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Head and Neck Pathology Mar 2021This article reviews odontogenic and developmental oral lesions encountered in the gnathic region of pediatric patients. The process of odontogenesis is discussed as it... (Review)
Review
This article reviews odontogenic and developmental oral lesions encountered in the gnathic region of pediatric patients. The process of odontogenesis is discussed as it is essential to understanding the pathogenesis of odontogenic tumors. The clinical presentation, microscopic features, and prognosis are addressed for odontogenic lesions in the neonate (dental lamina cysts/gingival cysts of the newborn, congenital (granular cell) epulis of the newborn, melanotic neuroectodermal tumor, choristoma/heterotopia, cysts of foregut origin), lesions associated with unerupted/erupting teeth (hyperplastic dental follicle, eruption cyst, dentigerous cyst, odontogenic keratocyst/keratocystic odonogenic tumor, buccal bifurcation cyst/inflammatory collateral cyst) and pediatric odontogenic hamartomas and tumors (odontoma, ameloblastic fibroma, ameloblastoma, adenomatoid odontogenic tumor, primordial odontogenic tumor). Pediatric odontogenic and developmental oral lesions range from common to rare, but familiarity with these entities is essential due to the varying management implications of these diagnoses.
Topics: Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Jaw Diseases; Male; Odontogenesis; Tooth Abnormalities
PubMed: 33723756
DOI: 10.1007/s12105-020-01284-3 -
The American Journal of Gastroenterology Feb 2015This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a... (Review)
Review
This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms, Hereditary Nonpolyposis; Disease Management; Gastrointestinal Neoplasms; Genetic Testing; Hamartoma Syndrome, Multiple; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 25645574
DOI: 10.1038/ajg.2014.435 -
Endocrine Reviews Mar 2023The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or...
The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.
Topics: Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Hypothalamic Diseases; Hypothalamus; Puberty; Ubiquitin-Protein Ligases
PubMed: 35930274
DOI: 10.1210/endrev/bnac020 -
American Journal of Human Genetics Feb 2022Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent...
Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification of NGLY1 deficiency, a congenital disorder of deglycosylation (CDDG) caused by loss of function of an enzyme involved in fOS metabolism, has elicited increased interest in fOS processing. The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we report the clinical, biochemical, and molecular features of six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1; the individuals are from four different families. These individuals exhibit dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Complementation experiments with isogenic MAN2C1-KO HAP1 cells confirm the pathogenicity of three of the identified MAN2C1 variants. We further demonstrate that MAN2C1 variants lead to accumulation and delay in the processing of fOSs in proband-derived cells. These results emphasize the involvement of MAN2C1 in human neurodevelopmental disease and the importance of fOS catabolism.
Topics: Adolescent; Alleles; Brain Stem; Cell Line, Tumor; Central Nervous System Cysts; Cerebellar Vermis; Child; Child, Preschool; Congenital Disorders of Glycosylation; Female; Fetus; Glycosylation; Hamartoma; Humans; Hypothalamus; Intellectual Disability; Leukocytes; Male; Mannose; Oligosaccharides; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; Polymicrogyria; Tongue; alpha-Mannosidase
PubMed: 35045343
DOI: 10.1016/j.ajhg.2021.12.010 -
Indian Journal of Dermatology,... 2022Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan... (Review)
Review
Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome/loose anagen hair, Legius syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and capillary malformation-arteriovenous malformation are the well-recognized RASopathies. These are characterized by multi-organ tumours and hamartomas. Some other features in common are facial dysmorphism, skeletal abnormalities, congenital heart disease, neurocognitive abnormalities and risk of various solid-organ and haematological malignancies. Some of the RASopathies are heterogeneous, caused by several gene mutations resulting in variations in phenotypes and severity ranging from mild to fatal. Significant phenotypic overlaps among different disorders, often makes it difficult to pinpoint a clinical diagnosis. Specific cutaneous manifestations are present in some of the RASopathies and are often the earliest clinical signs/symptoms. Hence, dermatologists contribute significantly as primary care physicians by identifying disorder-specific cutaneous lesions. However, diagnostic work-up and management of these disorders are often multidisciplinary. Confirmation of diagnosis is possible only by genetic mapping in each case. Genetic counseling of the patients and the affected families is an important component of the management. The aim of this review is description of cutaneous manifestations of RASopathies in the background of multi-system involvement to enable dermatologists a comprehensive and logical approach to work up and diagnose such patients in the absence of facility for specific molecular testing.
Topics: Costello Syndrome; Dermatologists; Ectodermal Dysplasia; Humans; Noonan Syndrome; ras Proteins
PubMed: 35138057
DOI: 10.25259/IJDVL_799_20 -
Journal of Pharmacy & Bioallied Sciences Apr 2015Genodermatoses are an inherited disorder, present with multisystem involvement. Help us to identify regular mutations and appalling skin diseases with recessive... (Review)
Review
Genodermatoses are an inherited disorder, present with multisystem involvement. Help us to identify regular mutations and appalling skin diseases with recessive inheritance. Genetic heterogeneity is very common, and molecular diagnosis requires a broad effort. Recurrent mutations in unrelated families were seen in families with xeroderma, Griscelli. It seems likely that eventually oligonucleotide arrays will replace most other methods for routine mutation scanning of the more common diseases and planned sequencing will be increasingly used for rarer diseases.
PubMed: 26015711
DOI: 10.4103/0975-7406.155903