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International Journal of Molecular... May 2024Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians.... (Review)
Review
Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.
Topics: Humans; Megalencephaly; Fingers
PubMed: 38791606
DOI: 10.3390/ijms25105567 -
International Journal of Surgery Case... Jun 2024Beckwith-Wiedemann syndrome (BWS) manifests distinctive features, such as macroglossia, overgrowth, and abdominal wall defects. In this report, we describe a case of BWS...
INTRODUCTION
Beckwith-Wiedemann syndrome (BWS) manifests distinctive features, such as macroglossia, overgrowth, and abdominal wall defects. In this report, we describe a case of BWS in an extremely low birth weight infant diagnosed at three months after birth because of the intensive care for low birth weight.
PRESENTATION OF CASE
A female infant was delivered at 24 weeks and 6 days of gestation with a weight of 845 g. After birth, significant small intestinal intra-umbilical prolapse was observed, and abdominal wall closure using a sutureless method was performed on day zero. Careful neonatal management was performed; however, an episode of bloody stools led to a diagnosis of intestinal volvulus due to intestinal malrotation. At 119 days of age, the Ladd procedure was performed. Notably, during anaesthesia induction, features suggestive of BWS were observed, leading to its diagnosis.
DISCUSSION
Early diagnosis of BWS is vital because of its association with tumors. However, because she was an extremely low birth weight infant who required oral intubation and supine management for respiratory control, nevus flammeus and macroglossia were not observed. Therefore, BWS was not diagnosed for approximately three months after birth. It is important to recognize that omphalocele in extremely low birth weight infants is a risk factor for delayed diagnosis of BWS.
CONCLUSION
Timely diagnosis of BWS is critical because of its association with tumors and varied clinical presentations. Early screening, especially for tumors, and awareness among surgical practitioners can aid in timely interventions and improved patient outcomes.
PubMed: 38781840
DOI: 10.1016/j.ijscr.2024.109777 -
Autopsy & Case Reports 2024Trisomy 13, known as Patau syndrome, is a common aneuploidy with a well-known clinical phenotype. This case report describes a trisomy 13 patient with unusual autopsy...
Trisomy 13, known as Patau syndrome, is a common aneuploidy with a well-known clinical phenotype. This case report describes a trisomy 13 patient with unusual autopsy findings, including features resembling the Beckwith-Wiedemann Spectrum. Due to abnormalities of gestational ultrasounds, a prenatal karyotype of amniotic fluid cells was performed, which resulted in 47, XY+13. Autopsy microscopy studies identified leptomeningeal glioneuronal heterotopia, which was not described as belonging to Patau syndrome. Other atypical findings were diffuse hyperplasia of pancreatic islets of Langerhans and adrenals enlargement with marked adrenocortical cytomegaly, characteristically seen in the Beckwith-Wiedemann Spectrum. Molecular genetic tests were not performed for the Beckwith-Wiedemann Spectrum. Still, due to the rarity of both disorders, this report may support the evidence that trisomy 13 can affect tissue organization and lead to unusual histopathologic features resembling classic overgrowth disorders.
PubMed: 38770437
DOI: 10.4322/acr.2024.486 -
Annual Review of Nutrition May 2024Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers... (Review)
Review
Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers obesity-related comorbidities. It also has significant physiological and nutritional consequences that can result in gastrointestinal complications and micronutrient deficiencies. After gastric bypass, common clinical events that negatively affect nutritional status include malabsorption, dumping syndrome, kidney stones, altered intestinal bile acid availability, bowel obstruction, ulcer, gastroesophageal reflux, and bacterial overgrowth. Risk factors for poor nutritional status and excessive loss of lean body mass and bone include reduced dietary quality and inadequate intake, altered nutrient absorption, and poor patient compliance with nutrient supplementation. There are unique concerns in adolescents, older individuals, and individuals who become pregnant postoperatively. With careful management, health-care professionals can assist with long-term weight loss success and minimize the risk of acute and long-term nutrition complications after bariatric surgery.
PubMed: 38768613
DOI: 10.1146/annurev-nutr-061121-101547 -
American Journal of Medical Genetics.... May 2024The Simpson-Golabi-Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait,... (Review)
Review
The Simpson-Golabi-Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait, with variable expressivity in males and reduced penetrance and expressivity in females. The clinical spectrum is broad, ranging from mild manifestations in both males and females to multiple malformations and neonatal death in the more severely affected cases. An increased risk of neoplasia is reported, requiring periodical surveillance. Intellectual development is normal in most cases. SGBS is caused by a loss-of-function mutation of the GPC3 gene, either deletions or point mutations, distributed all over the gene. Notably, GPC3 deletion/point mutations are not found in a significant proportion of clinically diagnosed SGBS cases. The protein product GPC3 is a glypican functioning as a receptor for Hh at the cell surface, involved in the Hh-Ptc-Smo signaling pathway, a regulator of cellular growth.
PubMed: 38766979
DOI: 10.1002/ajmg.c.32088 -
Ophthalmic Plastic and Reconstructive...We describe the first case reported in ophthalmological literature of the surgical management of a 17-month-old boy with bilateral vision-threatening ptosis,...
We describe the first case reported in ophthalmological literature of the surgical management of a 17-month-old boy with bilateral vision-threatening ptosis, tarsomegaly, ectropion, and euryblepharon secondary to suspected overgrowth syndrome. We elaborate on the major challenges associated with surgical management including the natural and asymmetric growth of oversized tissue, the high likelihood of scarring and formation of disorganized tissue, and risks of frequent intubation in these patients who may have lesions that compromise critical structures such as the airway. Ultimately, surgical intervention is encouraged primarily if vision or ocular health is threatened and secondarily to achieve good cosmesis.
Topics: Humans; Male; Blepharoptosis; Infant; Ophthalmologic Surgical Procedures; Eyelids; Syndrome; Oculomotor Muscles
PubMed: 38738723
DOI: 10.1097/IOP.0000000000002621 -
ArXiv Apr 2024Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible...
Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible answer over a prolonged period of time. Addressing this "diagnostic odyssey" thus has substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features, which can be used by artificial intelligence algorithms to facilitate clinical diagnosis, in prioritizing candidate diseases to be further examined by lab tests or genetic assays, or in helping the phenotype-driven reinterpretation of genome/exome sequencing data. Existing methods using frontal facial photos were built on conventional Convolutional Neural Networks (CNNs), rely exclusively on facial images, and cannot capture non-facial phenotypic traits and demographic information essential for guiding accurate diagnoses. Here we introduce GestaltMML, a multimodal machine learning (MML) approach solely based on the Transformer architecture. It integrates facial images, demographic information (age, sex, ethnicity), and clinical notes (optionally, a list of Human Phenotype Ontology terms) to improve prediction accuracy. Furthermore, we also evaluated GestaltMML on a diverse range of datasets, including 528 diseases from the GestaltMatcher Database, several in-house datasets of Beckwith-Wiedemann syndrome (BWS, over-growth syndrome with distinct facial features), Sotos syndrome (overgrowth syndrome with overlapping features with BWS), NAA10-related neurodevelopmental syndrome, Cornelia de Lange syndrome (multiple malformation syndrome), and KBG syndrome (multiple malformation syndrome). Our results suggest that GestaltMML effectively incorporates multiple modalities of data, greatly narrowing candidate genetic diagnoses of rare diseases and may facilitate the reinterpretation of genome/exome sequencing data.
PubMed: 38711434
DOI: No ID Found -
Archives of Medical Research Jun 2024Pituitary apoplexy (PA) is a clinical syndrome resulting from a hemorrhagic infarction of the pituitary gland. It is characterized by the sudden onset of visual... (Review)
Review
Pituitary apoplexy (PA) is a clinical syndrome resulting from a hemorrhagic infarction of the pituitary gland. It is characterized by the sudden onset of visual disturbances, nausea, vomiting, headache and occasionally, signs of meningeal irritation and an altered mental status. The exact pathogenesis of PA remains to be elucidated, although tumor overgrowth of its blood supply remains the most popular theory. Main risk factors for the development of PA include systemic, iatrogenic, and external factors as well as the presence of an underlying pituitary tumor. The diagnostic approach of PA includes both neuroimaging and evaluation of pituitary secretory function. PA is a potentially life-threatening condition which should be managed with hemodynamic stabilization, correction of electrolyte abnormalities and replacement of hormonal deficiencies. PA treatment should be individualized based on the severity of the clinical picture which may vary widely. Treatment options include conservative management with periodic follow-up or neurosurgical intervention, which should be decided by a multidisciplinary team. We conducted a systematic review of the literature to unveil the frequency of PA predisposing factors, clinical and biochemical presentations, management strategies and outcomes.
Topics: Pituitary Apoplexy; Humans; Risk Factors
PubMed: 38703639
DOI: 10.1016/j.arcmed.2024.103001 -
DNA and Cell Biology May 2024Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain...
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of but also enhances our understanding of the mechanisms connecting with overgrowth syndromes.
PubMed: 38700464
DOI: 10.1089/dna.2023.0391 -
The Journal of the Association of... Sep 2023The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress,... (Review)
Review
The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.
Topics: Humans; Anti-Bacterial Agents; Dysbiosis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Irritable Bowel Syndrome; Prebiotics; Probiotics
PubMed: 38700306
DOI: 10.59556/japi.71.0353