Chest wall deformities and their possible associations with different genetic syndromes.

OBJECTIVE: Our primary objective was to identify discrete and syndromic cases of Pectus excavatum (PE) and Pectus carinatum (PC). We also intended to highlight the significance of further genetic exploration in clinically suspected syndromic cases of PC and PE. Pectus excavatum (PE) and Pectus carinatum (PC) are the most common morphological chest wall deformities. Although various hypotheses have been put forth, the pathogenesis of both entities is largely unknown. Clinicians often refer such cases for further genetic evaluation to exclude an associated underlying connective tissue disorder or a syndrome. Additionally, a detailed anamnesis with focused family history and thorough dysmorphological physical examination was done. PE and PC are considered isolated abnormalities if there is the absence of features of other syndromes, eliminating the need for further genetic evaluations. It is believed that the pattern of inheritance of these non-syndromic isolated PE and PC cases with positive family history could be multifactorial in nature. The recurrence risk of such isolated cases is thought to be low. Further diagnostic studies are indicated as PE and PC could be a part of a syndrome. Among the many syndromes, the most common monogenic syndromes associated with PE and PC are Marfan's and Noonan's. PATIENTS AND METHODS: After obtaining the consent, we compiled a database of the patients who presented with chest wall deformities during the period 2017-2019. We selected 70 cases with PC and PE deformities to identify the discrete and syndromic PC and PE cases. During the study, we perused the cytogenetic and/or molecular analyses, that had been conducted to confirm the clinically suspected syndromic cases. We also scrutinized for the presence of PC and PE cases that are associated with the rare syndrome (s). RESULTS: Various genetic abnormalities were identified in 28 (40%) of the 70 cases that had been diagnosed with chest wall abnormalities. Along with PE and PC, other thoracic wall abnormalities were also identified, such as the broad chest, bell-shaped thorax, and elongated or enlarged thorax. One case of a rare genetic disorder of Morquio syndrome associated with PC was also identified. Novel (previously unpublished) genomic variants are reported here. CONCLUSIONS: It is important to delve deeper when encountering cases of PE and PC by conducting a further genetic exploration of such cases to identify syndromic associations that cause other structural and functional disorders, diagnosis of which might be missed during the early developmental period. Early identification of such disorders may help us correcting the defects, slowing the progression of disease processes, and preparing better to deal with the potential outcome.

Beta-blockers for the treatment of arrhythmias: Bisoprolol - a systematic review.

OBJECTIVES: Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical structure, pharmacokinetic and pharmacodynamic properties (absorption, bioavailability, metabolism, hydrophilic or lipophilic character, selective or non-selective nature, the presence or absence of intrinsic sympathomimetic activity), which may confer different antiarrhythmic properties to different beta-blockers. The aim of this study was to analyze the current existing evidence for bisoprolol for the treatment of both supraventricular and ventricular arrhythmias. MATERIAL AND METHODS: Using the keywords "bisoprolol" and "arrhythmias" or "atrial fibrillation" or "ventricular tachycardia" or "premature ventricular complexes" or "ventricular fibrillation", the Medline database was searched for articles in English or French until April 2020 assessing the role of bisoprolol in the treatment of arrhythmias. Data was then analyzed according to the type of arrhythmia treated and the quality of evidence using the GRADE approach. RESULTS: A total of 325 studies were identified, of which 28 were considered relevant to the current topic. Among these studies, 19 assessed the role of bisoprolol for the treatment of supraventricular arrhythmias, 8 its role in treating ventricular arrhythmias and 1 its role in supraventricular and ventricular arrhythmias. The quality of evidence varied from low (7 studies) to high (5 studies). CONCLUSION: Current evidence exists supporting the use of bisoprolol for the treatment of supraventricular arrhythmias, especially for rate control during atrial fibrillation. Evidence also exists for its efficacy in the treatment of ventricular arrhythmias, both in primary and in secondary prevention.

Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.

BACKGROUND AND PURPOSE: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. METHODS: Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6-2 mutations in a multicentre setting is described. Then, all reported NKX6-2 mutations and those identified in this study were combined and an in-depth analysis of NKX6-2-related disease spectrum was provided. RESULTS: Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6-2 were identified, evidencing a high NKX6-2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6-2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. CONCLUSIONS: NKX6-2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6-2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.

Antley-Bixler syndrome: surgical management of ambiguous genitalia - a case report.

OBJECTIVE: To report a case of type 2 Antley-Bixler syndrome (ABS). SUBJECT AND METHODS: A 3-year-old boy who had been raised male, with facial dimorphism and malformations of both elbows and forearms, was referred to our unit for ambiguous genitalia. Genetic testing confirmed the diagnosis of ABS. A surgical intervention was performed to correct the ambiguous genitalia through a combined perineal and transabdominal approach. RESULTS: The postoperative course was uneventful and the patient was released from the hospital 10 days after the surgery. CONCLUSION: Repair of the ambiguous genitalia in this patient was possible, but definitive inferences on the benefit of this intervention cannot be made without long-term follow-up.

Retinoic acid receptor ß2 (RARß2): nonivasive biomarker for distinguishing malignant versus benign prostate lesions from bodily fluids.

UNLABELLED: Alterations in the methylation patterns of promoter CpG islands have been associated with the transcriptional inhibition of genes in many human cancers, including prostate cancer (PCa). OBJECTIVES: The aim of our study was to evaluate the diagnostic value of aberrant promoter hypermethylation of retinoic acid receptor ß2 (RARß2) gene in serum DNA samples from patients with the diagnosis of PCa and benign prostatic hyperplasia (BPH), as a new epigenetic biomarker in distinguishing between malignant and non-malignant lesions. MATERIALS AND METHODS: Aberrant promoter hypermethylation was investigated in genomic DNA isolated from the serum of 91 patients diagnosed with of PCa and 94 with BPH (control subjects). In order to evaluate the methylation status of the RARß2 gene we used the quantitative methylation-specific PCR (QMSP) method. RESULTS: Promoter hypermethylation of RARß2 gene was detected in serum samples from 89 of 91 (92.86%) patients with PCa, and in 10 of the 94 (10.7%) patients with BPH. CONCLUSIONS: RARß2 represents a promising molecular biomarker which may be used in discriminating between malignant and benign prostatic diseases by noninvasive methods.

[Genetic studies in retinoblastoma]. / Cercetari genetice în retinoblastom.

For a fifteen year period it has been hospitalized in Ophthalmologic Clinic from Craiova nineteen cases with retinoblastoma, seventeenth of them have been sporadic forms and two hereditary forms. It was found chromosomal changes at the two hereditary forms, consisting by a deletion of the long arm of chromosome 13.