Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations

Cleft lip with or without cleft palate (CLP and CL, respectively) and isolated cleft palate (CP) represent one of the most common human birth defects, with a prevalence of approximately 1 in 300-2500 depending on the population. Formation of non-syndromic CL/CLP and CP arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP4 gene (encoding bone morphogenetic protein 4) and non-syndromic CL/CLP and CP in order to clarify the role of this gene in the aetiology of the malformation in Latvian and Lithuanian populations. We genotyped three markers of the BMP4 gene (rs17563, rs2071047 and rs1957860) in order to perform single marker and haplotype association analyses for Latvian and Lithuanian non-syndromic CL/CLP and CP patients and controls. Transmission disequilibrium test was also conducted for Latvian and Lithuanian proband-parent trios. The case-control analysis revealed that SNP rs2071047 allele A was associated with a decreased risk of CL/CLP in the Latvian population, which was confirmed by the haplotype analysis. A modest association was detected between SNP rs1957860 and CP in the Lithuanian population, where allele C was associated with a decreased risk of this cleft phenotype, corroborating haplotype analysis data. Our findings support a role of the BMP4 gene in the aetiology of non-syndromic CL/CLP and CP in the studied populations.publishersversionPeer reviewe

Genotype and phenotype data analysis and visualization

In this paper, we present a comparative analysis of hierarchical clustering and multidimensional scaling methods for genotype and phenotype data analysis. Fisher's exact test was applied to determinate dependencies between congenital anomalies. In order to determine the relationship between the dependences of congenital anomalies, deformations, these systems’ micro anomalies and congenital anomalies associated with orofacial clefs, the Spearman and Kendall correlation coefficients were applied. It has been detected which methods are better for genetic data visualization

Juvenile Huntington’s disease: two case reports and a review of the literature

Background Huntington’s disease is a rare, autosomal dominant neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Usually, the disease symptoms first appear around the age of 40, but in 5–10% of cases, they manifest before the age of 21. This is then referred to as juvenile Huntington’s disease. According to the small number of cases reported in the literature, the course of juvenile Huntington’s disease significantly differs from adult onset and shows significant interpatient variability, making every case unique. Case presentation Our study aims to highlight the complexity and diversity of rare juvenile Huntington’s disease. We report cases of two Caucasian patients with chronic tics referred to the Huntington’s Disease Competence Center of Vilnius University Hospital Santaros Klinikos with suspicion of juvenile Huntington’s disease due to the appearance of chronic motor tics, and behavior problems. The diagnosis of juvenile Huntington’s disease was confirmed on both clinical and genetic grounds. In both cases described, the patients developed symptoms in all three main groups: motor, cognitive, and psychiatric. However, the first patient was experiencing more severe psychiatric symptoms; in the second case, motor symptoms (rigidity, tremor) were more prominent. In both cases, apathy was one of the first symptoms and affected patients’ motivation to participate in treatment actively. These two case descriptions serve as an important message for clinicians seeing patients with chronic tics and gradually worsening mood and behavior, indicating the need to investigate them for rare genetic disorders. Conclusions Description of these two clinical cases of juvenile Huntington’s disease provides insight into how differently it manifests and progresses in young patients and the difficulties the patients and their families face. There were different but painful ways for families to accept the diagnosis. Because the disease inevitably affects the patient’s closest ones, it is crucial to also provide adequate psychological and social support to all the family members. Establishment of multidisciplinary specialist centers for Huntington’s disease, as demonstrated by our experience, not only allows timely diagnosis and treatment plans but also ensures thorough disease management and care for patients and systematic support for their families

Genotype and phenotype data analysis and visualization

In this paper, we present a comparative analysis of hierarchical clustering and multidimensional scaling methods for genotype and phenotype data analysis. Fisher's exact test was applied to determinate dependencies between congenital anomalies. In order to determine the relationship between the dependences of congenital anomalies, deformations, these systems’ micro anomalies and congenital anomalies associated with orofacial clefs, the Spearman and Kendall correlation coefficients were applied. It has been detected which methods are better for genetic data visualization

Consensus recommendations on chewing, swallowing and gastrointestinal problems in Phelan-McDermid syndrome

Gastrointestinal (GI) problems are common in Phelan-McDermid syndrome (PMS). Chewing and swallowing difficulties, dental problems, reflux disease, cyclic vomiting, constipation, incontinence, diarrhoea, and nutritional deficiencies have been most frequently reported. Therefore, this review summarises current findings on GI problems and addresses the fundamental questions, which were based on parental surveys, of how frequent GI problems occur in PMS, what GI problems occur, what consequences (e.g., nutritional deficiencies) GI problems cause for individuals with PMS, and how GI problems can be treated in individuals with PMS. Our findings show that gastrointestinal problems have a detrimental effect on the health of people with PMS and are a significant burden for their families. Therefore, we advise evaluation for these problems and formulate care recommendations

Su lūpos ir/ar gomurio nesuaugimu susijusios anomalijos Lietuvoje

A routine screening for other associated malformations, especially skeletal, central nervous system and cardiac defects, is required

Significant Association Between Huntingtin Gene Mutation and Prevalence of Hopelessness, Depression and Anxiety Symptoms

International audienceBackground: In Huntington’s disease psychiatric symptoms may manifest prior to motor dysfunction. Such symptoms negatively impact people’s quality of life and can worsen the course of the primary disease. The aim of the present study was to assess and compare depression, anxiety and hopelessness rates in individuals with and without an abnormal expansion of CAG repeats in the huntingtin (HTT) gene and healthy controls.Materials and methods: Study involved 31 individuals referred for genetic testing for Huntington’s disease and a control group of 41. Depressive and anxiety symptoms were assessed using Beck Hopelessness Scale (BHS) and Hospital Anxiety and Depression Scale (HADS). Results between groups were compared using the Mann–Whitney U test. Two-sided Bonferroni corrected p-value was set at ≤0.017.Results: Individuals with HTT gene mutation (“gene mutation positive”, GMP) (N=20) scored higher on the HADS depression subscale (5.90 ± 4.52 vs 1.36 ± 1.91; p ≤ 0.017) than those without HTT gene mutation (“gene mutation negative”, GMN) (N=11). GMP and control groups scored higher than the GMN group on the BHS (5.65 ± 3.91 vs 2.09 ± 1.64 and 5.27 ± 4.11 vs 2.09 ± 1.64, respectively; p ≤ 0.017). No differences in anxiety levels were found.Conclusions: Depressive symptoms and hopelessness were more prevalent in individuals with HTT gene mutation than in individuals who were tested but had no said mutation. Such results emphasise the importance of timely diagnosis and treatment of psychiatric comorbidities in individuals affected by Huntington’s disease

A sporadic case of COL1A1 osteogenesis imperfecta: from prenatal diagnosis to outcomes in infancy—case report and literature review /

Osteogenesis imperfecta (OI), also known as brittle bone disease, belongs to a rare heterogeneous group of inherited connective tissue disorders. In experienced prenatal centers, severe cases of OI can be suspected before birth from the first trimester prenatal ultrasound screening. In this article, we describe a case report of OI suspected at the 26th week of gestation and the patient’s outcomes in infancy one year after birth, as well as compare our case to other prenatally or soon-after-birth suspected and/or diagnosed OI clinical case reports in the literature. This case was managed by a multidisciplinary team. In this clinical case, OI was first suspected when prenatal ultrasound revealed asymmetric intrauterine growth restriction and skeletal dysplasia features. The diagnosis was confirmed after birth using COL1A1 gene variant detection via exome sequencing; the COL1A1 gene variant causes OI types I–IV. The familial history was negative for both pregnancy-related risk factors and genetic diseases. At one year old, the patient’s condition remains severe with bisphosphonate therapy

Heterogeneity of Oral Clefts in Relation to Associated Congenital Anomalies

Background and Objective. The first step in the search for the genetic basis of oral clefts should be the well-accepted classification and clinical data protocols, which are important in distinguishing separate phenotypic groups. The aim of this study was to compare the frequency of congenital malformations associated with oral clefts between the different groups of oral clefts. Material and Methods. The study population comprised 238 patients with oral clefts and one or more major congenital anomalies. All cases of oral clefts were subdivided into 2 groups: patients with the recognized conditions (n=97, 40.8%) and patients with the multiple congenital anomalies of unknown origin (n=141, 59.2%). The frequency of associated congenital anomalies was compared between the cleft palate (CP) and cleft lip and/or palate (CL/P) groups as well as between the cleft lip only (CL) and cleft lip with cleft palate (CLP) subgroups. Results. A total of 420 anomalies associated with oral clefts were diagnosed in 141 patients with multiple congenital anomalies (2.98 anomalies per proband) with the highest incidence being in the CP group (3.5 anomalies per proband). Comparison of the CP and CL/P groups showed that some of associated congenital anomalies such as atresia and stenosis of the small intestine and micrognathia occurred significantly more often in the CP than CL/P group (2.1% vs. 0% and 3.5% vs. 1.1%; P<0.05). Meanwhile, comparison of the CL and CLP subgroups revealed accessory auricle, other specified anomalies of the ear, congenital anomalies of the circulatory system, and certain congenital musculoskeletal deformities of the spine to be more common in the CL than CLP group (5.1% and 0.5%, 11.9% and 5.1%, 3.4% and 0%, 3.4% and 0%, respectively; P<0.05). Conclusions. The highest incidence of associated congenital anomalies was in the CP group followed by the CL, CL/P, and CLP groups. Generally, the anomalies of the musculoskeletal system, cardiovascular system, and face including eye, ear, and neck were most common. The careful analysis of associated anomalies and cases of oral cleft subgroups with multiple congenital anomalies is helpful in identifying the etiologic entities and underscores the need for thorough evaluation and competent distinction of various types of oral clefts