Russell-Silver Syndrome With Growth Hormone Deficiency.

Russell-Silver syndrome (RSS) is a rare genetic disorder characterized by intrauterine growth restriction (IUGR), postnatal growth failure, and distinctive dysmorphic features. We present a case of a four-year-old male presenting with a slow growth velocity with a history of IUGR and surgical interventions, exhibiting classic RSS features. Laboratory investigations revealed low insulin-like growth factor 1 (IGF-1) and low growth hormone (GH) levels on stimulation tests. Clinical exome sequencing revealed a de novo mutation in the insulin-like growth factor 2 (IGF2) gene. Additionally, a variant of uncertain significance in the DHX37 gene was noted in the patient and the asymptomatic father. After genetic counseling, recombinant GH therapy was initiated. This case underscores the genetic complexity of RSS and highlights the importance of early diagnosis, genetic testing, and multidisciplinary management in optimizing outcomes for patients with RSS.

Erratum to Correct Informed Patient Consent Statement.

[This corrects the article DOI: 10.17925/EE.2023.19.2.6.].

Parathyroid Carcinoma Presenting as Recurrent Primary Hyperparathyroidism and Neck Mass: A Case Report.

Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.

Novel homozygous leptin receptor mutation in an infant with monogenic obesity.

Monogenic obesity can be caused by a mutation in one of the single genes involved in hunger and satiety. The most common mutations affect melanocortin 4 (MC4) followed by the leptin gene and its receptor. Leptin receptor (LEPR) gene mutation is an extremely rare endocrine disease characterized by early-onset obesity, hyperphagia in addition to pituitary hormone deficiency, and metabolic abnormalities. We report the case of a 12-month-old male infant born of a non-consanguineous marriage. He presented to us with rapid weight gain from 2 months of age along with hyperphagia. Biochemistry revealed a deranged lipid profile, elevated transaminases, and markedly raised serum leptin levels. On genetic analysis, a novel mutation was detected, which was a homozygous variation In exon 12 of the LEPR gene (chr1:g.65608901G>A) that resulted in the synonymous amino acid change of lysine at codon 584 proximal to donor splice site (p.Lys584). The in silico prediction of the variant was 'damaging' by MutationTaster2. The mutation was classified as a 'variant of uncertain significance' due to a lack of published literature and had to be correlated carefully with the clinical symptoms. It was recommended to do Sanger sequencing of the parents and other family members. However, due to financial constraints, the family could not afford the same. At the time of writing, funds were being arranged for procuring setmelanotide, which is a novel and effective therapy for monogenic obesity due to LepR mutation.

Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.

Epigenetics of type 2 diabetes mellitus (T2DM) has widened our knowledge of various aspects of the disease. The aim of this review is to summarize the important epigenetic changes implicated in the disease risks, pathogenesis, complications and the evolution of therapeutics in our current understanding of T2DM. Studies published in the past 15 years, from 2007 to 2022, from three primary platforms namely PubMed, Google Scholar and Science Direct were included. Studies were searched using the primary term 'type 2 diabetes and epigenetics' with additional terms such as 'risks', 'pathogenesis', 'complications of diabetes' and 'therapeutics'. Epigenetics plays an important role in the transmission of T2DM from one generation to another. Epigenetic changes are also implicated in the two basic pathogenic components of T2DM, namely insulin resistance and impaired insulin secretion. Hyperglycaemia-i nduced permanent epigenetic modifications of the expression of DNA are responsible for the phenomenon of metabolic memory. Epigenetics influences the development of micro-and macrovascular complications of T2DM. They can also be used as biomarkers in the prediction of these complications. Epigenetics has expanded our understanding of the action of existing drugs such as metformin, and has led to the development of newer targets to prevent vascular complications. Epigenetic changes are involved in almost all aspects of T2DM, from risks, pathogenesis and complications, to the development of newer therapeutic targets.

Diabetic Cheiroarthropathy in Type 1 Diabetes Mellitus and Coeliac Disease.

Diabetes mellitus can be associated with a variety of musculoskeletal disorders. Diabetic cheiroarthropathy or diabetic hand syndrome is one of the complications encountered in long-standing uncontrolled diabetes. It is characterized by limited movement of the joints of the hands along with thickening of the skin on the palmar and dorsal surfaces. There is an association between diabetic cheiroarthropathy and microvascular complications of diabetes, most commonly diabetic retinopathy. Early diagnosis of cheiroarthropathy can give the clinician an opportunity to screen for microvascular complications. Cheiroarthropathy is usually a clinical diagnosis. Treatment involves achievement of good glycemic control along with physiotherapy and occupational therapy. We have described the case of a 16-year-old adolescent male with uncontrolled type 1 diabetes and coeliac disease who presented to us with diabetic cheiroarthropathy.