Loeys-Dietz syndrome and Goldenhar syndrome unveiled together.

Haemifacial microsomia is an asymmetrical congenital tissue malformation developed from the first and second branchial arches with or without multi-system involvement. Alternatively recognised as Goldenhar syndrome or oculoauriculovertebral spectrum (OAVS), it is an aetiologically heterogeneous group of disorders showing dominant trends in inheritable form.We present a case of a boy in early childhood with concomitant craniofacial features of craniofacial microsomia with Loeys-Dietz syndrome. He had a unilateral hypoplastic face, asymmetrical ear malformations and multiple preauricular tags with epibulbar dermoid (features suggestive of Goldenhar syndrome). On detailed clinical evaluation, he met Beighton's criteria and was diagnosed with arterial tortuosity. Further molecular testing confirmed the diagnosis of Loeys-Dietz syndrome type II.Loeys-Dietz syndrome is characterised by aortic root enlargement or type A dissection with or without other vascular malformations and facial midline defects. Molecular testing is required to establish the diagnosis because of overlapping features with other connective tissue disorders.

Thurston syndrome with thalassaemia: a rare case devising a novel molecular and phenotypic variation.

A male infant presented with progressive paleness of the body since 3 months of age. On examination, the child had pallor, microcephaly with dysmorphic facies (depressed nasal bridge, low set ears, retrognathia, high arched palate and tongue hamartoma). Postaxial polydactyly in bilateral hands and feet, broad great toes, with syndactyly of left fourth and fifth toes were present. The haemogram showed severe anaemia with a microcytic hypochromic picture. High-performance liquid chromatography (HPLC) was normal. However, the parents' HPLC was suggestive of beta thalassaemia trait. Whole-exome sequencing revealed Thurston syndrome with beta-thalassaemia in homozygous pattern with a novel mutation. It is a rare genetic syndrome exclusively found in the South Asian population. Due to the rarity, identification of this syndrome is often difficult and requires awareness among clinicians. However, it is important to diagnose the disorder accurately in order to provide appropriate genetic counselling and prognostication to the parents.

Prevalence and Associated Clinical Features of Type 1 Diabetes Mellitus Among Children Presented to a Tertiary Health Care Center of Himalayan Foothills.

Introduction Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia. Knowing its prevalence, associated clinical features, and complications is essential for diagnosing children having diabetes-like clinical features. Since there is a limited study from India and no similar study from this geographical part, the present study was carried out. Material and method It is a cross-sectional study, which includes children aged 1-18 years presented to the pediatric outpatient department (OPD), inpatient department (IPD), and emergency with clinical features of Type 1 Diabetes Mellitus (T1DM). The enrolled cases were assessed for confirmation of T1DM, and clinical features and associated complications were recorded in the case record form. Result A total of 218 children with clinical features of T1DM were enrolled, out of which 32 (14.7%) had T1DM. Among the 32 T1DM patients, 31 (96.9%) of the participants presented with polyuria, 29 (90.6%) had polydipsia, and 13 (40.6%) had polyphagia. Out of 32 children, 3 (9.38%) had diabetic neuropathy, and 1 (3.1%) had diabetic retinopathy. Conclusion We found that many children with diabetes have clinical features of T1DM and uncontrolled blood sugar. This emphasizes the need for early detection and treatment to prevent long-term complications.

Genetic Association and Role of Surgery for the Treatment of Lower Limb Deformities in Diastrophic Dysplasia: A Case Report.

INTRODUCTION: Diastrophic dysplasia (DTD) results from SCN26A2 gene mutation, with autosomal recessive inheritance and widely variable phenotype. The gene has been mapped to chromosome 5q32-q33.1. CASE REPORT: We present a case of a 4-year-old female with short stature, bilateral feet and knee deformity, and dysplastic facies. SCN26A2 mutations were seen in patient as well as parents. She underwent multiple orthopedic procedures involving metatarsals, gastrosoleus, and distal femur. Based on typical clinical features, DTD was suspected. Genetic studies of patient and parents provided the exact diagnosis in this case. CONCLUSION: Genetic diagnosis and family counseling are important caveat of management. Key features like ear abnormalities help to suspect diagnosis which requires a high index of suspicion. Associated bony and soft-tissue abnormalities of lower limb may require surgical intervention for improvement of gait, functions, and cosmesis.

Gross hematuria: A rare presentation of disseminated tuberculosis.

Tuberculosis (TB) is a multi-systemic disease instigated by Mycobacterium tuberculosis that can involve any organ. In any child presenting with clinical features involving multiple organ systems, TB forms an important differential. This holds particularly for endemic countries like India. Genitourinary TB (GUTB) comprises up to 27% of all extrapulmonary TB cases. We present an unusual presentation of disseminated TB involving kidneys and presenting as gross hematuria. 12-year-old girl, presented with recurrent episodes of gross hematuria of one-month duration. She received multiple packed cell transfusions for the same. She had chronic malnutrition. USG KUB with renal doppler was normal. Given persistent hematuria, CT urography was done which showed features suggestive of papillary necrosis with cystitis. Tubercular workup showed multiple opacities predominantly involving perihilar regions bilaterally on chest x-ray along with positive Mantoux test. Sputum for AFB was positive for tubercular bacilli. Urine samples were also sent for CBNAAT which showed TB bacilli sensitive to rifampicin. With a diagnosis of disseminated TB, antitubercular therapy (ATT) was started followed by cystoscopic resection of inflamed bladder wall tissue. Bladder mucosal biopsy confirmed caseating granulomas suggestive of tuberculous cystitis. The patient is doing well and symptom-free after completion of ATT.

A rare case of coexisting tuberculosis with hydatid disease from North India with review of literature.

Coexisting tuberculosis (TB) and hydatid disease in an immunocompetent individual is an extremely rare occurrence. Given the similarities in the clinical manifestations and morbidities of both, specific diagnosis in individuals coinfected with these is difficult. We, hereby present a case of a 17-year-old adolescent man diagnosed to be a coinfection of pulmonary TB with pulmonary and cardiac hydatid disease, with the review of cases having a similar presentation. The coexistence of these infections should be considered in endemic areas. Management can only be done by a multidisciplinary approach including surgical, microbiological, histopathological and radiological facilities. Complete surgical excision of the cyst is the treatment of choice and medical therapy for both aetiologies should be appropriate to achieve cure.

Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR.

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15-40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is -8.5 kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >-9.20 kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.

Genetic association of adipokine and UCP2 polymorphism with recurrent miscarriage among non-obese women.

The adipokines produced from adipose tissues influence energy homeostasis, resulting in alterations of the adipokine concentrations. This process may be associated with fertility impairment, resulting in recurrent miscarriage. The present study investigated whether there was any association between the UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms, namely leptin 2549 (C/A), adeponectin 276 (G/T) and 45 (T/G) and resistin 420 (C/G) in 200 non-obese recurrent miscarriage patients and 300 ethnically matched negative controls. These markers were studied using gene-specific PCR single specific primer and restriction fragment length polymorphism. For leptin 2549 and adeponectin 276, the A allele and G allele showed 3.42-fold (P=0.0001) and 1.36-fold (P=0.036) increased risk of recurrent miscarriage, respectively. Combined analysis of UCP2 45-bp indel and leptin 2549 showed U0-L0 and U1-L0 variants to be at 2- and 3-fold increased associative risk, respectively. Combined analysis of leptin 2549 and adeponectin 276 showed L0-D0 and L0-D1 variants to be at 2- and 4-fold increased associative risk, respectively. The combination U1-L0-D1-A1-R1 was 4.39-fold higher (P=0.0007) among recurrent miscarriage patients. In conclusion, the results highlight the role of the studied adipokine and UCP2 polymorphisms in recurrent miscarriage among the North Indian non-obese population. Pregnancy invokes a large shift in maternal metabolism. The normal concentrations of adipokines, which maintain the integrity of the hypothalamus-pituitary-gonadal axis, regular ovulatory processes and successful embryo implantation, are altered because of the influence of energy homeostasis, which in turn leads to fertility impairment and recurrent miscarriage of unknown aetiology. Recurrent miscarriage is reported in higher frequency among obese women. The UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms namely leptin 2549 (C/A), adeponectin 276 (G/T), adeponectin 45 (T/G) and resistin 420 (C/G) have been shown to be associated with obesity. Most of the adipokine-related studies done previously have taken into consideration the metabolic function and obesity. However, there exist very few studies to evaluate the role of adipokines in non-obese recurrent miscarriage with no cause of repeated pregnancy losses. The present study focused at evaluating the independent effect of these single-nucleotide polymorphisms in non-obese women undergoing recurrent miscarriage.