Japanese 17q12 Deletion Syndrome with Complex Clinical Manifestations.

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis - A cross sectional study.

OBJECTIVES: Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. METHODS: A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. RESULTS: 64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. CONCLUSION: In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. CLINICAL SIGNIFICANCE: Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

Chapter 4: Development Defects of Enamel and Dentine and Coronal Caries.

The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in the characteristics of enamel, dentine, and cementum. This chapter will focus on developmental defects of dental enamel (DDE) and dentine (DDD), which can be associated with considerable treatment burden on an individual, often related to the change in dental hard tissue characteristics in those at increased caries risk. DDE are prevalent and can be related to genetic conditions such as amelogenesis imperfecta and environmental challenges such as direct physical trauma to the developing tooth or systemic insults during the different phases of amelogenesis. Phenotypical variability can be great, making diagnosis difficult in many cases. There are two major enamel defects - the quantitative defect of hypoplasia and the qualitative defect of hypomineralization. DDDs are less prevalent than DDEs, with two major DDD types: dentinogenesis imperfecta and dentine dysplasia. The main features of the DDDs are enamel fracture exposing the dentine and subsequent wear, with enlarged pulp spaces in some variants. The appearance may be affected, with bulbous teeth and grey-blue to brown opalescent colouring. With respect to dental caries, developmental defects of the teeth, in themselves, do not cause caries risk; however, they can change the manifestation of the disease due to creating niches for biofilm accumulation and thereby increasing cleaning difficulty and changing the physical and chemical characteristics of dental hard tissues and how they react to cariogenic challenges.

Prevalence and influence of dental development anomalies in smile esthetics: a cross-sectional analysis

Aim: To determine the prevalence of dental development anomalies and type of influence on the smile of adolescent students. Method: This was a cross-sectional and analytical study carried out in two public (A1) and two private (A2) schools chosen by lot in the city of Parnaíba-Piauí. The sample calculation was based on the target population: number of people enrolled in public and private schools between 15 and 19 years, in the city of Parnaíba-PI, which totaled 6209 students in 2020, according to a survey carried out by the Brazilian Institute of Geography and Statistics ­ IBGE. A questionnaire on epidemiological data and aesthetic self-perception of the smile was applied to 160 adolescents between 15 and 19 years old, from August 2020 to July 2021. The clinical examination was carried out under natural light, to check for the presence of anomaly(s) in the dental development. Students who presented only one pathology would be called group 1 (G1), those who presented two would be called group 2 (G2) and those who presented 3 or more would be called group 3 (G3). On the other hand, adolescents in whom no anomaly was evidenced would participate in the control group (CG), both in A1 and A2. Results: It was observed that 37.5% of the sample had only a type of dental anomaly, corresponding to 60 individuals. The most prevalent were enamel hypoplasia, fusion, transposition, agenesis, ectopic eruption, microdent and dens-in-dent. It was possible to verify a higher prevalence in the maxilla, private schools (76.6%) and females (86.6%). In 45% of adolescents with dental anomalies, embarrassment was observed when smiling. Conclusion: The prevalence was relatively high, highlighting the enamel hypoplasia, influencing the smile esthetics of a reasonable number of adolescents, whether for acquaintances, strangers or even for photographs

The Association of Developmental Dental Defects and the Clinical Consequences in the Primary Dentition: A Systematic Review of Observational Studies.

Purpose: Assess whether children with developmental defects of enamel (DDE) in primary teeth have a higher risk of having dental caries or a higher prevalence of clinical consequences due to the disease than those without DDE. Methods: Search was performed in PubMed, Scopus, Web of Science™, Cochrane Library, LILACS, BBO, Embase databases and in gray literature. Three independent reviewers were involved in study selection, data extraction, and bias assessment. Risk of bias was evaluated by the Newcastle-Ottawa scale. DDE and its subtypes (demarcated opacities, hypoplasia, hypomineralized second primary molars (HSPM), and fluorosis) were regarded as exposure. Dental caries and clinical consequences of untreated caries were also assessed. In the meta-analyses, odds ratio (OR) was used in the random effects model for dichotomous outcomes. Quality of evidence was assessed using the Grading Recommendations Assessment, Development and Evaluation (GRADE). Results: The search yielded 5,750 studies, 39 of which were included in the systematic review and 20 in the meta-analysis. The risk of bias ranged from 4 to 9 points. Children with DDE were more prone to primary tooth caries (OR=2.79; 95% CI:1.29-6.03), and so were those with demarcated opacities (OR=1.75; 95% CI:1.09-2.78), hypoplasia (OR=2.84; 95% CI:1.73-4.67), and HSPM (OR=2.89; 95% CI:1.65-5.06). Fluorosis was not associated with caries (OR=1.39; 95% CI:0.97-1.98). Regarding tooth as a unit of analysis, DDE was highly associated with caries (OR=2.34; 95% CI:1.74-3.16). As for the clinical consequences of caries, only the qualitative analysis was conducted and there was no consensus in the studies. Conclusion: DDE is associated with higher primary tooth caries experience.

The Clinical Characteristics and Gene Mutations of Maturity-Onset Diabetes of the Young Type 5 in Sixty-One Patients.

Aims: Maturity-onset diabetes of the young type 5 (MODY5), a rare disease, is very easy to be misdiagnosed as type 2 diabetes. To get better understanding of the disease, we analyzed the clinical characteristics and gene mutations of MODY5. Methods: PubMed, Cochrane, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "MODY5" OR "HNF1B maturity-onset diabetes of the young" OR "maturity-onset diabetes of the young type 5" OR "renal cysts and diabetes syndrome". Clinical characteristics and gene mutations of MODY5 were analyzed. The demography, clinical characteristics, and blood indicators of patients were described utilizing simple summary statistics. Variables were analyzed by t-test, Wilcoxon signed rank test, and Fisher exact test. Spearman's correlation analysis was used for bi-variate analysis. All tests were two-sided, and a p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows (SPSS). Results: A total of 48 literatures were included in this study, including 61 eligible patients and 4 different mutations. Of the 39 patients with available body weight index, 15 (38.46%) were underweight, 21 (53.85%) were normal weight and 3 (7.69%) were overweight or obese. Of the 38 patients with available family history, 25 (65.79%) reported a family history of diabetes. Of the 34 patients with available age of diabetes diagnosis, the median age of diabetes diagnosis was 16.00 years old and 88.24% (30/34) of patients were under 25 years old when they were first diagnosed with diabetes. Renal cysts were presented in 72.41%, hypomagnesemia in 91.67%, and pancreatic dysplasia in 71.88% of the patients. Patients with hepatocyte nuclear factor 1B (HNF1B) deletion had lower serum magnesium, serum creatinine, and higher eGFR than patients with other gene mutations, and the difference was statistically significant. Conclusions: The young onset of diabetes with low or normal BMI, renal cysts, hypomagnesemia, and pancreatic dysplasia should be recommended to genetic testing in order to differentiate MODY5 from other types of diabetes earlier.

A case of familial recurrent 17q12 microdeletion syndrome presenting with severe diabetic ketoacidosis.

BACKGROUND: Heterozygous intragenic mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B) located on chromosome 17 and microdeletion of 17q12 region (17q12MD) leads to the complete loss of this gene, which causes renal cystic disease, diabetes mellitus (MODY5), hypomagnesemia, hyperuricemia, liver enzyme abnormalities, genital tract abnormalities and exocrine pancreatic insufficiency. In addition, patients with 17q12MD also have facial dysmorphism, neuro-developmental and neuropsychiatric disorders. CASE: A 16-year-old girl with obesity and mild facial dysmorphism was admitted to the hospital with symptoms of diabetes that started two days prior to her admission. She was diagnosed with severe diabetic ketoacidosis and treated accordingly. She had been followed up with the diagnoses of multicystic renal disease, hydronephrosis, hepatosteatosis, hypomagnesemia and hyperuricemia since the age of six. She had mild intellectual disability. Her menarche started two months ago. Cranial magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy and a partial empty sella. Her mother had diabetes, hypomagnesemia and mild intellectual disability and her maternal grandfather and uncle had diabetes. Her grandfather also had renal cystic disease. All of them are on oral antidiabetic medication. The genetic analysis of the patient and her mother revealed a loss of 1.6 megabases in chromosome 17q12. CONCLUSIONS: MODY5 should be kept in mind in patients with diabetes who present with extra pancreatic findings, especially with renal cystic disease, more over, a genetic analysis including the study of 17q12MD should be carried out in patients who present with additional neuropsychiatric findings. Ketoacidosis can be seen in patients with MODY5. Ketoacidosis and renal anomalies and dysfunction are factors that increase and affect the severity of each other in these patients.

Maternal-Child Health Indicators Associated with Developmental Defects of Enamel in Primary Dentition.

Purpose: To assess the prevalence and severity of developmental defects of enamel (DDE) in primary teeth and maternal-associated factors. Methods: This cross-sectional study included 336 two- to four-year-old children who attended the National Day of Children's Vaccination in São Paulo State, Brazil. The modified DDE index was used for diagnosis. Mothers completed sociodemographic and health questionnaires. Descriptive and Poisson regression analyses were performed. Results: The prevalence of DDE was 50.6 percent. The most frequent defects were demarcated opacities (45.0 percent), diffuse (36.0 percent) opacities, and hypoplasia (5.8 percent). White opacities were predominant (64.8 percent) in the teeth with defects, followed by cream (20.4 percent), yellow (5.2 percent), and brown (1.9 percent). Most defects involved less than one-third of the tooth surface (80.2 percent). The prevalence of DDE was associated with maternal-child factors such as alcohol consumption during pregnancy (prevalence ratio [PR] equals 1.27; 95 percent confidence interval [95% CI] equals 1.03 to 1.55), child hospitalization for infectious disease in the first year of life (PR equals 1.32; 95% CI equals 1.05 to 1.67), and breastfeeding for the first 12 months of life (PR equals 0.53; 95% CI equals 0.45 to 0.62). Conclusions: Developmental defects of enamel showed high prevalence and mild severity in the primary dentition. Alcohol consumption during pregnancy and child hospitalization for infectious diseases in the first year of life were associated with an increased prevalence of DDE. Moreover, children who breastfed for 12 months had a lower prevalence of DDE in primary teeth.

Establishment of PLAFMCi005-A induced pluripotent stem cells derived from PBMC from a patient with renal cysts and diabetes syndrome.

Renal cysts and diabetes syndrome (RCAD) is caused by gene mutations in hepatocyte nuclear factor 1-ß (HNF1B), but the underlying molecular mechanism is still unclear. This study established PLAFMCi005-A human induced pluripotent stem cells (iPSCs) by reprogramming peripheral blood mononuclear cells (PBMCs) from an RCAD patient. PLAFMCi005-A has differentiation potential and can be used to investigate the pathogenesis of RCAD caused by HNF1B gene mutations, thus promoting the development of related drugs.

Blood pressure in children with renal cysts and diabetes syndrome.

Cystic kidney diseases such as autosomal recessive or dominant polycystic kidney disease (ARPKD and ADPKD) are associated with high prevalence of arterial hypertension. On the contrary, studies on hypertension in children with renal cysts and diabetes (RCAD) syndrome caused by abnormalities in the HNF1B gene are rare. Therefore, the primary aim of our study was to investigate the prevalence of high blood pressure in children with RCAD syndrome due to HNF1B gene abnormalities and secondary to search for possible risk factors for development of high blood pressure. Data on all children with genetically proven RCAD syndrome from three pediatric nephrology tertiary centers were retrospectively reviewed (office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), creatinine clearance, renal ultrasound, echocardiography, albuminuria/proteinuria). High blood pressure was defined as BP ≥ 95th percentile of the current ESH 2016 guidelines and/or by the use of antihypertensive drugs. Thirty-two children with RCAD syndrome were investigated. Three children received ACE inhibitors for hypertension and/or proteinuria. High blood pressure was diagnosed using office BP in 22% of the children (n = 7). In the 7 performed ABPM, 1 child (14%) was diagnosed with hypertension and one child with white-coat hypertension. Creatinine clearance, proteinuria, albuminuria, body mass index, enlargement, or hypodysplasia of the kidneys and prevalence of HNF1B-gene deletion or mutation were not significantly different between hypertensive and normotensive children.Conclusion: High blood pressure is present in 22% of children with RCAD syndrome. What is Known: • Arterial hypertension is a common complication in children with polycystic kidney diseases. What is New: • High office blood pressure is present in 22% and ambulatory hypertension in 14% of children with renal cyst and diabetes (RCAD) syndrome.

Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model.

Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b ablation leads to more severe phenotypes. We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor site. Unlike heterozygous mice previously characterized, mice heterozygous for the splicing mutation exhibited decreased HNF1B protein levels and bilateral renal cysts from embryonic day 15, originated from glomeruli, early proximal tubules (PTs) and intermediate nephron segments, concurrently with delayed PT differentiation, hydronephrosis and rare genital tract anomalies. Consistently, mRNA sequencing showed that most downregulated genes in embryonic kidneys were primarily expressed in early PTs and the loop of Henle and involved in ion/drug transport, organic acid and lipid metabolic processes, while the expression of previously identified targets upon Hnf1b ablation, including cystic disease genes, was weakly or not affected. Postnatal analyses revealed renal abnormalities, ranging from glomerular cysts to hydronephrosis and, rarely, multicystic dysplasia. Urinary proteomics uncovered a particular profile predictive of progressive decline in kidney function and fibrosis, and displayed common features with a recently reported urine proteome in an RCAD pediatric cohort. Altogether, our results show that reduced HNF1B levels lead to developmental disease phenotypes associated with the deregulation of a subset of HNF1B targets. They further suggest that this model represents a unique clinical/pathological viable model of the RCAD disease.

Insights into the etiology and physiopathology of MODY5/HNF1B pancreatic phenotype with a mouse model of the human disease.

Maturity-onset diabetes of the young type 5 (MODY5) is due to heterozygous mutations or deletion of HNF1B. No mouse models are currently available to recapitulate the human MODY5 disease. Here, we investigate the pancreatic phenotype of a unique MODY5 mouse model generated by heterozygous insertion of a human HNF1B splicing mutation at the intron-2 splice donor site in the mouse genome. This Hnf1bsp2/+ model generated with targeted mutation of Hnf1b mimicking the c.544+1G>T (T) mutation identified in humans, results in alternative transcripts and a 38% decrease of native Hnf1b transcript levels. As a clinical feature of MODY5 patients, the hypomorphic mouse model Hnf1bsp2/+ displays glucose intolerance. Whereas Hnf1bsp2/+ isolated islets showed no altered insulin secretion, we found a 65% decrease in pancreatic insulin content associated with a 30% decrease in total large islet volume and a 20% decrease in total ß-cell volume. These defects were associated with a 30% decrease in expression of the pro-endocrine gene Neurog3 that we previously identified as a direct target of Hnf1b, showing a developmental etiology. As another clinical feature of MODY5 patients, the Hnf1bsp2/+ pancreases display exocrine dysfunction with hypoplasia. We observed chronic pancreatitis with loss of acinar cells, acinar-to-ductal metaplasia, and lipomatosis, with upregulation of signaling pathways and impaired acinar cell regeneration. This was associated with ductal cell deficiency characterized by shortened primary cilia. Importantly, the Hnf1bsp2/+ mouse model reproduces the pancreatic features of the human MODY5/HNF1B disease, providing a unique in vivo tool for molecular studies of the endocrine and exocrine defects and to advance basic and translational research. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Treatment of developmental defects of enamel.

Developmental defects of enamel are encountered daily in our dental practice. The management of enamel hypomineralized lesions may be challenging, especially as esthetic concern around the young population is increasing. Resin infiltration, a new technique firstly proposed to halt caries progression in the posterior segment, showed a strong positive esthetic effect in the treatment of developmental defects with different etiologies. Future in-vivo studies are needed to evaluate the longterm color stability, in order to provide a strong clinical recommendation.

Maxillary incisor enamel defects in individuals born with cleft lip/palate.

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p <0.001; OR = 7.15, CI: 4.674> 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p <0.001). Regardless of the cleft side, individuals with BCLP were 7.85 times more likely to have more than one third of the tooth surface affected, showing more frequently defects in the three thirds (OA: p <0.001) (IA: p = 0.03), as well as a higher frequency of more than one type of defect (OA: p = 0.000358) (IA: p = 0.008016), whereas in UCLP, defects were isolated and restricted to only one third, more frequently, the incisal third (OA: p = 0.009) (IA: p = 0.001), with greater frequency of milder defects, such as demarcated (p = 0.02) and diffuse (p = 0.008) opacities. A higher frequency of the T allele, less common, was observed in the group of CLP individuals who had all the affected teeth or at least two teeth with %SAD greater than 20% (p = 0.019843). Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.

New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-Of-Function Mutation.

Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist: A case report.

RATIONALE: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. PATIENT CONCERNS: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. DIAGNOSIS: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. INTERVENTIONS: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. OUTCOMES: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. LESSONS: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.

A novel HNF1B mutation p.R177Q in autosomal dominant tubulointerstitial kidney disease and maturity-onset diabetes of the young type 5: A pedigree-based case report.

RATIONALE: Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene result in a very variable presentation, including maturity onset diabetes of the young (MODY), renal cysts, renal dysplasia, and autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by tubular damage, renal fibrosis, and progressive renal dysfunction. PATIENT CONCERNS: A 22-year-old man came to the hospital presenting with hyperglycemia, hyperuricemia and elevated serum creatinine. His urine protein was within the normal range. The ultrasound examination revealed shrunken kidneys with renal cysts. The patient's mother was diagnosed with diabetes mellitus when she was 25 years old. Her laboratory results showed elevated serum creatinine. Her ultrasonography revealed shrunken kidneys with renal cysts and hydronephrosis without kidney stones. The next-generation sequencing revealed that the proband and his mother held the same heterozygous missense mutation (c.530G>A, NM_000458, p.R177Q) in the HNF1B gene. Bioinformatic analyses predicted that the mutation was likely pathogenic. DIAGNOSIS: The patient and his mother were diagnosed as ADTKD and MODY5 due to HNF1B mutation. INTERVENTION: The proband was administered metformin at a dose of 500 mg/day. OUTCOMES: The patient had well-controlled blood glucose levels and a stable renal function at his 12-month follow-up. LESSONS: We should take into account the diagnoses of ADTKD and MODY5 if patients present with early onset diabetes and multiple renal cysts or evidence of renal tubulointerstitial dysplasia, especially those with negative proteinuria results. Genetic testing helps detect the HNF1B gene mutations.

Consideraciones bucodentales en pacientes con Síndrome de Morquio / Dental considerations of the morquio síndrome

La mucopolisacaridosis tipo IV (MPS-IV) también conocida como enfermedad de Morquio en recuerdo del pediatra uruguayo Luis Morquio que la describió por primera vez, es una enfermedad congénita causada por la deficiencia de la enzima N-acetilgalactosamina 6 sulfatasa o de la enzima B-Galactosidasa. Estas anomalías enzimáticas tienen como consecuencia que se acumulen en diferentes tejidos del organismo cantidades elevadas de mucopolisacaridos. En la bibliografía se describe con detalle los defectos del esmalte que presentan los pacientes diagnosticados del síndrome de Morquio. Estos defectos son una característica aparentemente constante en la enfermedad y, por lo tanto, hace necesaria las visitas al odontólogo para su control evitándose problemas mayores. Dichos defectos consisten en un esmalte anormalmente delgado, que es áspero debido a los numerosos hoyos diminutos y a una superficie irregular. La delgadez del esmalte da como resultado una forma alterada y decoloración de los dientes que, añadido a los diastemas interdentales, provocan alteraciones en la oclusión. Aparte de estos defectos, el esmalte es histológicamente normal y tiene una du-reza y radiodensidad normales. El trata-miento odontológico de los pacientes con MPS-IV requiere colaboración multidisciplinar, debido a que las manifestaciones orales de la enfermedad pueden aparecer a cualquier edad, resultando en ocasiones tedioso para el paciente y complicado para el profesional. Especial mención merecen las terapias utilizadas como trata-miento sintomático de la enfermedad, así como el manejo de la vía aérea en el caso de intervenciones bajo anestesia general o sedación para tratar ciertas patologías del territorio bucomaxilodental

Mucopolysaccharidosis type IV (MPS-IV) also known as Morquio’s disease in memory of the Uruguayan pediatrician Luis Morquio who described it for the first time, is a congenital disease caused by the deficiency of the enzyme N-acetylgalactosamine 6 sulfatase or enzyme B -Galactosidase. These enzymatic anomalies result in high amounts of mucopolysaccharides accumulating in different tissues of the organism. The enamel defects presented by patients diagnosed with Morquio syndrome are described in detail in the bibliography. These defects are an apparently constant feature in the disease and, therefore, make visits to the dentist necessary for their control, avoiding major problems. These defects consist of an abnormally thin enamel that is rough due to numerous tiny holes and an irregular surface. The thinness of the enamel results in an altered form and discoloration of the teeth, which added to the interdental diastemas, cause alterations in the occlusion. Apart from these defects, the enamel is histologically normal and has a normal hardness and radiodensity.Dental treatment of patients with MPS-IV requires multidisciplinary collaboration, because the oral manifestations of the disease can appear at any age, being sometimes tedious for the patient and complicated for the professional. Special mention should be made of the therapies used as a symptomatic treatment of the disease, as well as the management of the airway in the case of interventions under general anesthesia or sedation to treat certain pathologies of the bucomaxillodental territory

Use of Antibiotics in early Childhood and Dental Enamel Defects in 6- to 12-year-old Children in Primary Health Care.

Dental enamel defects (DED) are lesions that occur due several factors. Proper care is needed to promote their treatment and prevention. The aim of this study was to evaluate the occurrence of DED in permanent teeth of children who used antimicrobial drugs in the first four years of life. This is a crosssectional study carried out in a Primary Health Care (PHC) service, which included children from six to 12 years of age. DED were evaluated by oral examination, and data on the use of antimicrobials in early childhood were collected based on medical records. Data were analyzed with the chi-square test and Fisher's exact test. The sample included 144 children. In relation to DED, 50% (72) and 20.1% (29) presented opacity and hypoplasia, respectively. Amoxicillin was the most frequently prescribed drug, followed by sulfamethoxazole + trimethoprim. Among the children, 78.5% (113) were prescribed antimicrobial drugs at least once during the first 4 years of life, and 55% (79) of them presented some type of DED. There was no statistically significant association between the variables analyzed. In conclusion, there was high prevalence of children with DED, and amoxicillin was the most commonly prescribed antibiotic.

Os defeitos do esmalte dentário (DED) são lesões que ocorrem devido a vários fatores e é necessária atenção para promover seu tratamento e prevenção. O objetivo foi avaliar a ocorrência de DED em dentes permanentes de crianças que usaram antimicrobianos nos primeiros quatro anos de vida. Tratase de um estudo transversal realizado em um serviço de Atenção Primária à Saúde (APS), que incluiu crianças de seis a 12 aos de idade. A DED foi avaliada por dados de exames bucais, e os dados sobre o uso de antimicrobiano na primeira infância foram coletados com base em prontuários médicos. A análise foi realizada com o teste do qui-quadrado e o teste exato de Fisher. A amostra foi composta por 144 crianças. Em relação ao DED, 50%(72) e 20,1%(29) apresentaram opacidade e hipoplasia, respectivamente. A amoxicilina foi o medicamento prescrito com mais freqüência, seguido pelo sulfametoxazol+trimetoprim. Entre as crianças, 78,5%(113) receberam medicamentos antimicrobianos pelo menos uma vez nos primeiros 4 anos de vida e 55%(79) deles apresentaram algum tipo de DED. Não houve associação estatisticamente significante entre as variáveis analisadas. Em conclusão, houve uma alta prevalência de crianças com DED e a amoxicilina foi o antibiótico mais comumente prescrito.