with variable phenotypic expression. While pathogenic variants in sarcomeric genes are considered responsible for the development of left ventricular (LV) hypertrophy, environmental modulation of phenotype may explain the known heterogeneity. Obesity is common in HCM patients and is associated with increased LV mass in the general population. Hypothesis: We hypothesized that weight loss in obese patients with HCM would be associated with a decrease in LV mass and maximal wall thickness. Methods: Patients with HCM who achieved therapeutic weight loss and underwent cardiac MRI (CMR) or computed tomography (CT) before and afterwards were included. Standard LV measurements including wall thickness in an 18-segment model were performed blindly with respect to name, time and BMI for un-biased comparison. Results: We included 6 patients (2 female, age 55 ± 6.5 years, baseline BMI = 36.7 ± 5.2 kg/m 2 ) who achieved 16.3 ± 10.8 kg weight loss after 35 ± 12 months with diet and exercise (n=4) or bariatric surgery (n=2). After weight loss, we observed a mean proportional decrease in total LV mass of 25 ± 16% (p=0.004), and a 19 ± 7% decrease in indexed LV mass (p=0.007). Furthermore, there was a numerical decrease in mean wall thickness in 14 out of 18 LV segments measured; 9 segments had more than a 10% decrease. The most noticeable changes were at the basal inferolateral wall (25 ± 13% decrease) and basal inferoseptum (19 ± 18%) decrease (Table). Conclusions: In this series of patients with HCM, weight loss favorably affected LV mass and wall thickness. Further research is needed to explore the impact of weight loss on HCM phenotypic expression and symptoms.

Alagille Syndrome: Diagnostic Challenges and Advances in Management.

Alagille syndrome (ALGS) is a multisystem disease characterized by cholestasis and bile duct paucity on liver biopsy in addition to variable involvement of the heart, eyes, skeleton, face, kidneys, and vasculature. The identification of JAG1 and NOTCH2 as disease-causing genes has deepened our understanding of the molecular mechanisms underlying ALGS. However, the variable expressivity of the clinical phenotype and the lack of genotype-phenotype relationships creates significant diagnostic and therapeutic challenges. In this review, we provide a comprehensive overview of the clinical characteristics and management of ALGS, and the molecular basis of ALGS pathobiology. We further describe unique diagnostic considerations that pose challenges to clinicians and outline therapeutic concepts and treatment targets that may be available in the near future.

Further delineation of HIDEA syndrome

Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in P4HTM, which encodes an atypical member of the prolyl 4-hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole-exome sequencing (WES) revealed novel disease-causing variants in P4HTM. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment/developmental delay, and hypotonia, which seem to be consistent findings. One patient only presented with hypotonia, developmental delay, and abnormal eye movements, which highlights the challenge in diagnosing milder cases with this new syndrome. Other notable features include mild facial dysmorphism, obesity, and brain dysmyelination and atrophy. We conclude that HIDEA is a highly variable syndrome and suspect that a large fraction of patients will be diagnosed via reverse phenotyping after recessive P4HTM variants are identified by agnostic genomic sequencing assays.

Clinical characteristics and comorbidity associated with female gender in obsessive-compulsive disorder

IntroductionObsessive-compulsive disorder (OCD) is a heterogeneous condition characterized by largely variable phenotypic expressions. Previous findings suggested that gender may be a relevant factor in mediating this heterogeneity. The present study aimed at exploring gender differences in a large clinical sample of Italian OCD patients. MethodsSocio-demographic and clinical variables of a sample of 229 consecutive OCD outpatients were included in a common database. Patients were assessed through structured clinical interviews, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale. ResultsFemale OCD patients were more likely than males to have lifetime psychiatric comorbidities (72.6% vs 56.9%; p < 0.05), poly-comorbidities being twice as high compared to males. The female group also showed a significant later onset of symptoms (63.7% vs 44.8%; p < 0.005) and a higher age at first treatment (30.98 ± 13.1 years vs 27.81 ± 11.3; p < 0.005). Moreover, the female subgroup presented higher rates of cleaning and washing compulsions, compared to the male subgroup (28.7% vs 12.6% in the male group; p < 0.005). ConclusionsThe current study supports the notion that OCD in female gender is frequently a comorbid condition with other specific clinical characteristics compared to male patients. These findings should be considered in epidemiologic and therapeutic perspectives.

GORLIN-GOLTZ SYNDROME WITH RARE ASSOCIATED FINDS: A CASE REPORT OF 17-YEAR FOLLOW-UP

Gorlin-Goltz syndrome (GGS) is an inherited autosomal dominant disorder caused by mutations in the patched tumor suppressor gene, which has variable phenotypic expressivity. Gorlin and Goltz defined the syndrome by 3 main characteristics: multiple basal cell carcinomas, keratocystic odontogenic tumors, and skeletal abnormalities anomalies. Many neurologic, ophthalmic, endocrine, and genital manifestations are known to be associated with this syndrome. This study reports the case of a 27-year-old woman with GGS who was followed-up for 17 years. She was submitted to imaging tests and biopsies that could diagnose the presence of maxillary keratocystic odontogenic tumors and basal cell carcinomas, which were treated with decompression, marsupialization, and surgical removal; calcification of the cerebral sickle was also found. In addition to these common manifestations, this case revealed the presence of other less common comorbidities that are rarely described: arachnoid cysts, teratoma, fibrothecoma, eyelid cysts, and focal osteolysis on lower member bones, diagnosed with simple bone cyst.

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer.

Interstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives. The consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented. For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6-65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic. This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

A Case Report of Klebsiella sepsis in an Infant with Goldenhar Syndrome: Association or Coincidence

Goldenhar syndrome (GS) is a rare congenital disorder of the development of first and second branchial arches. The born neonate may exhibit orofacial, auricular, skeletal, and solid organ involvement with variable phenotypic expression. The pathogenesis and long-term implication of GS is still under study. Multidisciplinary management is the key in lifelong management of GS. There is a challenge identifying this syndrome in low-resource setting. We describe in this case report about a neonate with typical phenotypic features and late-onset Klebsiella sepsis.

Rare RYR2 p.Thr85Ile variant is associated with catecholaminergic polymorphic ventricular tachycardia

Mutations in the cardiac ryanodine receptor 2 gene (RYR2) are noted in approximately 55% of the patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). However, a high background rate of rare amino acid-altering variants in RYR2 [≈3% (whites) to 6% (nonwhites)] in combination with delayed onset and variable expressivity of the CPVT phenotype make attributing causality to rare RYR2 variants difficult. The proposed set of guidelines for characterization of variants include, among many different criteria, functional studies to classify variants as pathogenic versus non- pathogenic. However, in vitro data, especially for complex channelopathies like CPVT, does not always correlate well with the human phenotype; therefore, characterizing the phenotypic features of rare RYR2 variants in humans is of importance. We report a 13-year-old carrier of a rare maternally inherited variant in exon 3 of RYR2 (p.Thr85Ile, c.254C>T [rs772005577]) who was successfully resuscitated from exercise-associated sudden cardiac arrest and was subsequently found to have exercise-induced complex ventricular ectopy. His brother, who has been asymptomatic, was also found to carry the same variant and demonstrated complex ventricular ectopy on exercise stress testing. These findings suggest that this rare variant, which has previously not been reported in patients with RYR2 related conditions, is associated with pathogenicity.

CHARGE syndrome: genetic aspects and dental challenges, a review and case presentation

BackgroundCHARGE syndrome (CS) is a rare genetic condition (OMIM #214800). The condition has a variable phenotypic expression. Historically, the diagnosis of CHARGE syndrome was based on the presence of specific clinical criteria. The genetic aetiology of CS has since been elucidated and attributed to pathogenic variation in the CHD7 gene (OMIM 608892) at chromosome locus 8q12.Case presentationA South African female of mixed ancestry heritage, aged 4 years, was referred for dental assessment to the Faculty of Dentistry, University of the Western Cape, in 2018. She had a diagnosis of CHARGE syndrome confirmed by a Medical Geneticist from the Division of Molecular Biology and Human Genetics at the University of Stellenbosch.The patient had a long prior history of health and developmental problems, with the correct diagnosis becoming apparent over time. She presented with many oral and craniofacial features warranting consideration by the dentist including micrognathia, hypoplastic nasal bones, cranial nerve dysfunction, bruxism, craniofacial anomalies and compromised sensory perception. The treatment was mainly preventive and, although she fed through a percutaneous endoscopic gastrostomy tube (PEG), maintenance of her oral hygiene was necessitated.Conclusion: CS is a multisystem condition and the optimal care for an individual is with a specialist multidisciplinary team. The numerous systemic problems affecting these individuals take precedence in their care, and often there is neglect of their dental concerns. Given the abnormalities frequently present in the oral and craniofacial region, the authors recommend that a team of dental and other medical specialists be involved in the management of individuals with CS.

Mandible customized distraction osteogenesis in Treacher Collins patient: Literature review, report of a case and post-distraction analysis

IntroductionTreacher-Collins syndrome is a rare genetic disorder with variable phenotypic expression. Related micrognathia can cause upper airway obstruction in neonatal patients because of posterior tongue displacement. Many approaches have been described to treat upper airway obstruction in such patients; the use of mandibular distraction to this purpose was first proposed in 1994. To our knowledge, only a few authors have employed customized devices to perform mandibular distraction in these syndromic patients.This paper presents a systematic review of the use of customized devices to perform mandibular distraction osteogenesis in patients affected by Treacher-Collins syndrome and upper airway obstruction. A case report of a Treacher-Collins syndrome patient treated in our institution is also presented. ResultsEight articles fulfilled the inclusion criteria and were included in this systematic review; demographic, clinical and surgical features of 13 cases were evaluated.Preoperative assessment, virtual surgical planning and a surgical protocol for a Treacher-Collins patient were performed and set-out in detail; a post-distraction 3D analysis workflow was developed and proposed.The patient had an airway obstruction resolution after the distractors removal and was progressively decannulated. The post-distraction 3D analysis revealed that the oropharynx and hypopharynx airway space acquired greater volumetric dimension in a more antero-superior position; this advancement was comparable to the antero-superior advancement of the distracted mandible. ConclusionIn the author’s opinion, customized devices for mandibular distraction osteogenesis and post-distraction tridimensional analysis should be objected of further investigation in the light of their potential advantage in diagnosis and treatment of syndromic malformation.

Tiered analysis of whole-exome sequencing for epilepsy diagnosis.

It is thought that despite highly variable phenotypic expression, 70-80% of all epileptic cases are caused by one or more genetic mutations. Next generation sequencing technologies, such as whole exome sequencing (WES), can be used in a diagnostic or research setting to identify genetic mutations which may have significant prognostic implications for patients and their families. In this study, 398 genes associated with epilepsy or recurrent seizures were stratified into tiers based on genotype-phenotype concordance, tissue gene expression, frequency of affected individuals with mutations and evidence from functional and family studies. WES was completed on 14 DNA samples (2 with known mutations in SCN1A and 12 with no known mutations) from individuals diagnosed with epilepsy using an Ion AmpliSeq approach. WES confirmed positive SCN1A mutations in two samples. In n = 5/12 samples (S-3 to -14) we identified potentially causative mutations across five different genes. S-5 was identified to have a novel missense mutation in CCM2; S-6 a novel frameshift mutation identified in ADGRV1; S-10 had a previously reported pathogenic mutation in PCDH19, whilst a novel missense mutation in PCDH19 was shown in S-12; and S-13 identified to have separate missense mutations in KCNA2 and NPRL3. The application of WES followed by a targeted variant prioritization approach allowed for the discovery of potentially causative mutations in our cohort of previously undiagnosed epilepsy patients.

APICAL VARIANT HYPERTROPHIC CARDIOMYOPATHY PRESENTS AS MID-CAVITARY HYPERTROPHIC CARDIOMYOPATHY WITH OBSTRUCTION 10 YEARS LATER

Apical variant hypertrophic cardiomyopathy (AHCM) is a rare genetic disease with variable phenotypic expression, typically associated with a benign prognosis. A 71-year-old female with AHCM presented with 3 days of exertional chest pain and was found to have NSTEMI. EKG showed deep T-wave

Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition

PurposeThe 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans, with highly variable phenotypic expression. Whereas congenital heart defects, palatal anomalies, immunodeficiency, hypoparathyroidism, and neuropsychiatric conditions are observed in over 50% of patients with 22q11DS, a subset of patients present with additional “atypical” findings such as craniosynostosis and anorectal malformations. Recently, pathogenic variants in the CDC45 (Cell Division Cycle protein 45) gene, located within the LCR22A–LCR22B region of chromosome 22q11.2, were noted to be involved in the pathogenesis of craniosynostosis. MethodsWe performed next-generation sequencing on DNA from 15 patients with 22q11.2DS and atypical phenotypic features such as craniosynostosis, short stature, skeletal differences, and anorectal malformations. ResultsWe identified four novel rare nonsynonymous variants in CDC45 in 5/15 patients with 22q11.2DS and craniosynostosis and/or other atypical findings. ConclusionThis study supports CDC45 as a causative gene in craniosynostosis, as well as a number of other anomalies. We suggest that this association results in a condition independent of Meier–Gorlin syndrome, perhaps representing a novel condition and/or a cause of features associated with Baller–Gerold syndrome. In addition, this work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to pathogenic variants on the nondeleted chromosome.

Agnathia-otocephaly complex: a case report and a literature review on recurrence risk

Abstract Objectives Agnathia-otocephaly complex (AOC) is an extremely rare, lethal disorder causing obstruction of the upper airway at birth due to absence of the mandible and hypoplasia of the oral cavity. Implications for future pregnancies need to be elucidated by parental counselling, as recurrence of AOC or associated comorbidities are possible. Very little is known on this subject, because of the rarity of the disorder and scarce data on genetic causes of this complex. The objectives of this study were to determine the recurrence risk and mode of inheritance for AOC based on current literature. Contents Recurrence of AOC or associated comorbidities within the family of an index case was reported in eight articles, describing 7 and 27 relatives, respectively. There were eight AOC cases in which the genetic cause was known. Mutations in 2 genes, orthodenticle homeobox 2 (OTX2) and paired related homeobox 1 (PRRX1), have been described. Due to its mainly sporadic appearance, recurrence risk is low. Counselling on recurrence risk is difficult, because of a broad heterogeneity with complex inheritance patterns and variability in phenotypic expression. Outlook Chromosomal analysis and exome sequencing in children with AOC will help unravel current aetiological uncertainties and could help in further reproductive decisions. We emphasize the need for timely diagnosis through ultrasound, providing parents with the opportunity to receive multidisciplinary counselling, giving them the chance to contemplate their management decisions.

Pediatric syndromes with noncraniofacial anomalies impacting the airways

Syndromes with noncraniofacial abnormalities can be a real challenge in terms of airway management. The key to success is effective preparation, presence of personnel with expertise in difficult pediatric airway management, regular training and familiarity with difficult intubation equipment, and teamwork. Considering that there are a very large number of syndromes, with variable phenotypic expression, the management strategy of every case will be dictated by the anatomical and functional airway as assessed on physical examination and subsidiary examinations before induction of anesthesia.

095 Characterising the Phenotypic Switch in a Murine Model of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) occurs due to mutations in sarcomeric proteins. At the cellular level, HCM characteristics include increased protein synthesis, increased mitochondrial number, altered cell metabolism and cardiomyocyte disorganisation. HCM has variable phenotypic expression and clinical characteristics often present later in life. Using a murine model of human HCM, we have shown that a mutation in cardiac troponin I (cTnI-G203S) is associated with cytoskeletal disorganisation and a hypermetabolic mitochondrial state. Alterations in metabolic activity precede manifestation of the HCM phenotype. However, little is known about the role of signalling pathways in disease progression. The mTOR signalling pathway is a key regulator of protein synthesis and cell metabolism, and may be involved in the development of HCM. Here we examined myocardial ultrastructure and cardiac mTOR signalling in cTnI-G203S mice. Studies were performed in mice before and after the development of HCM (pre- and post-HCM) using TEM and immunoblot methodologies. Pre-HCM cTnI-G203S hearts demonstrated an increasing trend in total and activated mTOR), and a significant increase in sarcomere area (p<0.001, n=2), versus age-matched wt hearts. Post-HCM cTnI-G203S hearts demonstrated (i) significantly higher total and activated mTOR (ptotal<0.05, n=3; pactivated: p<0.05, n=3), and (ii) a significant decrease in sarcomere area (p<0.001, n=2) versus age-matched wt hearts. We conclude that alterations in the mTOR signalling pathway may be involved in the progression of the HCM phenotype. Myocardial ultrastructure appears to alter as the phenotype develops from a pre- to post-cardiomyopathic state.

Dynamic thiol/disulphide homeostasis in patients with hypertrophic cardiomyopathy.

In addition to the genetic complexity of hypertrophic cardiomyopathy (HCM), there must be other disease-modifying factors that contribute to its highly variable clinical and phenotypic expression. The authors aimed to investigate serum thiol/disulphide homeostasis as aproxy for oxidative stress using anovel automated assay in patients with HCM. This cross-sectional study was conducted on 119 patients with HCM and 52 without HCM. The methods used to measure dynamic thiol/disulphide homeostasis as calorimetric and duplex quantities were developed in 2014. Median serum native thiol levels were significantly lower in patients with HCM than in those without (312.5 μmol/L [285-370 μmol/L] vs 421 μmol/L [349-469.5 μmol/L]; p < 0.001). Serum total thiol levels and disulphide levels were considerably lower than those in the control group ([844.68 ± 195.99 μmol/L vs 1158.92 ± 243.97 μmol/L; p < 0.001], [259.13 ± 65.66 μmol/L vs 375.02 ± 79.99 μmol/L; p < 0.001], respectively). Serum disulphide/native thiol ratios and disulphide/total thiol ratios were significantly lower in HCM patients than in controls (0.80 ± 0.09 vs 0.92 ± 0.05; p < 0.001 and 0.31 [0.30-0.32] vs 0.32 [0.32-0.33]; p < 0.001). Finally, reduced thiol ratios were higher and oxidized thiol ratios were significantly lower in patients with HCM than in controls. Despite the fact that antioxidant capacity was impaired, the extracellular environment remained in areducing state by keeping serum disulphide/native thiol ratios low. Therefore, the authors speculate that HCM may behave similarly to tumours with respect to serum thiol-disulphide levels.

Cutaneous neurofibromas: patients\u2019 medical burden, current management and therapeutic expectations: results from an online European patient community survey

BackgroundNeurofibromatosis type 1 is an inherited condition with variable phenotypic expression and a high medical and social burden.The objectives of this patient survey were to better understand the real-world experiences of patients living with cutaneous neurofibromas (cNF), to perceive their satisfaction and feelings about cNF current management (only laser and surgery are currently available), and to highlight their expectations of new therapeutic modalities.ResultsOne hundred seventy patients from 4 European countries took part in the study, 65% (n = 110) were women and mean age was 39 years old. 96% (n = 164) of respondents have cNF on visible parts of the body and the survey confirmed that total number of cNF and visibility increase with age.Patients reported that cNF mainly impacts everyday mood, general daily life and social life. The visibility of cNF had a higher impact than their number.92% (n = 156) of patients have a regular and multidisciplinary medical follow-up. The dermatologist is one of the most consulted healthcare professionals.76% (n = 130) of respondents have treated their cNF: 65% (n = 111) had surgery and 38% (n = 64) had multiple laser sessions. Frequency of operations and regrowth of cNF were the two most unsatisfactory aspects with both treatments for patients. Indeed, after removal, new cNF appear in more than 75% (n = 128) of cases.As a future treatment, patients expected a topical (30%, n = 51) or oral medication (29%, n = 50). Around 2 out of 3 patients would agree to take it at least once a day or more for life but they would like a well-tolerated treatment.According to patients, the most important effectiveness criteria of a new treatment are to block cNF growth and reduce their number. 70% (n = 119) of patients would consider a future treatment moderately effective to very effective if it could clear 30% of cNF.ConclusionsThis first cNF European patient community survey confirmed that the visible stigma and unaesthetic aspect of cNF have an important impact on patients’ quality of life. The survey highlighted that patients were not entirely satisfied with the actual surgery and laser treatments and revealed their clear and realistic expectations for future treatment of cNF.