Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

Recent advances in pathophysiology,diagnosis and management of hepatorenal syndrome:A review

Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.

Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder:A case report

BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.

Amniotic Band Syndrome at the Van Norman Clinic in Burundi: A Case Series

Amniotic band syndrome is an acquired embryo-fetopathy. It is rare and is characterized by malformations mainly affecting the limbs but also the skull, face and thoraco-abdominal axis. Its etiopathogenesis remains poorly understood. Its diagnosis is essentially clinical and is classically based on the existence of signs such as furrows, amputations and pseudosyndactyly. To show the importance of antenatal diagnosis in resource-limited countries, we report the case of two newborns, one premature at 31 weeks and the other at term, in whom amniotic band syndrome was discovered incidentally at birth. It involved an amputation of the right leg for both cases. The premature baby was born in a context of neonatal sepsis and will succumb to the latter while the 2nd case was released from the hospital alive. Imaging examinations to search for probable congenital malformations could only be carried out for the 2nd case and no accessible congenital malformation had been identified. And as management of the disease, only psychological support to the parents was provided for the 2 cases. The antenatal discovery of a case of amniotic band syndrome in countries with low technical capacity such as Burundi should push clinicians to think in time about treatment options.

Incidental Finding of Pyeloureteral Junction Syndrome during Extension Workup for Prostatic Adenocarcinoma

Introduction: Prostate cancer is one of the most common cancers in men. In cases of suspected locally advanced disease or lymph node or bone metastases, thoraco-abdomino-pelvic CT is still useful for detecting visceral metastases. In the course of this extension work-up, other abnormalities may be discovered by chance, which had previously remained silent, and which could be diagnosed and managed in childhood, hence the interest of presenting a case of incidental finding of pyeloureteral junction syndrome during extension workup for prostatic adenocarcinoma at Yaounde Central Hospital. Observation: A 72-year-old patient presented to the department with acute urinary retention. The clinical examination, with an empty bladder, and in particular the digital rectal exam (DRE), was in favor of malignant prostatic hypertrophy. A workup was ordered, including a total PSA returned to 61.3 ng/ml (PSA performed one week after the episode of acute urinary retention) with cytobacteriological examination of sterile urine. Renal function was slightly impaired, with creatinemia at 14 ng/ml. Renal and vesico-prostatic ultrasound revealed a 57 g prostate with regular, clean contours and a polycystic right kidney. A prostate biopsy was indicated, which revealed a histopathological aspect in favor of a prostatic adenocarcinoma ISUP 1. An extension work-up including a thoraco-abdomino-pelvic CT scan revealed no signs of local or distant secondary localization, but a pyeloureteral junction syndrome with significant hydronephrosis, parenchymal destruction and compensatory hypertrophy of the contralateral kidney was found. Conclusion: The prostate cancer extension work-up revealed a pathology that can be diagnosed early. It is therefore important to reinforce prenatal and natal screening, which will enable malformative uropathies to be identified early and corrected in time to preserve patients’ renal function. Furthermore, we must be careful in the ultrasound diagnosis of pyeloureteral junction syndrome.

Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.

Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy

Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.

Budd-Chiari syndrome:Etiology,pathogenesis and diagnosis

Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.

Diagnosis and Management of Severe Acute Pancreatitis Complicated with Abdominal Compartment Syndrome

Presented in this paper is our experience in the diagnosis and management of abdominal compartment syndrome during severe acute pancreatitis. On the basis of the history of severe acute pancreatitis, after effective fluid resuscitation, if patients developed renal, pulmonary and cardiac insufficiency after abdominal expansion and abdominal wall tension, ACS should be considered. Cystometry could be performed to confirm the diagnosis. Emergency decompressive celiotomy and temporary abdominal closure with a 3 liter sterile plastic bag must be performed. It is also critical to prevent reperfusion syndrome. In 23 cases of ACS, 18 cases received emergency decompressive celiotomy and 5 cases did not. In the former, 3 patients died (16.7 %) while in the later, 4 (80%) died. Total mortality rate was 33.3% (7/21). In 7 death cases, 4 patients developed acute obstructive suppurative cholangitis (AOSC). All the patients who received emergency decompressive celiotomy 5 h after confirmation of ACS survived. The definitive abdominal closure took place mostly 3 to 5 days after emergency decompressive celiotomy, with longest time being 8 days. 6 cases of ACS at infection stage were all attributed to infected necrosis in abdominal cavity and retroperitoneum. ACS could occur in SIRS stage and infection stage during SAP, and has different pathophysiological basis. Early diagnosis, emergency decompressive celiotomy and temporary abdominal closure with a 3L sterile plastic bag are the keys to the management of the condition.

Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea

AIM: To validate 4-sample lactose hydrogen breath testing(4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea(IBS-D) and healthy volunteers(HVs) were enrolled and received a 10 g, 20 g, or 40 g doselactose hydrogen breath test(LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h(13 measurements). The detection rates of lactose malabsorption(LM) and lactose intolerance(LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups(P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT(97%-100%, Kappa 0.815-0.942) with high sensitivity(90%-100%) and specificity(100%) at all three lactose doses in both groups.CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.

Solitary rectal ulcer syndrome:Clinical features,pathophysiology,diagnosis and treatment strategies

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differ-entiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Expert consensus on the diagnosis and treatment of myofascial pain syndrome

Myofascial pain syndrome(MPS)is characterized by myofascial trigger points and fascial constrictions.At present,domestic and foreign scholars have not reached a consensus on the etiology and pathogenesis of MPS.Due to the lack of specific laboratory indicators and imaging evidence,there is no unified diagnostic criteria for MPS,making it easy to confuse with other diseases.The Chinese Association for the Study of Pain organized domestic experts to formulate this Chinese Pain Specialist Consensus on the diagnosis and treatment of MPS.This article reviews relevant domestic and foreign literature on the definition,epidemiology,pathogenesis,clinical manifestation,diagnostic criteria and treatments of MPS.The consensus is intended to normalize the diagnosis and treatment of MPS and be used by first-line doctors,including pain physicians to manage patients with MPS.

A handy review of carpal tunnel syndrome:From anatomy to diagnosis and treatment

Carpal tunnel syndrome(CTS) is the most commonly diagnosed disabling condition of the upper extremities. It is the most commonly known and prevalent type of peripheral entrapment neuropathy that accounts for about 90% of all entrapment neuropathies. This review aims to provide an outline of CTS by considering anat-omy, pathophysiology, clinical manifestation, diagnostic modalities and management of this common condition, with an emphasis on the diagnostic imaging evaluation.

Diagnosis and management of postural orthostatic tachycardia syndrome：A brief review

Postural orthostatic tachycardia syndrome （POTS） has been recognized since at least 1940.A review of the literature identifies differences in the definition for this condition and wide variations in treatment and outcomes.This syndrome appears to describe a group of conditions with differing pathophysiology,which requires treatment tailored to the true underlying disorder.Patients need to be fully evaluated to guide treatment.Further research is required to effectively classify the range of underlying pathophysioiogy that can produce this syndrome and to guide optimal management.

Diagnosis of Laron syndrome using monoplex-polymerase chain reaction technology with a whole-genome amplification template: A case report

BACKGROUND Laron syndrome(LS)is an autosomal recessive hereditary condition affecting only 1/1000000 births.The cause is associated with mutations in the growth hormone(GH)receptor(GHR),leading to GH insensitivity.LS patients typically present with severe growth retardation,obesity,and abnormal sexual maturation.Currently,LS diagnosis is performed post-delivery.Therefore,we assessed the efficiency of Pre-implantation Genetic Testing(PGT)coupled with monoplex-polymerase chain reaction(PCR)technology for detecting this monogenic disease in embryos from a couple confirmed as LS heterozygous carriers CASE SUMMARY The couple LS-carriers were confirmed by the presence of a first child born with LS.The couple underwent a standard in vitro fertilization(IVF)protocol.DNA was collected from trophectoderm cells from day 5 embryos.Whole genome amplification(WGA)was performed using a Sureplex DNA Amplification System and analyzed by PCR,targeting the deletion of the exons 5 and 6 in the GHR gene as well as PGT by Next-generation Sequencing(Illumina).Eleven embryos were collected and analyzed.27.3%were the wild type for GHR,45.5%were heterozygotes,and 18.2%homozygous mutants.One embryo yielded no results.Three 2-embryos transfers were performed;2 normal homozygous and four heterozygous carriers were selected for transfer.The first two transfers were unsuccessful,whereas the final transfer with two heterozygous embryos resulted in clinical pregnancy.The genomic composition of the fetus was verified,applying the same techniques using amniocytes,extracted after 21 wk of the ongoing pregnancy.The fetus was confirmed as GHR deletion in exon 5-6,carrier.A non-affected baby was born.CONCLUSION Here,we present a case demonstrating that using WGA as a template in addition to PCR targeting specific gene regions,exons 5 and 6 on the GHR gene,could identify LS carrier embryos.This provides evidence that WGA and PCR serve as an excellent tool to detect this specific monogenic disease in IVF embryos,thus allowing selection of candidate embryos for transfer successfully when a specific inherited genetic mutation/disease is suspected.

Perceived risk as a barrier to appropriate diagnosis of irritable bowel syndrome

AIM: To evaluate perceived risk, diagnostic testing, and acceptance of a diagnosis of irritable bowel syndrome (IBS) among the Korean laypersons.

Hepatorenal syndrome: Update on diagnosis and treatment

Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.

Diagnosis and management of severe Budd-Chiari syndrome

OBJECTIVE: To assess the diagnostic standards and treatment of severe Budd-Chiari syndrome (BCS).METHODS: The clinical data of 126 patients with severe BCS treated from November 1994 to June 2001at our hospital were retrospectively analyzed. Percutaneous transhepatic recanalization and dilation and/orstent placement of the main hepatic vein was performed in 10 patients. Mesocaval C type shunt withartificial graft was performed in 68 patients, splenojugular shunt in 33, mesojuglar shunt in 1, andmesocaval shunt or improved splenopneumopexy after percutaneous intraluminal angioplasty and stentplacement of the inferior vena cava in 14.RESULT: Six patients died during perioperation. In 120 patients followed up for 6 months to 7 years, 89had excellent results and 31 good results.CONCLUSIONS: Diagnostic standards of severe BCS are suggested. Proper treatment should be usedaccording to the pathological changes of the inferior vena cava and main hepatic veins.

Preimplantation genetic diagnosis for Down syndrome pregnancy

Objective: To evaluate the effect of preimplantation genetic diagnosis (PGD) conducted for women who had Down syndrome pregnancy previously. Methods: Trisomy 21 was diagnosed by using fluorescence in site hybridization (FISH) before embryo transfer in two women who had Down syndrome pregnancies. Each received one or two PGD cycles respectively. Results: Case 1: one PGD cycle was conducted, two oocytes were fertilized and biopsied. One embryo is of trisomy 21 and the other of monosomy 21. No embryo was transferred. Case 2: two PGD cycles were conducted, in total, sixteen oocytes were fertilized and biopsied. Four embryos were tested to be normal, six of trisomy 21, and one of monosomy 21. Five had no signal. Four normal embryos were transferred but no pregnancy resulted. Conclusion: For couples who had pregnancies with Down syndrome pre-viously, PGD can be considered, and has been shown to be an effective strategy.

ANTENATAL DIAGNOSIS AND MANAGEMENT OF DANDY-WALKER SYNDROME

The Dandy-Walker syndrome (DWS) can be accurately diagnosed in utero by sonographic demonstration of characteristic morphologic changes of the fetus, which includes hydrocephalus, incomplete cerebellar vermis and a posterior fossa cyst. We present a case of Dandy-Walker syndrome diagnosed antenatally. The assoiacted anomalies are reviewed, and the value of antenatal diagnosis is discussed.