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Acta Bio-medica : Atenei Parmensis Sep 2019Congenital hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones. It occurs in 1:2000-4000 newborns. Common clinical features... (Review)
Review
Congenital hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones. It occurs in 1:2000-4000 newborns. Common clinical features include decreased activity and increased sleep, feeding difficulty, constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, distended abdomen with umbilical hernia, and hypotonia. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment, congenital hypothyroidism leads to severe intellectual deficit and short stature. Congenital hyperthyroidism occurs when the thyroid gland produces too much of the hormone thyroxine, which can accelerate body metabolism, causing unintentional weight loss and a rapid or irregular heartbeat. Hyperthyroidism is very rare and its prevalence is unknown. Common clinical features include unintentional weight loss, tachycardia, arrhythmia, palpitations, anxiety, tremor and sweating. Here we summarize the genes involved in congenital hypo- and hyperthyroidism and the tests we use for genetic analysis.
Topics: Congenital Hypothyroidism; Genetic Predisposition to Disease; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Hyperthyroidism
PubMed: 31577260
DOI: 10.23750/abm.v90i10-S.8765 -
Acta Haematologica 2020Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe... (Review)
Review
Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe organ dysfunction. Despite the etiological heterogeneity of systemic amyloidosis, the clinical manifestations of the different forms of amyloidosis largely overlap and depend upon the effected organ. The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific; therefore, establishing the diagnosis is difficult, and early diagnosis requires clinical suspicion. Light chain (AL) amyloidosis may present with highly specific signs such as macroglossia and periorbital purpura, but these signs are insensitive. Amyloidosis is still underdiagnosed, even though treatments are now available and are effective in improving patient's survival and quality of life. Cardiac amyloidosis is the major determinant of survival, and the earlier it is detected the better the survival. All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin. The aim of this review is to provide clinicians with knowledge about the signs and symptoms that raise the suspicion of amyloidosis, bearing in mind the importance of early diagnosis of this disease.
Topics: Amyloidosis; Animals; Diagnosis, Differential; Disease Susceptibility; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Organ Specificity; Phenotype
PubMed: 32340017
DOI: 10.1159/000506617 -
Nature Reviews. Endocrinology Apr 2018Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal... (Review)
Review
Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.
Topics: Beckwith-Wiedemann Syndrome; Consensus; DNA Copy Number Variations; DNA Methylation; Humans; Molecular Diagnostic Techniques; Neoplasms, Germ Cell and Embryonal; Polymorphism, Single Nucleotide; Prenatal Diagnosis; Reproductive Techniques, Assisted
PubMed: 29377879
DOI: 10.1038/nrendo.2017.166 -
Frontiers in Pediatrics 2019Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall... (Review)
Review
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall defects, macroglossia, neonatal hypoglycemia, and predisposition to embryonal tumors. It is associated with genetic and epigenetic changes on the chromosome 11p15 region, which includes two imprinting control regions. Here we review strategies for diagnosing and managing BWS and delineate commonly used genetic tests to establish a molecular diagnosis of BWS. Recommended first-line testing assesses DNA methylation and copy number variation of the BWS region. Tissue mosaicism can occur in patients with BWS, posing a challenge for genetic testing, and a negative test result does not exclude a diagnosis of BWS. Further testing should analyze additional tissue samples or employ techniques with higher diagnostic yield. Identifying the BWS molecular subtype is valuable for coordinating patient care because of the (epi)genotype-phenotype correlations, including different risks and types of embryonal tumors.
PubMed: 32039119
DOI: 10.3389/fped.2019.00562