Bright and enlarged fetal kidneys: One phenotype different genotypes, and counseling dilemmas.

INTRODUCTION: In the present study we describe atypical cases with bright and enlarged fetal kidneys identified on fetal ultrasound with different genetic etiologies. METHODS: Exome sequencing was undertaken after prenatal counseling and after the initial diagnosis of enlarged fetal kidneys was made on ultrasound for four cases and the results were then correlated. RESULTS: In the present study we identified underlying variants in ACE, ETFA, PKD1, and MKS1 gene where the atypical presentation of fetal kidneys was noted either as a part of spectrum of syndrome or alone. CONCLUSIONS: In the era of exome sequencing, targeted gene sequencing is getting replaced and for better. However not all answers are direct, and sometimes the variant categorization is dependent on the acumen and agreement of all those involved in the process. It includes those involved the diagnostic as well those catering to the patients. It is very important to be updated on the relevance of multiple gene in causing similar phenotypes particularly in the prenatal context were coming up with a timely diagnosis is very important for any sort of intervention.

Revisiting Utility of Fetal Autopsy in Genomic Era.

Background: Autopsy has been a gold standard in cases of antenatal detected anomalies or fetal demise. This helped clinicians in getting insights into the future management. In current times, ultrasound and genomic testing has become extremely powerful in further refining the etiological basis; however, fetal autopsy still has its role even now. Material and Methods: We have discussed the utility of fetal autopsy in current times by diving the cases in seven groups. Results: Case based discussions to discuss the utility of fetal autopsy. Conclusions: We suggest that fetal autopsy should be the standard of care in case of any abnormal fetal outcomes alongwith fetal genomic testing. Fetal autopsy is complementary to the ultrasound assessment and genomic investigations in reaching the final diagnosis and provides invaluable information regarding recurrence risk which may not be available when couple plans next pregnancy.

Reusable Cobalt-Catalyzed Selective Transfer Hydrogenation of Azoarenes and Nitroarenes.

Herein, control transfer hydrogenation (TH) of azoarenes to hydrazo compounds is established employing easy-to-synthesize reusable cobalt catalyst using lower amounts of N2H4·H2O under mild conditions. With this effective methodology, a library of symmetrical and unsymmetrical azoarene derivatives was successfully converted to their corresponding hydrazo derivatives. Further, this protocol was extended to the TH of nitroarenes to amines with good-to-excellent yields. Several kinetic studies along with Hammett studies were carried out to understand the plausible mechanism and the electronic effects in this transformation. This inexpensive catalyst can be recycled up to five times without considerable loss of catalytic activity.

Spectrum of fetal limb anomalies.

PURPOSE: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk. METHODS: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies. RESULTS: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified. CONCLUSION: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal.

A myriad of posterior fossa cysts: A single center experience.

Antenatal posterior fossa cystic lesions are intimidating due to overlapping imaging features of benign and severe malformations. Sonographic assessment of the posterior fossa with good resolution median sagittal and axial views, either primary or secondarily reconstructed, plays the lead role in antenatal evaluation, further enhanced when sequential assessments are added. We present 10 cases of fetal posterior fossa cystic lesions diagnosed in the first and second trimesters that were sequentially analyzed and followed up till delivery or termination. The ultrasound imaging appearance, evolution, and morphometry have been presented in this article.

Revisiting absent nasal bone in the second trimester.

PURPOSE: To evaluate the outcomes of fetuses diagnosed with absent nasal bone in the second trimester. METHODS: This prospective, observational study included all fetuses who were diagnosed at or referred to our fetal medicine center with an absent nasal bone from 16 weeks onwards from November 2017 to December 2019. Amniocentesis for fetal karyotype and microarray was offered to all women. Women who opted not to undergo invasive testing were also followed up and neonatal outcome noted. RESULTS: 26 fetuses were eligible for inclusion in the study. 8 (30.8%) out of these were diagnosed with aneuploidy: 7 with trisomy 21 and one with trisomy 18. All fetuses with aneuploidy had additional ultrasound abnormality and/or high risk on biochemical screening. CONCLUSIONS: Isolated absent nasal bone in the second trimester with prior low risk on combined screening performed by certified sonographers is unlikely to be associated with Down syndrome.

Isolated Fetal Ascites: Etiology and Prognosis - A 10-Year Experience from a Tertiary Referral Care Center in India.

INTRODUCTION: Isolated fetal ascites is an uncommon finding, and it may be difficult to elucidate the underlying pathology. This is more so when there are limited resources to investigate the patient adequately. This study was undertaken to see the etiology of isolated fetal ascites and analyze the outcomes. MATERIALS AND METHODS: Twenty-three cases of isolated fetal ascites were retrospectively analyzed from December 2007 to June 2018. All cases were investigated with detailed ultrasound with other investigations as required. Postnatal data included gestational age at birth, mode of delivery, weight, and postnatal outcome. RESULTS: The mean age at diagnosis was 26 gestational weeks. Structural abnormalities without any underlying chromosomal or genetic cause were identified in 10/23 (43.4%) cases with the most common structural abnormality related to the gastrointestinal tract where ultrasound proved to the most useful tool. The overall good prognosis was seen in 13/23 (56.5%) cases. CONCLUSION: Appropriate perinatal care, timely referral and delivery at tertiary care setup, and timely surgical intervention are measures which can improve the outcome and survival in fetuses diagnosed with isolated fetal ascites.

Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia.

Hereditary spastic paraplegias (HSPs) are genetically and clinically heterogeneous axonopathies primarily affecting upper motor neurons and, in complex forms, additional neurons. Here, we report two families with distinct recessive mutations in TFG, previously suggested to cause HSP based on findings in a single small family with complex HSP. The first carried a homozygous c.317G>A (p.R106H) variant and presented with pure HSP. The second carried the same homozygous c.316C>T (p.R106C) variant previously reported and displayed a similarly complex phenotype including optic atrophy. Haplotyping and bisulfate sequencing revealed evidence for a c.316C>T founder allele, as well as for a c.316_317 mutation hotspot. Expression of mutant TFG proteins in cultured neurons revealed mitochondrial fragmentation, the extent of which correlated with clinical severity. Our findings confirm the causal nature of bi-allelic TFG mutations for HSP, broaden the clinical and mutational spectra, and suggest mitochondrial impairment to represent a pathomechanistic link to other neurodegenerative conditions.

Novel ATRX gene damaging missense mutation c.6740A>C segregates with profound to severe intellectual deficiency without alpha thalassaemia.

BACKGROUND & OBJECTIVES: ATRX is a recessive X-linked intellectual deficiency (X-LID) gene causing predominately alpha-thalassaemia with a wide and clinically heterogeneous spectrum of intellectual deficiency syndromes. Although alpha-thalassaemia is commonly present, some patients do not express this sign despite the ATRX gene being altered. Most pathological mutations have been localized in two different major domains, the helicase and the plant homeo-domain (PHD)-like domain. In this study we examined a family of three males having an X-linked mental deficiency and developmental delay, and tried to establish a genetic diagnosis while discussing and comparing the phenotype of our patients to those reported in the literature. METHODS: Three related males with intellectual deficiency underwent clinical investigations. We performed a karyotype analysis, CGH-array, linkage study, and X-exome sequencing in the index case to identify the genetic origin of this disorder. The X-inactivation study was carried out in the mother and Sanger sequencing was achieved in all family members to confirm the mutation. RESULTS: a0 novel ATRX gene missense mutation (p.His2247Pro) was identified in a family of two uncles and their nephew manifesting intellectual deficiency and specific facial features without alpha-thalassaemia. The mutation was confirmed by Sanger sequencing. It segregated with the pathological phenotype. The mother and her two daughters were found to be heterozygous. INTERPRETATION & CONCLUSIONS: The novel mutation c.6740A>C was identified within the ATRX gene helicase domain and confirmed by Sanger sequencing in the three affected males as well as in the mother and her two daughters. This mutation was predicted to be damaging and deleterious. The novel mutation segregated with the phenotype without alpha-thalassaemia and with non-skewed X chromosome.

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure.

Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration.

Approach to the diagnosis of skeletal dysplasias: Experience at a center with limited resources.

PURPOSE: A fetus with skeletal disorder poses diagnostic challenges in a resource-poor setting with limited management options. The objective of the study was to develop a step-by-step approach for the diagnosis of skeletal dysplasia in light of the limited resources available. METHODS: An algorithmic approach was used. The assessment for lethality was the first step, followed by the evaluation for fractures. In cases without evidence of fracture, severe constriction of thorax or associated polydactyly were searched for. In cases without severe thoracic constriction, the severity of micromelia was evaluated. After delivery, fetal examination was done to ascertain the etiology. RESULTS: During the 6-year period, 41 cases with shortened long bones were fully evaluated. Lethality was suspected in 30 cases. Fracture and beading were present in eight cases, and severe thoracic constriction with polydactyly was observed in seven cases. Mild micromelia was seen in 19 cases and severe micromelia in 7 cases. Among lethal skeletal dysplasias, thanatophoric dysplasia was most common (six cases). Among nonlethal skeletal dysplasias, achondroplasia was seen in eight cases. CONCLUSIONS: Lethality of skeletal dysplasia could be predicted on prenatal ultrasound with 100% accuracy. The step-by-step approach was helpful to characterize skeletal dysplasias. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:529-539, 2016.

Mandibular Interincisor and Intercanine Width at Three Different Stages of Dentition: A Cross-sectional Study.

Background and objective: Malocclusion is a manifestation of normal biological variability, defined as a misalignment of the teeth or an incorrect occlusion between the upper and lower dental arches. This study aimed to evaluate the mandibular intercanine primary, mixed, and permanent dentition in school children of Shimla, Himachal Pradesh. Materials and methods: This cross-sectional study was conducted on 1,392 children between the ages of 4 and 18 years from schools that fulfilled the inclusion criteria. The dental casts were poured and further divided based on the dentition stage, i.e., primary, mixed, and permanent dentition stages. Mandibular arch widths-interincisor and intercanine were measured on the casts by a digital vernier caliper. Results: The statistically significant difference was found as the interincisor width increased from primary to mixed dentition and between males and females for permanent dentition. Intercanine width significantly increases from primary to mixed dentition and gradually from mixed to permanent dentition stages. Conclusion: The present study found that there is a significant increase in interincisor and intercanine width in the lower dental arch from primary dentition to permanent dentition. How to cite this article: Singhal P, Jaswal O, Thakur S. Mandibular Interincisor and Intercanine Width at Three Different Stages of Dentition: A Cross-sectional Study. Int J Clin Pediatr Dent 2024;17(4):417-424.

Comparative Evaluation of Clinical Instrumentation Time and Quality of Obturation of Two Different Pedo Rotary File Systems in Primary Mandibular Molars: An In Vivo Study.

Introduction: The preferred treatment for primary teeth that are necrotic has been pulpectomy. Despite being the gold standard for years, using hand files can be difficult because of the longer chairside periods. Technology advancements have made it possible to reduce the need for manual dexterity and enhance pulpectomy care. Pediatric rotary files are now available specifically for use with primary teeth. This study's goal was to assess and contrast the instrumentation time and obturation quality of manual H files and pediatric rotary file systems (Prime Pedo™ and DXL-Pro™ rotary file systems) in primary mandibular molars. Materials and methods: A total of 51 deciduous mandibular molars that were evenly distributed for instrumentation were subjected to pulpectomy. Group I included the Prime Pedo™ rotary file system, group II included the DXL-Pro™ rotary file system, and group III included manual H files. A stopwatch was used to record the instrumentation time, and a postoperative radiograph was used to record the obturation quality. Results: When comparing pediatric rotary file systems to manual H files, there was a statistically significant reduction in instrumentation time (p = 0.000). When comparing the pediatric rotary file systems to the manual H files, there was no discernible difference in the obturation quality (p = 0.534). Conclusion: In all three file groups, the quality of obturation produced results that were comparable. On the other hand, a significant difference was observed in the instrumentation time between rotary and manual instrumentation for deciduous teeth. How to cite this article: Thakur S, Dhanasekaran M, Singhal P. Comparative Evaluation of Clinical Instrumentation Time and Quality of Obturation of Two Different Pedo Rotary File Systems in Primary Mandibular Molars: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(3):303-306.

Phosphofurin Acidic Cluster Sorting Protein 1 Syndrome: Insights Gained on the Multisystem Involvement Reviewing Encoded Protein Interactions?

Mutations in PACS1 cause moderate-to-severe intellectual disability. Very few cases of PACS1 neurodevelopment disorder have been described in the literature that were identified using whole exome sequencing (WES). We report a case of de novo PACS1 mutation identified through WES after an initial workup for mucopolysaccharidosis. Through this case, we wish to emphasize that most important clinical clue in the facial gestalt is a downturned angle of mouth, thin lips, and wide mouth, giving characteristic wavy appearance of face that can distinguish these cases and can prevent unnecessary workup for the patients.

An Unusual Case of Mesial Supplementary Lateral Incisor: A Case Report.

By definition, supplemental teeth are supernumerary teeth (ST) resembling adjacent teeth at the end of a tooth series and are well aligned in the arch. A case of the non-syndrome, supplemental type of supernumerary lateral incisor is presented, along with an unusual habit that was noted accidentally in the same child. In the present case, of the two lateral incisors, the mesial supplemental lateral incisor was causing an impaction of 11. In addition, the patient was aesthetically concerned. So, the decision was made to extract the supplemental tooth with altered morphology (mesial one) under local anesthesia even though, as per definition, the distal one is the supplementary tooth. And finally, to align the incisors by orthodontic treatment. Aim: A case of the non-syndrome, supplemental type of supernumerary lateral incisor is presented, along with an unusual habit of that was noted accidentally in the same child. Background: By definition, supplemental teeth are supernumerary teeth (ST) resembling adjacent teeth at the end of a tooth series and are well aligned in the arch. Case description: In the present case, of the two lateral incisors, the mesial supplemental lateral incisor was causing impaction of 11. In addition, the patient was aesthetically concerned. Conclusion: Decision was made to extract the supplemental tooth with altered morphology (mesial one) under local anesthesia even though, as per definition, the distal one is the supplementary tooth. And finally, to align the incisors by orthodontic treatment. Clinical significance: Decision-making regarding removal of tooth is quite baffling as a selective removal of the normal or the supplementary tooth may be required and it should be made after analyzing multiple factors. How to cite this article: Sojan M, Thakur S. An Unusual Case of Mesial Supplementary Lateral Incisor; A Case Report. Int J Clin Pediatr Dent 2023;16(3):518-521.

Neu-Laxova's Syndrome: A Case Report of a Fetus with Novel Mutation in PHGDH Gene and a Literature Review.

Neu-Laxova's syndrome (NLS) is a rare group of congenital malformations comprising intrauterine growth retardation (IUGR), central nervous system malformations, microcephaly, facial anomalies, ichthyosis, generalized edema, limb abnormalities, polyhydramnios, and perinatal death. We hereby report a fetus at 25 weeks' gestation with IUGR, facial and limb anomalies, and smooth brain detected on antenatal ultrasound and magnetic resonance imaging of fetus and confirmed by autopsy. Next-generation sequencing analysis identified a novel homozygous missense mutation in PHGDH gene. Only 35 cases of NLS with genetic etiology have been reported. This is the first case report of mutation in PHGDH from India.

Prenatal sonographic evaluation and postnatal outcome of renal anomalies.

OBJECTIVE: To determine the prognosis of antenatally detected renal anomalies by sonographic evaluation. MATERIALS AND METHODS: This was a follow-up study of all antenatally detected renal anomalies from January 2008 to Dec 2009 referred to fetal medicine clinic. Prenatal evaluation was done and cases were divided into four groups depending upon their prenatal sonographic findings. Post natal follow-up was done up to one year in cases of live babies. Autopsy was carried out in still born fetus after consent. RESULTS: The renal anomaly was detected in 55 cases, which were fully followed. The prognosis was said to be poor for group I cases with gross extra renal anomaly along with the renal anomaly, and for group II in which there was organic renal pathology with loss of renal function suggested by non-visualization of bladder and almost absent liquor. Prognosis was guarded and depended upon the gestational age of presentation in group III, which had obstructive uropathy; prognosis was good in group IV cases, which were mild, unilateral or which presented late. CONCLUSION: Prenatal sonographic evaluation gives reasonably accurate picture of the prognosis and can be very helpful in counseling the parents regarding prognosis and help in deciding the timing and route of delivery.

Changes in nasal symmetry after presurgical nasoalveolar molding in infants treated with complete unilateral cleft lip and palate: A follow-up study.

Background: A significant improvement in the nasal symmetry after presurgical nasoalveolar molding (PNAM) is seen in complete unilateral cleft lip and palate (UCLP) infants. However, the follow-up changes in the nasal symmetry before and after PNAM and surgical repair have not been well documented. Materials and Methods: The purpose of this retrospective study is to assess the progressive changes in the nasal symmetry after PNAM and primary cheiloplasty to 1 year in complete UCLP infants. Out of 28 complete UCLP patients who were given PNAM treatment during the period between January 2014 to March 2019, 19 UCLP infants could be included for the study. Submental oblique photographs at the initial visit (T1), immediately after cheiloplasty (T2), and 1 year (T3) after cheiloplasty were selected, and quantity of nasal asymmetry at each period (T1-T2; T1-T3; and T2-T3) was analyzed by paired t-test (P < 0.05). Results: The quantity of asymmetry revealed that there was a highly significant improvement (P < 0.001) in nasal asymmetry at T1-T2 and T1-T3. Nonsignificant relapse was observed at T2-T3; however, a significant relapse in nasal dome height was observed during this period. Conclusion: The improvement in the nasal symmetry after cheiloplasty in PNAM-treated patients is maintained till 1 year postsurgically though there is a nonsignificant relapse.

A Comparative Study to Evaluate the Effectiveness of Silver Diamine Fluoride at Different Time Durations of Application in Treating Carious Primary Teeth: A Randomized Trial.

Background and objectives: Ideally every child must have access to preventive and restorative care of greater quality. However, in rural areas, resources and dental care services are limited. Silver diamine fluoride (SDF) has been identified as an efficient topical cariostatic and preventive medicament for managing ECC in children who cannot be treated conventionally. Since SDF is an emerging alternative for caries prevention and arrest, AAPD recommends more practice-based research to evaluate its efficacy. The aim of this study was to evaluate the effectiveness of silver diamine fluoride at different time durations of application in treatment of carious primary teeth in children with least access to dental care. Methodology: This was a prospective, randomized, field trial that included patients with primary tooth. Primary tooth presenting carious lesion in ICDAS 3-6 category were randomly assigned to one of the three groups. Results: At 3-week mean rank of lesions arrested in Group 1 and Group 2 were 73.3 and 72.29, whereas it was 86.9 in case of Group 3. At 6 months it was 79.15, 77.29, and 75.96 in Group 1, 2, and 3, respectively (p > 0.05). Conclusion: SDF is effective in controlling caries progression in both cavitated and non-cavitated lesion with minimal time duration of application (30 seconds). This approach may be of great utility as an alternative to other expensive preventive and therapeutic methods in communities with limited resources. Nonetheless obtaining caregiver consent is mandatory. How to cite this article: Thakur S, Sojan M, Singhal P, et al. A Comparative Study to Evaluate the Effectiveness of Silver Diamine Fluoride at Different Time Durations of Application in Treating Carious Primary Teeth: A Randomized Trial. Int J Clin Pediatr Dent 2022;15(S-2):S147-S150.