Clinical and genetic study of two patients with Zimmermann–Laband syndrome and literature review

Zimmermann–Laband syndrome (ZLS) is a rare MCA/MR condition mainly characterized by gingival hypertrophy, hypo/aplastic nails and distal phalanges, hypertrichosis and intellectual disability. The molecular basis of ZLS is unknown. Most patients are sporadic, although familial aggregation is also observed with different inheritance patterns. We report on two unrelated children with full-blown characteristics of ZLS. Remarkable variability in expression included severity of neurocognitive involvement and extent of appendicular and facial features. In both, comparative genome hybridization array at a ∼75 Mb resolution resulted negative, while aminoacid metabolic screening revealed high plasma levels of hypoxanthine and xanthine in one. Literature review identified 50 previously published patients (27 females, 23 males), including 14 familial, clustered in four pedigrees, and 37 sporadic. Tabulation of clinical features confirmed the core phenotype and identified developmental delay as the unique major clinical problem (occurring in 40% of the cases) with a moderately high risk of epilepsy (13%). Segregation analysis in the 20 sporadic patients with available data on healthy sibs and a single pedigree with affected sibs was significantly in contrast with an autosomal recessive mutation. An autosomal dominant mutation with high mutation rate and rare instances of germinal mosaicism seems the most likely inheritance pattern. This work may represent a starting point for future molecular studies aimed at identifying the molecular basis of ZLS.     

Clinical manifestation and cytogenetic analysis of 607 patients with Turner syndrome北大核心CSCD

Objective To explore the correlation between cytogenetic findings and clinical manifestations of Turnersyndrome. Methods 607 cases of cytogenetically diagnosed Turner syndrome, including those with a majormanifestation of Turner syndrome, were analyzed with conventional G-banding. Correlation between the karyotypes and clinical features were analyzed. Results Among the 607 cases, there were 154 cases with monosomy X (25.37%). Mosaicism monosomy X was found in 240 patients (39.54%), which included 194 (80.83%) with a lowproportion of 45,X (3 ≤ the number of 45, X ≤5, while the normal cells ≥ 30). Structural X chromosomeabnormalities were found in 173 patients (28.50%). A supernumerary marker chromosome was found in 40 cases (6.59%). Most patients with typical manifestations of Turner syndrome were under 11 years of age and whosekaryotypes were mainly 45,X. The karyotype of patients between 11 and 18 years old was mainly 45, X, 46, X,i(X) (qlO) and mos45,X/46, X, i (X) (qlO), which all had primary amenorrhea in addition to the typical clinical manifestations. The karyotype of patients over 18 years of age were mainly mosaicism with a low proportion of45,X, whom all had primary infertility. 53 patients had a history of pregnancy, which included 48 withnon-structural abnormalities of X chromosome and 5 with abnormal structure of X chromosome. ConclusionGenerally, the higher proportion of cells with an abnormal karyotype, the more severe were the clinicalsymptoms and the earlier clinical recognition. Karyotyping analysis can provide guidance for the earlydiagnosis of Turner syndrome, especially those with a low proportion of 45,X.     

Efficacy and safety of choline alphoscerate (cereton) in patients with parkinson’s disease with cognitive impairments

An open 10-day study in which the therapeutic actions of Cereton were compared with those of piracetam was performed. Cereton was used in 40 patients (experimental group) at a dose of 1000 mg, while piracetam was used in 20 patients at a dose of 2000 mg; both agents were given as intravenous infusions in 200 ml of physiological saline on the background of antiparkinsonism agents. Patients’ status was evaluated using a complex of psychometric scales and neuropsychological tests, along with tools to assess the severity of the main symptoms of parkinsonism, side effects, and quality of life. Use of Cereton produced marked and moderate improvements in the state of cognitive functions more frequently than piracetam (40% and 25%, respectively), while the incidence of deterioration was lower (5% and 15%, p < 0.05). Cereton was very well tolerated by the patients: brief and short-term side effects were seen in only six patients (15%).     

Clinical characteristics and peripheral T cell subsets in Parkinson’s disease patients with constipation

Constipation is frequently reported in Parkinson’s disease (PD). We evaluated the characteristics of patients with PD and constipation and explored the role of T cell subsets in PD-associated constipation. One hundred and two patients with PD treated at the First Affiliated Hospital of Bengbu Medical College were enrolled in this study between January 2012 and October 2013. All patients completed KESS questionnaires and constipation was rated. The proportions of peripheral blood Thl7 and Treg cells were assessed by flow cytometry in 45 patients. Colonoscopies were performed in six patients. Thirty-one patients with PD reported slow-transit constipation (STC), 15 rectal evacuation disorder (RED) and 33 mixed constipation (Mixed). STC most frequently occurred before onset of PD motor symptoms, while Mixed occurred before or after motor symptoms, and RED occurred most frequently after motor symptoms. CD4⁺ T cell infiltration in the colonic mucosa was observed in patients with PD and constipation. The frequency of Th17 and Treg cells in patients with PD and constipation was significantly higher than in those without constipation (P<0.001). Among patients with PD and constipation, the frequency of Th17 and Treg cells in STC was the highest. However, there was no difference in the ratio of Th17/Tregs between the patients with PD with and without constipation, or patients with PD and different types of constipations (P>0.05). Constipation reported before the onset of PD motor symptoms was most often STC or Mixed, and PD constipation may be associated with immune activation in the colonic mucosa.     

Clinical and Biochemical Heterogeneity of Parkinson’s Disease

Neuroscience and Behavioral Physiology - Objectives. To study the relationship between measures of oxidative stress and clinical changes in patients with neurodegenerative parkinsonism and identify...     

Predicting lymphoma development in patients with Sjögren’s syndrome

ABSTRACT

Introduction: The issue of predicting lymphoma in primary Sjögren’s syndrome (pSS) starts from its clinical and biologic essence, i.e., an autoimmune exocrinopathy with sicca syndrome, inflammation and lymphoproliferation of MALT (mucosa-associated lymphoid tissue) in exocrine glands.

Areas covered: The two major predictors to be firstly focused are persistent salivary gland (SG) swelling and cryoglobulinemic vasculitis with related features as purpura and low C4, or the sole serum cryoglobulinemia repeatedly detected. They are pathogenetically linked and reflect a heavier MALT involvement by histopathology, with the expansion of peculiar rheumatoid factor (RF)-positive clones/idiotypes. Other predictors include lymphadenopathy, splenomegaly, neutropenia, lymphopenia, serum beta2-microglobulin, monoclonal immunoglobulins, light chains, and RF. Composite indexes/scores may also predict lymphoma.

Expert opinion: Prediction at baseline needs amelioration, and must be repeated in the follow-up. Careful clinical characterization, with harmonization and stratification of large cohorts, is a relevant preliminary step. Validated and new biomarkers are needed in biologic fluids and tissues. SG echography with automatic scoring could represent a future imaging biomarker, still lacking. Scoring MALT involvement in pSS, as an additional tool to evaluate disease activity and possibly to predict lymphoma, is welcomed. All these efforts are now ongoing within the HarmonicSS project and in other research initiatives in pSS.     

Case of Lemierre’s syndrome presenting with thyroid abscess

Lemierres syndrome is an uncommon condition characterized by post-anginal septicemia due to anaerobes. Reported here is a case of Lemierres syndrome presenting with thyroid and liver abscesses. At presentation, the 70-year-old female patient complained of fever, jaundice and neck pain. Computed tomography (CT) and ultrasound confirmed the presence of a left-sided internal jugular vein thrombosis as well as abscesses in the left thyroid lobe and the right lobe of the liver with pleural effusion. The thyroid abscess was treated with a left lobectomy.     

Clinical, serologic, and genetic profiles of patients with associated Sjögren's syndrome and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) and Sj?gren's syndrome (SS) can coexist in patients. The aim of this study was to investigate the clinical, laboratory, and serologic features of the association of the two diseases. Data from 56 patients having both SS and SLE were analyzed, with special emphasis on their clinical, laboratory, and serologic features. Data from 50 patients with SLE and 50 patients with SS served as control subjects. The mean age in SS-SLE group was lower than in patients with SS but higher than patients with SLE. When SLE and SS were associated, presence of rheumatoid factor was less frequent, whereas anti-Ro/SS-A, anti-La/SS-B, antinuclear, anti-DNA, and antiphospholipid autoantibodies appeared more often. Antiphospholipid syndrome, anemia, leucopenia, and lymphopenia were more frequent in the associated disease than in patients with SS alone. In SS-SLE patients, pulmonary, renal, skin, central nervous system involvement, and serositis occurred more often than in patients with SS alone. Thyroiditis, autoantibodies to Ro/SS-A, La/SS-B and ds-DNA was more frequent in the SS-SLE group than in patients with SLE. Genetic background of the patients did not differ significantly. In conclusion, characteristic clinical, laboratory and serologic features distinguish between the association of SS and SLE and the primary forms of these two diseases.     

Maltoma of the thyroid and Sjögren’s syndrome in a woman with Hashimoto’s thyroiditis

We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren’s syndrome, and a history of Hashimoto’s thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with l-thyroxine for Hashimoto’s thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren’s syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto’s thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.     

Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients

Extramammary Paget’s disease (EMPD) is a rare cutaneous neoplasm. The aim of this study was to elaborate the clinical and pathological features of Chinese EMPD male patients. The study comprised 246 patients with EMPD at our institute from January 1993 to December 2012. Scrotum was the most common initial site. The average age of onset was 63.9 years but the mean delay in diagnosis was 3.6 years. EPMD spread exclusively to the inguinal lymph nodes and the right inguinal lymph nodes are more likely to suffered Paget cells infiltration. Accompanying malignancies were found in 20 patients. Pathological examination revealed 63 patients defined as invasive EMPD. Immunohistochemical detection showed various expression levels of EMA, CEA, CK7, HER2/neu, Ki67, P53, CK20 and S100 in tumor tissues, but negative expression of VIM, LCA and HMB45. HER2/neu protein exhibited a significant association with invasive EMPD. A novel histological type of EMPD with CK7-/S100+ was identified. Elevated serum PSA level was observed in only 16% patients. Invasive EMPD often had advanced age of onset. Metastatic EMPD showed significantly shorter in the delay in diagnosis and the greater length of skin lesion in contrast to others. This study demonstrates the clinical and pathological features of Chinese male EMPD patients, and may provide implications for the management of Chinese EMPD patients.     

Association of immunological features with clinical manifestations in primary Sjogren’s syndrome: a single-center cross-sectional study

Clinical and Experimental Medicine - The objectives of this study were to describe the clinical features and evaluate the utility of immunological features as predictors of organ involvement and...     

Clinical and immunological parameters of Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis.     

Molecular diagnosis of Fusobacterium necrophorum infection (Lemierre’s syndrome)

Presented here is the case of a 27-year-old male with atypical features of Lemierres syndrome in which a definitive diagnosis was achieved using molecular methods. While routine investigations, including bacterial cultures, were unhelpful, two real-time PCR assays demonstrated Fusobacterium necrophorum-specific DNA in aspirates from brain and renal abscesses. This is the first report demonstrating that a laboratory diagnosis can be made using molecular methods in suspected cases of Lemierres syndrome. Use of these methods can thus resolve diagnostic confusion, prevent unnecessary investigation, and direct specific antimicrobial treatment.     

Intrauterine phenotype features of fetuses with Williams–Beuren syndrome and literature review

Williams–Beuren syndrome (WBS) is a well-defined multisystem chromosomal disorder that is caused by a chromosome 7q11.23 region heterozygous deletion. We explored prenatal diagnosis of WBS by ultrasound as well as multiple genetic methods to characterize the structural variants of WBS prenatally. Expanded noninvasive prenatal testing (NIPT-plus) was elected as a regular prenatal advanced screen for risk assessments of fetal chromosomal aneuploidy and genome-wide microdeletion/microduplication syndromes at the first trimester. At the second and three trimester, seven prenatal cases of WBS were evaluated for the indication of the invasive testing, the ultrasound features, cytogenetic, single-nucleotide polymorphism array (SNP array), and fluorescent quantitative PCR (QF-PCR) results. The NIPT-plus results for seven fetuses were low risk. All cryptic aberrations were detected by the SNP array as karyotyping analyses were negative. Subsequently, QF-PCR further confirmed the seven deletions. Combining our cases with 10 prenatal cases from the literature, the most common sonographic features were intrauterine growth retardation (82.35%, 14/17) and congenital cardiovascular abnormalities (58.82%, 10/17). The manifestations of cardiovascular defects mainly involve supravalvar aortic stenosis (40%, 4/10), ventricular septal defect (30%, 3/10), aortic coarctation (20%, 2/10), and peripheral pulmonary artery stenosis (20%, 2/10). To the best of our knowledge, this is the first largest prenatal study of WBS cases with detailed molecular analysis. Aortic coarctation combined with persistent left superior vena cava and right aortic arch cardiovascular defects were first reported in prenatal WBS cases by our study.     

Ultrastructural findings of cutaneous nerves in patients with Hunter’s syndrome following hematopoietic stem cell transplant

Hematopoietic stem cell transplant (HSCT) has been performed on patients with Hunters syndrome. If applied, evaluation of recovery in various organs is needed for long-term follow-up. However, it remains unclear whether HSCT is effective against the neurological involvement in Hunters syndrome, and morphological evaluation of recovery is inconsistent. We observed the degree of cutaneous nerve involvement in patients with Hunters syndrome ultrastructurally before and after HSCT. Electron microscopic studies revealed that membrane-bound clear vacuoles were still observed in the cytoplasm of endoneurial fibroblasts and Schwann cells 2 months and 2 years, respectively, after HSCT. On the other hand, only a few vacuoles were present in dermal fibroblasts at 2 months after HSCT, and these disappeared within 2 years. These results suggest that the persistence of clear vacuoles in endoneurial fibroblasts and Schwann cells indicates a disturbed internal condition in the endoneurium 2 years after HSCT. Skin biopsies can be used in patients with Hunters syndrome to study peripheral nerves for long-term follow-up to evaluate morphological efficacy.