ABSTRACT
Esophagogastroduodenoscopy (EGD) is recommended in patients with typical gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation, chest pain) in the setting of proton pump inhibitor (PPI) nonresponse. EGD evaluates for erosive disease, assesses antireflux barrier integrity, excludes non-GERD conditions, and, in the absence of erosive findings, is followed by reflux testing.1,2 The diagnostic utility of EGD is less clear in the evaluation for laryngopharyngeal reflux (LPR), and the current reference standard is ambulatory reflux monitoring.1,3,4 This study of patients referred for evaluation of chronic laryngeal symptoms had the following aims: (1) to characterize endoscopic findings, (2) to discern whether findings differed between patients with or without concomitant esophageal reflux symptoms, and (3) to measure the association between endoscopic findings and objective GERD on ambulatory reflux monitoring.
Subject(s)
Laryngopharyngeal Reflux , Humans , Laryngopharyngeal Reflux/diagnosis , Female , Male , Middle Aged , Adult , Aged , Endoscopy, Digestive System/methodsABSTRACT
BACKGROUND & AIMS: Cognitive-affective processes, including hypervigilance and symptom-specific anxiety, may contribute to chronic laryngeal symptoms and are potentially modifiable; however, a validated instrument to assess these constructs is lacking. The aims of this study were to develop and validate the Laryngeal Cognitive-Affective Tool (LCAT) instrument. METHODS: This 2-phase single-center prospective study enrolled participants from November 2021 to June 2023. In the initial phase 1:1 patient cognitive interviews and multidisciplinary team consensus were conducted to develop the LCAT. In the second phase asymptomatic and symptomatic participants completed a series of questionnaires to examine psychometric properties of the LCAT. RESULTS: A total of 268 participants were included: 8 in the initial phase and 260 in the validation phase (56 asymptomatic; 204 symptomatic). A 15-item LCAT was developed. In the validation phase, mean total LCAT and hypervigilance/anxiety subscores were significantly higher in symptomatic versus asymptomatic participants (P < .01). The LCAT had excellent internal consistency (α = 0.942) and split-half reliability (Guttman = 0.853). Using a median split, a score of 33 or greater was defined as elevated. CONCLUSIONS: The 15-item LCAT evaluates laryngeal hypervigilance and symptom-specific anxiety among patients with laryngeal symptoms. It has excellent reliability and construct validity. The LCAT highlights burdensome cognitive-affective processes that can accordingly help tailor treatments.
Subject(s)
Psychometrics , Humans , Male , Female , Middle Aged , Prospective Studies , Surveys and Questionnaires , Aged , Adult , Psychometrics/methods , Reproducibility of Results , Anxiety/diagnosis , Laryngeal Diseases/diagnosis , Laryngeal Diseases/psychology , Cognition/physiologyABSTRACT
BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and ß coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. RESULTS: A total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD. CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.
Subject(s)
Cough , Gastroesophageal Reflux , Humans , Male , Female , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/complications , Middle Aged , Cough/etiology , Adult , Chronic Disease , Aged , ROC Curve , Laryngeal Diseases/diagnosis , Laryngeal Diseases/complicationsABSTRACT
INTRODUCTION: Laryngopharyngeal symptoms such as cough, throat clearing, voice change, paradoxic vocal fold movement, or laryngospasm are hyper-responsive behaviors resulting from local irritation (e.g., refluxate) and heightened sympathetic tone. Laryngeal recalibration therapy (LRT) guided by a speech-language pathologist (SLP) provides mechanical desensitization and cognitive recalibration to suppress hyper-responsive laryngeal patterns. The aim of this study was to assess symptom response to LRT among patients with chronic laryngopharyngeal symptoms undergoing evaluation of gastroesophageal reflux disease (GERD). METHODS: Adults with chronic laryngopharyngeal symptoms referred for evaluation of GERD to a single center were prospectively followed. Inclusion criteria included ≥2 SLP-directed LRT sessions. Data from endoscopy, ambulatory reflux monitoring, and patient-reported outcomes were collected when available. The primary outcome was symptom response. RESULTS: Sixty-five participants completed LRT: mean age 55.4 years (SD 17.2), 46 (71%) female, mean body mass index 25.6 kg/m 2 (6.8), and mean of 3.7 (1.9) LRT sessions. Overall, 55 participants (85%) met criteria for symptom response. Specifically, symptom response was similar between those with isolated laryngopharyngeal symptoms (13/15, 87%) and concomitant laryngopharyngeal/esophageal symptoms (42/50, 84%). Among participants who underwent reflux monitoring, symptom response was similar between those with proven, inconclusive for, and no GERD (18/21 [86%], 8/9 [89%], 10/13 [77%]). DISCUSSION: Eighty-five percent of patients with chronic laryngopharyngeal symptoms referred for GERD evaluation who underwent LRT-experienced laryngeal symptom response. Rates of symptom response were maintained across patients with or without proven GERD and patients with or without concomitant esophageal reflux symptoms. SLP-directed LRT is an effective approach to incorporate into multidisciplinary management of chronic laryngopharyngeal symptoms/laryngopharyngeal reflux disease.
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Bile acids in refluxate contribute to esophageal and laryngeal symptoms and are quantifiable. The aim of this study was to compare salivary bile acid concentrations across healthy controls and symptomatic patients (esophageal or laryngeal) with or without objective gastroesophageal reflux disease (GERD). This prospective study enrolled adults into three groups: esophageal symptoms (heartburn, regurgitation, chest pain); laryngeal symptoms (cough, throat clearing, sore throat, dysphonia); and controls. Symptomatic patients primarily underwent prolonged wireless reflux monitoring off acid suppression and were categorized as symptomatic no GERD (acid exposure time <4%) or esophageal/laryngeal symptoms with GERD (acid exposure time ≥4%). Controls did not undergo reflux monitoring nor upper endoscopy. Saliva samples were provided for bile acid analysis via ultraperformance liquid chromatography tandem mass spectrometry. Thirty-five participants were enrolled (mean age 47.4 years [SD 18.9], 16 [46%] male), including 10 controls and 25 symptomatic: 9 no GERD, 5 esophageal symptoms + GERD, and 11 laryngeal symptoms + GERD. Total salivary bile acids were highest in the laryngeal symptoms + GERD group (24.2 nM [SD 24.7]) compared to other groups (controls: 5.8 [6.0], P = 0.03; symptomatic no GERD: 3.1 [4.4]; P < 0.01; esophageal symptoms + GERD: 7.1 [7.1], P = 0.10). Bile acids were elevated in 45% (5/11) of the laryngeal symptoms + GERD group compared to 0% of the other three groups (P < 0.01). Salivary bile acids were higher among patients with laryngeal symptoms and objective GERD versus other groups. Salivary bile acids are a quantifiable biomarker with diagnostic potential for laryngopharyngeal reflux.
Subject(s)
Bile Acids and Salts , Biomarkers , Laryngopharyngeal Reflux , Saliva , Humans , Bile Acids and Salts/analysis , Bile Acids and Salts/metabolism , Male , Female , Middle Aged , Biomarkers/analysis , Biomarkers/metabolism , Pilot Projects , Saliva/chemistry , Saliva/metabolism , Prospective Studies , Laryngopharyngeal Reflux/diagnosis , Laryngopharyngeal Reflux/metabolism , Adult , Case-Control Studies , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/metabolism , AgedABSTRACT
Previous research has identified an increase in internalizing problems during the COVID-19 pandemic in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Additionally, it has been observed that parents of children with ADHD had elevated levels of anxiety during the pandemic. The current study aimed to longitudinally assess whether the impact of COVID-19 was associated with internalizing problems in children and adolescents with ADHD during the middle (Time 1-Spring 2021 [T1]) and end (Time 2-Fall/Winter 2022 [T2]) of the pandemic, and whether parental anxiety moderated this relationship over time. Canadian parents of youth with ADHD (aged 3-18 years old) completed online questionnaires assessing their child's depression and anxiety symptoms, their own anxiety symptoms, and the pandemic's impact on their child, both at T1 (N = 278) and T2 (N = 89). The results indicated that the impact of COVID-19 on children at T1 was a unique predictor of child internalizing problems at T1 but not at T2. While parental anxiety did not moderate this association cross-sectionally, it was a significant moderator longitudinally. More specifically, low parental anxiety at T1 positively moderated the association between the COVID-19 impact on children at T1 and child internalizing problems at T2. The results highlight the importance of providing on-going psychological support for children and adolescents with ADHD and emphasize the need to aid parents in effectively supporting their children during the process of pandemic recovery.
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BACKGROUND: Laryngopharyngeal reflux has classically referred to gastroesophageal reflux leading to chronic laryngeal symptoms such as throat clearing, dysphonia, cough, globus sensation, sore throat or mucus in the throat. Current lack of clear diagnostic criteria significantly impairs practitioners' ability to identify and manage laryngopharyngeal reflux. AIMS: To discuss current evidence-based diagnostic and management strategies in patients with laryngopharyngeal reflux. METHODS: We selected studies primarily based on current guidelines for gastroesophageal reflux disease and laryngopharyngeal reflux, and through PubMed searches. RESULTS: We assess the current diagnostic modalities that can be used to determine if laryngopharyngeal reflux is the cause of a patient's laryngeal symptoms, as well as review some of the common treatments that have been used for these patients. In addition, we note that the lack of a clear diagnostic gold-standard, as well as specific diagnostic criteria, significantly limit clinicians' ability to determine adequate therapies for these patients. Finally, we identify areas of future research that are needed to better manage these patients. CONCLUSIONS: Patients with chronic laryngeal symptoms are complex due to the heterogenous nature of symptom pathology, inconsistent definitions and variable response to therapies. Further outcomes data are critically needed to help elucidate ideal diagnostic workup and therapeutic management for these challenging patients.
Subject(s)
Esophagitis, Peptic , Laryngopharyngeal Reflux , Humans , Laryngopharyngeal Reflux/diagnosis , Laryngopharyngeal Reflux/therapyABSTRACT
OBJECTIVE: There exists a paucity of data regarding the mechanism and manometric findings in retrograde cricopharyngeal dysfunction (RCPD). In this study, we aimed to compare esophageal physiologic findings between patients with RCPD compared to an asymptomatic cohort. STUDY DESIGN: Case-control study. SETTING: Tertiary Care Center. METHODS: Esophageal high-resolution impedance manometry was completed preoperatively in patients diagnosed with RCPD. Manometric data were compared between the RCPD and asymptomatic cohorts. A 2:1 age-sex-matched asymptomatic cohort was used as the control group. Treatment response was assessed among the RCPD cohort. RESULTS: Thirty-nine patients are included: 13 RCPD [mean age: 31.1 (SD: 12.6) years, female sex: 11 (85%)] and 26 asymptomatic [mean age: 32.1 (SD: 1.5) years, female sex: 22 (85%)]. The RCPD cohort, compared to the asymptomatic cohort, exhibited significantly greater upper esophageal sphincter (UES) length [4.5 (SD: 0.7) vs 3.7 (0.9) cm, P = .01] and higher UES basal pressures [91.9 (35.0) vs 49.7 (25.5) mm Hg, P = .002]. Patients with RCPD demonstrated higher rates of ineffective swallows [70.0% (31.6%) vs 15.4% (21.6%), P < .001] and incomplete bolus clearance [81% (22.0%) vs 21.8% (30.0%), P < .001]. All patients who underwent cricopharyngeal botulinum injections experienced initial improvement of symptoms with 3 patients requiring repeat intervention. CONCLUSION: RCPD is associated with a longer UES, elevated UES basal pressures, and an increased incidence of ineffective esophageal motility. This study is the first to compare preoperative manometry results among patients with RCPD to those of an asymptomatic cohort, providing insights into the mechanism of RCPD.
Subject(s)
Esophageal Motility Disorders , Esophageal Sphincter, Upper , Manometry , Humans , Female , Manometry/methods , Esophageal Sphincter, Upper/physiopathology , Male , Case-Control Studies , Adult , Esophageal Motility Disorders/physiopathology , Esophageal Motility Disorders/diagnosis , Deglutition Disorders/physiopathology , Middle AgedABSTRACT
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition with complete age-dependent penetrance, variable expressivity and a global prevalence of â¼1/3,000. It is characteriszed by numerous café-au-lait macules, skin freckling in the inguinal or axillary regions, Lisch nodules of the iris, optic gliomas, neurofibromas, and tumour predisposition. The diagnostic testing strategy for NF1 includes testing for DNA single nucleotide variants (SNVs), copy number variants (CNVs) as well as RNA analysis for deep intronic and splice variants, which can cumulatively identify the causative variant in 95% of patients. In the present study, NF1 patients were screened using a next-generation sequencing (NGS) assay targeting NF1 exons and intron/exon boundaries for SNV and NF1 multiple ligation-dependent probe amplification (MLPA) analysis for CNV detection. Twenty-six unrelated Southern African patients clinically suspected of having NF1, based on the clinical diagnostic criteria developed by the National Institute of Health (NIH), were included in the current study. A detection rate of 58% (15/26) was obtained, with SNVs identified in 80% (12/15) using a targeted gene panel and NF1 gene deletion in 20% (3/15) identified using MLPA. Ten patients (38%) had no variants identified, although they met NF1 diagnostic criteria. One VUS was identified in this study in a patient that met NF1 diagnostic criteria, however there was no sufficient information to classify variant as pathogenic. The clinical features of Southern African patients with NF1 are similar to that of the known NF1 phenotype, with the exception of a lower frequency of plexiform neurofibromas and a higher frequency of developmental/intellectual disability compared to other cohorts. This is the first clinical and molecular characterisation of a Southern African ancestry NF1 cohort using both next-generation sequencing and MLPA analysis. A significant number of patients remained without a diagnosis following DNA-level testing. The current study offers a potential molecular testing strategy for our low resource environment that could benefit a significant proportion of patients who previously only received a clinical diagnosis without molecular confirmation.
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BACKGROUND: Huntington disease-like 2 (HDL2) is a neurodegenerative disorder, affecting only individuals of African ancestry. Full penetrance occurs in individuals with 40 repeats or more. OBJECTIVE: To describe the phenotypic variability of HDL2 in a group of mixed ancestry individuals from South Africa. METHODS: Eight patients were assessed with analysis of repeat size and magnetic resonance brain imaging. We applied the Unified Huntington's Disease Rating Scale (UHDRS), but in deceased patients (4), this was estimated from video material. RESULTS: Cognitive domains were more severely affected than motor; UHDRS motor scores were notable for bradykinesia, and to a slightly lesser extent, for rigidity and dystonia; a single patient had marked chorea. Repeat lengths ranged from 45 to 63 (median, 52). CONCLUSION: This South African group of mixed ancestry HDL2 individuals presented with severe cognitive and behavioral impairments, with lesser degrees or absence of chorea. This presentation is possibly related to large repeat sizes.
Subject(s)
Magnetic Resonance Imaging , Humans , Male , South Africa/epidemiology , Female , Middle Aged , Adult , Black People/genetics , Huntington Disease/genetics , Huntington Disease/diagnosis , Huntington Disease/ethnology , Aged , Heredodegenerative Disorders, Nervous System/genetics , Heredodegenerative Disorders, Nervous System/diagnosis , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Brain/pathology , Brain/diagnostic imaging , Chorea/genetics , Chorea/diagnosis , Cognition Disorders , DementiaABSTRACT
BACKGROUND: Patients with chronic laryngopharyngeal symptoms, with or without pathologic reflux, frequently have poor response to standard therapies, which may be a result of overlapping cognitive-affective processes. Therefore, the aims of this study included measuring psychosocial distress and laryngeal-specific cognitive distress in patients with chronic laryngopharyngeal symptoms (LPS) as well as comparing these among laryngeal symptomatic patients with and without conclusive gastroesophageal reflux disease (GERD). METHODS: This prospective, single-center study enrolled adults with chronic LPS from 9/22 to 6/23. Patients completed eight questionnaires on quality of life, symptom burden, and psychosocial distress. The laryngeal cognitive affective tool (LCAT) assessed laryngeal-specific hypervigilance and anxiety; LCAT scores ≥33 were elevated. All patients underwent objective testing with endoscopy and/or ambulatory reflux monitoring and were categorized as proven GERD (GER+) or no proven GERD (GER-). KEY RESULTS: One hundred twenty-nine patients were included: 66% female, mean age 54.1 (17.5) years, mean BMI 27.6 (6.8) kg/m2, 66% Caucasian, 57% with an elevated LCAT, and 53% GER+. Moderate-to-severe anxiety was found in 39% and moderate-to-severe depression in 19%. An elevated LCAT alone or with an elevated anxiety/depression score was found in 58%. Patient-reported outcomes scores, including LCAT scores (32.9 (13.8) GER- vs. 33.1 (12.6) GER+, p = 0.91), were similar between patients with and without GER+. CONCLUSIONS AND INFERENCES: Patients with chronic LPS experience heightened levels of hypervigilance, symptom-specific anxiety, and psychosocial distress, regardless of the presence of pathologic GER.
Subject(s)
Gastroesophageal Reflux , Quality of Life , Humans , Female , Male , Middle Aged , Gastroesophageal Reflux/psychology , Prospective Studies , Adult , Aged , Quality of Life/psychology , Chronic Disease , Laryngopharyngeal Reflux/psychology , Anxiety/psychology , Surveys and Questionnaires , Psychological DistressABSTRACT
Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation. Nevertheless, outside South Africa, reports of patients with HDL2 in Africa are scarce, probably owing to limited clinical services across the continent. Systematic comparisons of HDL2 and HD have revealed closely overlapping motor, cognitive and psychiatric features and similar patterns of cerebral and striatal atrophy. The pathogenesis of HDL2 remains unclear but it is proposed to occur through several mechanisms, including loss of protein function and RNA and/or protein toxicity. This Review summarizes our current knowledge of this African-specific HD phenocopy and highlights key areas of overlap between HDL2 and HD. Given the aforementioned similarities in clinical phenotype and pathology, an improved understanding of HDL2 could provide novel insights into HD and other neurodegenerative and/or trinucleotide repeat expansion disorders.
Subject(s)
Chorea , Cognition Disorders , Dementia , Huntington Disease , Humans , Huntington Disease/metabolism , Chorea/complications , Chorea/genetics , Chorea/pathology , Dementia/genetics , Cognition Disorders/pathologyABSTRACT
BACKGROUND: Cornelia de Lange Syndrome (CdLS) presents with a variable multi-systemic phenotype and pathogenic variants have been identified in five main genes. This condition has been understudied in African populations with little phenotypic and molecular information available. METHODS AND RESULTS: We present a cohort of 14 patients with clinical features suggestive of CdLS. Clinical phenotyping was carried out and cases were classified according to the international consensus criteria. According to this criteria, nine patients had classical CdLS, one had non-classical CdLS and four presented with a phenotype that suggested molecular testing for CdLS. Each patient underwent mutation profiling using a targeted next generation sequencing panel of 18 genes comprising known and suspected CdLS causal genes. Of the 14 patients tested, pathogenic and likely pathogenic variants were identified in nine: eight variants in the NIPBL gene and one in the STAG1 gene. CONCLUSIONS: We present the first molecular data for a cohort of South African patients with CdLS. Eight of the nine variants identified were in the NIPBL gene, the most commonly involved gene in cases of CdLS. This is also the first report of a patient of African ancestry presenting with STAG1-related CdLS.
Subject(s)
Cell Cycle Proteins , De Lange Syndrome , Humans , Cell Cycle Proteins/genetics , De Lange Syndrome/genetics , De Lange Syndrome/pathology , South Africa , Mutation , PhenotypeABSTRACT
Background: Huntington's disease like 2 (HDL2) has been reported exclusively in patients with African ancestry, mostly originating from South Africa. Case report: We report three patients in Mali including a proband and his two children who have been examined by neurologists and psychiatrists after giving consent. They were aged between 28 and 56 years old. Psychiatric symptoms were predominant in the two younger patients while the father presented mainly with motor symptoms. Genetic testing identified a heterozygous 40 CTG repeat expansion in the Junctophilin-3 (JPH3) gene in all three patients. Discussion: This study supports the hypothesis that HDL2 may be widely spread across Africa. Highlights: We report here the first case of HDL2 in West Africa, suggesting that HDL2 is widely spread across African continent, and increasing access to genetic testing could uncover other cases.
Subject(s)
Huntington Disease , Child , Humans , Adult , Middle Aged , Mali , Huntington Disease/genetics , Family , Genetic Testing , HeterozygoteABSTRACT
STAC3 disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A STAC3 c.851 G > C (p.Trp284Ser) pathogenic variant, common in the Lumbee Native American tribe, has been identified in other populations worldwide, including patients of African ancestry. We report on the frequency of STAC3 c.851 G > C in a cohort of 127 patients presenting with congenital hypotonia that tested negative for spinal muscular atrophy and/or Prader-Willi syndrome. We present a clinical retrospective, descriptive review on 31 Southern African patients homozygous for STAC3 c.851 G > C. The frequencies of various phenotypic characteristics were calculated. In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3 c.851 G > C. A carrier rate of 1/56 and a predicted birth rate of 1/12 500 was estimated from a healthy cohort. A common haplotype spanning STAC3 was identified in four patients. Of the clinical group, 93% had a palatal abnormality, 52% a spinal anomaly, 59% had talipes equinovarus deformity/deformities, 38% had arthrogryposis multiplex congenita, and 22% had a history suggestive of malignant hyperthermia. The novel finding that STAC3 disorder is a common African myopathy has important clinical implications for the diagnosis, treatment and genetic counselling of individuals, with neonatal and/or childhood hypotonia with or without arthrogryposis multiplex congenita, and their families. The spread of this variant worldwide and the allele frequency higher in the African/African-American ancestry than the Admixed Americans, strongly indicates that the STAC3 c.851 G > C variant has an African origin which may be due to an ancient mutation with migration and population bottlenecks.
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Structural variants are responsible for a large part of genomic variation between individuals and play a role in both common and rare diseases. Databases cataloguing structural variants notably do not represent the full spectrum of global diversity, particularly missing information from most African populations. To address this representation gap, we analysed 1,091 high-coverage African genomes, 545 of which are public data sets, and 546 which have been analysed for structural variants for the first time. Variants were called using five different tools and datasets merged and jointly called using SURVIVOR. We identified 67,795 structural variants throughout the genome, with 10,421 genes having at least one variant. Using a conservative overlap in merged data, 6,414 of the structural variants (9.5%) are novel compared to the Database of Genomic Variants. This study contributes to knowledge of the landscape of structural variant diversity in Africa and presents a reliable dataset for potential applications in population genetics and health-related research.
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Background: Although cystic fibrosis (CF) is a common genetic condition; genetic counselling services appear to be underutilised by affected families. The aim of this study was to determine the uptake of genetic counselling and mutation testing for CF by relatives of affected individuals; and the impact of introducing hospital-based genetic counselling services.Method: The files of 153 families seen for genetic counselling for CF by staff of the Division of Human Genetics; School of Pathology; University of the Witwatersrand; and the National Health Laboratory Service (NHLS) in Johannesburg; were retrospectively reviewed from 1990 to 2006; the year when hospital-based genetic counselling services were introduced.Results: Parents of CF probands were the largest single group (35) of counsellees. Most individuals (66) attended genetic counselling to gather information. Most had been referred by medical specialists (56). Only 10 of referrals originated from general practitioners. On average; from 1990-2005; six families received genetic counselling annually; whereas in 2006; 58 families were seen. In 140 unrelated families; 1 991 relatives with carrier risks of ? 25 were identified. Only 11of these relatives underwent mutation testing; and eight per cent received genetic counselling through our division over the review period.Conclusion: Overall; referrals of family members (of affected CF individuals) to genetic counselling; by general practitioners; are poor. Uptake of genetic counselling services is greater when such services are integrated into hospital-based CF management clinics; than when offered elsewhere. The low uptake of mutation testing and genetic counselling by at-risk relatives is a concern; since these relatives are at high risk of having affected children; if their partners are CF carriers. Education of affected individuals; their close relatives; and medical practitioners; should be prioritised. This will ensure referral to genetic counselling for discussion about the risks of and available testing for CF; and other genetic conditions