Polycystic Liver Disease: A Case Report

Polycystic liver disease is characterized by multiple cystic lesions on the liver. Liver cysts are typically incidental findings, with occasional complications including cyst hemorrhage, infection and rupture. Polycystic liver disease may be part of autosomal dominant polycystic liver disease (ADPLD). Autosomal dominant polycystic liver disease is considered rare autosomal dominant disease, with prevalence of 1/100,000-1,000,000. Without family history of polycystic liver disease, ADPLD is defined as the presence of more than 20 liver cysts with no renal cysts, however up to third of ADPLD may have small number of renal cysts without kidney function impairment. This case of a 73-year-old woman with symptomatic polycystic liver disease, and we performed cyst fenestration-deroofing via laparoscopic.

Impact of lanadelumab in hereditary angioedema: a case series of 12 patients in Canada

Background Hereditary angioedema (HAE) is a rare autosomal dominant disease resulting in recurring episodes of swelling, leading to considerable patient morbidity and mortality. Lanadelumab is a plasma kallikrein inhibitor that is approved as 1st line therapy in Canada for long term prophylaxis of HAE attacks. Objective To describe our clinical findings from a case series of adult patients with HAE type 1/2 who have been initiated on lanadelumab. Methods A chart review of HAE type 1/2 patients at three academic centers in Canada was undertaken with demographic and clinical data extracted. Patients were included if they had been receiving lanadelumab for at least 6 months. Patients with other causes of angioedema were excluded. Results 12 patients meeting enrollment criteria were identified. Compared to pre-lanadelumab, patients had mean reductions of 72% and 62% in attack rate and treated attack rate respectively. 3 patients reported complete remission from attacks after starting lanadelumab. Most patients had significant improvements in HAE impact on social outings. Conclusion Our case series findings support the 2019 International/Canadian HAE guideline that lanadelumab is an effective therapy for long term prophylaxis. In our patient population, initiation of lanadelumab improved disease control, minimized the burden of treatment and improved HAE impact on social outings.

Anesthetic Management of Apert Syndrome: A Case Report

Apert syndrome is a rare autosomal dominant disease associated with abnormalities of skull, face and limbs. These patients present for different types of surgeries. To the anesthesiologists,they pose special challenge during airway management, manifesting as difficulty in bag-mask ventilation and increased incidence of airway obstruction. Here, we report a case of a child with Apert syndrome undergoing syndactyly release under general anesthesia, in whom severe bronchospasm and a failed bag-mask ventilation occurred during the emergence of anesthesia requiring re-insertion of laryngeal mask airway.

Congenital Microcoria: Clinical Features and Molecular Genetics

Iris integrity is required to regulate both the amount of light reaching the retina and intraocular pressure (IOP), with elevated IOP being a major risk factor for glaucoma. Congenital microcoria (MCOR) is an extremely rare, autosomal dominant disease affecting iris development and hindering both of these functions. It is characterized by absent or underdeveloped dilator muscle fibers and immaturity of the iridocorneal angle—where the aqueous humor is drained—which play a central role in IOP regulation. The dilator muscle anomaly is manifested in pinhole pupils (<2 mm) and thin transilluminable irises, causing both hemeralopia and photoaversion. Axial myopia and juvenile open-angle glaucoma are very frequent (80% and 30% of all cases, respectively). It has been suggested that the immaturity of the chamber angle contributes to glaucoma, and myopia has been ascribed to photoaversion and elevated IOP. Though possible, these mechanisms are insufficient. The disease has been tied to chromosome 13q32.1 structural variations. In addition to compromising iris development, modification of the 13q32.1 architecture could alter signaling pathways for axial ocular length and IOP regulation. Here, we summarize the clinical, histological, and molecular features of this disease, and we discuss the possible etiology of associated anomalies.

Functional Studies of Novel FOXL2 Variants in Chinese Families With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome

The blepharophimosis–ptosis–epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease mainly caused by FOXL2 variants. This genetic disorder is usually characterized by eyelid malformation and ovarian dysfunction. However, no reliable genotype/phenotype correlations have been established considering the ovarian phenotype. Here, we detected 15 FOXL2 variants including nine novel ones from 7 families and 8 sporadic cases, which expanded the spectrum of FOXL2 variants and identified a potential clinical cause. Functional studies, with respect to the effect of FOXL2 on the StAR promoter, showed that non-sense variants that lead to protein truncation before the polyalanine tract and missense variants [c.307C &gt; T; p.(Arg103Cys), c.311A &gt; C; p.(His104Pro), c.320G &gt; A; p.(Ser107Asn), and c.335T &gt; A; p.(Phe112Tyr)] within the central portion of the FOXL2 forkhead domain significantly affect its suppressor activity. Such changes may explain the mechanism underlying a more severe phenotype, more likely to result in BPES type I. Furthermore, the missenses variants c.307C &gt; T; p.(Arg103Cys), c.311A &gt; C; p.(His104Pro), and c.320G &gt; A; p.(Ser107Asn) were not able to transactivate OSR2, which is consistent with the eyelid malformation in these patients. The results from our cohort have expanded the spectrum of FOXL2 variants and have provided insights into genotype/phenotype correlations.

Who were those MEN hiding behind the Ulcers?: A Case Report

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disease caused by a mutation in the MEN1 gene. We present a 65-year-old man with MEN1 who has primary hyperparathyroidism, microprolactinoma, meningioma and gastrinoma. He had undergone parathyroidectomy followed by tumour excision of meningioma. The duodenal gastrinoma lesion was inoperable as it was close to the superior mesenteric artery with high surgery risk. Medical therapy with octreotide LAR had been initiated and showed good biochemical response as well as disease progression control. Chemoembolization was proposed if the duodenum lesion reduces in size on maintenance treatment with octreotide LAR. This case highlights the challenges in managing this rare condition and octreotide LAR has shown to be effective in controlling the disease progression in MEN1 with inoperable gastrinoma.

A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation

Background Mutations in TGM6 gene, encoding for transglutaminase 6 (TG6), have been implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease marked by cerebellar degeneration and characterized by postural instability, incoordination of gait, features of cerebellar dysfunction and pyramidal signs. Case presentation Here we report the case of an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech and ocular dysmetria and pyramidal tract signs. Whole exome sequencing revealed the rare heterozygous c.1024C > T (p.R342W) variant of TGM6, located at a highly evolutionary conserved position and predicted as pathogenic by in silico tools. Expression of TG6-R342W mutant in HEK293T cells led to a significant reduction of transamidase activity compared to wild-type TG6. Conclusion This finding extends SCA35 genetic landscape, highlighting the importance of TGM6 screening in undiagnosed late-onset and slowly progressive cerebellar ataxias.

Clinical presentation of hereditary angioedema

Hereditary angioedema (HAE) is a rare, autosomal dominant disease caused by a deficiency in the C1-inhibitor protein. It is characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous or submucosal edema that typically involves the extremities or the gastrointestinal tract. However, the genitourinary tract, face, oropharynx, and/or larynx may be affected as well. Symptoms often begin in childhood, worsen at puberty, and persist throughout life, with unpredictable severity. Patients who are untreated may have frequent attacks, with intervals that can range from every few days to rare episodes. Minor trauma and stress are frequent precipitants of swelling episodes, but many attacks occur without clear triggers. HAE attacks may be preceded by a prodrome and/or be accompanied by erythema marginatum. The swelling typically worsens over the first 24 hours, before gradually subsiding over the subsequent 48 to 72 hours. Although oropharyngeal swelling is less frequent, more than half of patients have had at least one episode of laryngeal angioedema during their lifetime. Attacks may start in one location and spread to another before resolving. HAE attacks that involve the abdomen or oropharynx have been associated with significant morbidity and mortality. Abdominal attacks can cause severe abdominal pain, nausea, and vomiting. Bowel sounds are often diminished or silent, and guarding and rebound tenderness may be present on physical examination. These findings may lead to unnecessary abdominal imaging and procedures. Fluid shifts into the interstitial space or peritoneal cavity can cause clinically significant hypotension. Laryngeal edema poses the greatest risk for patients with HAE. Although prompt diagnosis and treatment improves outcomes, the variable presentation of HAE can make it difficult to diagnose.

Angiogenesis, hereditary hemorrhagic telangiectasia and COVID-19

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominant disease characterized by pathologic angiogenesis that provokes vascular overgrowth. The evidence about the influence of Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in patients with rare diseases is scarce. We aimed to know the prevalence of coronavirus disease 2019 (COVID-19) in HHT patients. The HHT pathogenic angiogenesis and endothelial injury in COVID-19 are discussed using data from RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry. RiHHTa is an open, multicenter, prospective, observational registry including adult patients with HHT. A 27-item survey that captured clinical data of admitted HHT patients for COVID-19 was distributed to all RiHHTa investigators from June 8th to June 24th 2020. Only one out of 1177 HHT patients was admitted for COVID-19 pneumonia. She is a 74 years-old woman with a pathogenic variant in ACVRL1 gene. Her clinical course did not involve mechanical ventilation or worsening epistaxis, and she was successfully discharged after two weeks. The endothelial damage and the consequent angiogenic process in COVID-19 patients deserve further investigation.

Difficulties in clinical diagnosis the atypical form of Andersen-Tawil syndrome

Синдром Андерсена-Тавила - редкое аутосомно-доминантное заболевание, при котором развиваются нарушение сердечного ритма, периодический паралич, лицевые и скелетные дизморфии. Вариабельность клинических проявлений усложняет постановку верного диагноза. В статье описывается клинический случай и анализируются особенности течения заболевания у пациента, правильный диагноз которому поставлен благодаря результатам секвенирования. Andersen-Tawil syndrome is a rare autosomal dominant disease characterized by periodic paralysis, cardiac dysrhythmias, distinct facial and skeletal characteristics, that may be variably present in the affected members. In the article there is a clinical case with atypical presentations. The correct diagnosis has been done due to results of DNA sequencing.