Except for terminal deletions that lead to Jacobsen syndrome, interstitial deletions involving the long arm of chromosome 11 are not frequently reported. A clinically distinct phenotype is usually ...observed in these cases, and no clear genotype-phenotype correlation is proposed.
Here we present a case study of a 5-year-old girl with de novo submicroscopic deletion of chromosome 11q22.3 with mild mental retardation and facial dysmorphism. A standard cytogenetic analysis did not reveal any structural aberrations. In contrary, array-CGH analysis indicated a small deletion of 11q22.3.
To our knowledge, this is the smallest 11q22.3 deletion reported in literature, containing nine RefSeq genes. Although none of the deleted genes are obvious candidates for the features observed in our patient, genes CUL5 and SLN could play a key role in the features described.
To determine whether four potential genetic factors (polymorphisms in genes for alpha-adducin, beta-adducin, the G-protein beta-3 subunit and nitric oxide synthase) are important for the development ...of essential hypertension (EH) in Slovenian children and young adults with EH.
Both a nuclear families approach and case-control study have been performed. Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families (an affected child, both parents) and in 200 control patients.
Using the transmission disequilibrium test, no statistically significant differences were found between the frequencies of transmitted and non-transmitted alleles in nuclear families for all four investigated polymorphisms. In addition, the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients. The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations.
We found no association between the investigated gene variants and EH, so we conclude that they do not confer a significantly increased risk of the development of EH in the Slovenian population of hypertensive children.
During the past several years, 24-hour (24-h) ambulatory blood pressure monitoring (ABPM) has become a useful tool for the diagnosis and management of children and adolescents with elevated blood ...pressure (BP). Some reports have also provided blood pressure nomograms for particular devices. However, there are very few reports of the use of this method in very young children. In our study we investigated the applicability of ABPM in 97 healthy infants and toddlers, aged from 2 to 30 months. A satisfactory ABPM profile was obtained in 86.6% of the children, with an average of 75.0% satisfactory BP recordings. The mean +/- SD systolic and diastolic BP of healthy infants and toddlers was 99+/-12/62+/-12 mmHg during the daytime and 95+/-11/57+/-10 mmHg during the night, with no gender difference being observed. The 24-h mean +/- SD systolic and diastolic BP, which may be a more appropriate measure of BP in this particular age group, was found to be 97+/-12/59+/-11 mmHg. We also confirmed the increase in systolic and diastolic BP with increased height (length). There was only a slight nocturnal decrease in BP. We conclude that this method is applicable for the assessment of blood pressure in very young children.
The metabolic syndrome (MS) in adults is defined as a concurrence of obesity, disturbed glucose and insulin metabolism, hypertension and dyslipidemia, and is associated with increased morbidity and ...mortality from cardiovascular diseases and type 2 diabetes. Studies now indicate that many of its components are also present in children and adolescents. Moreover, the clustering of these risk factors has been documented in some children, who are at increased cardiovascular risk in adulthood. The MS is highly prevalent among overweight children and adolescents. Identifying these children is important for early prevention and treatment of different components of the syndrome. The first-line treatment comprises lifestyle modification consisting of diet and exercise. The most effective tool for prevention of the MS is to stop the development of childhood obesity. The first attempt at consensus-based pediatric diagnostic criteria was published in 2007 by the International Diabetes Federation. Nevertheless, national prevalence data, based on uniform pediatric definition, protocols for prevention, early recognition and effective treatment of pediatric MS are still needed.The aim of this article is to provide a short overview of the diagnosis and treatment options of childhood MS, as well as to present the relationships between MS and its individual components.
Hypertension during childhood is not rare, with an estimated prevalence of between 1% and 2%, although it is often an underrecognized clinical entity. Elevated blood pressure may be a sign of ...underlying disease or it may represent early onset of essential hypertension. In recent years the measurement of blood pressure has been emphasized as an important component of the routine pediatric physical examination that enables early detection of children with hypertension. In the evaluation of the child with documented blood pressure elevation, confirmation of truly and persistently elevated blood pressure is of the utmost importance. In addition, a thorough history and a full clinical examination are essential. These are followed by appropriate investigations, which are tailored to the age of the child and to the severity of the blood pressure elevation. Investigations should not only focus on a search for the underlying cause, but also on establishing effects on target organs, complications or additional diseases and on assessment of the total cardiovascular risk to the individual patient. An algorithm, which is a valuable diagnostic tool for the diagnosis and management of the child with hypertension, is presented. All children with confirmed hypertension need long-term follow-up, counseling and treatment. In those cases where an underlying cause of the hypertension is detected, the established diagnosis then determines the specific therapy and management.
Hepatocyte nuclear factor 1-beta (HNF1B) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although ...neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease.
This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype (HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate eGFR < 60 ml/min per 1.73 m2). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia.
Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio HR: 0.29, 95% confidence interval CI: 0.19–0.44, P < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POUh) DNA-binding and transactivation domains rather than the POU-specific domain (POUs) DNA-binding domain (HR: 0.15 95% CI: 0.06–0.37), P < 0.001 and HR: 0.25 (95% CI: 0.11–0.57), P = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia.
Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POUs DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling.
Display omitted
The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are ...to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes.
Purpose
The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics ...between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease.
Methods
This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods.
Results
This study enrolled 48 patients with a median age of 32.3 years (range, 18–46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis—83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (
p
-0.033 and 0.03, respectively).
Conclusion
Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.
PDF
