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Annals of Laboratory Medicine May 2023
Topics: Humans; Child; Intellectual Disability; Haploinsufficiency; Chromosome Deletion; Syndrome; Phenotype
PubMed: 36544348
DOI: 10.3343/alm.2023.43.3.319 -
European Journal of Human Genetics :... Nov 2023PIK3CA pathogenic variants are responsible for a group of overgrowth syndromes, collectively known as PIK3CA-Related Overgrowth Spectrum (PROS). These gain-of-function...
PIK3CA pathogenic variants are responsible for a group of overgrowth syndromes, collectively known as PIK3CA-Related Overgrowth Spectrum (PROS). These gain-of-function variants arise postzygotically, and, according to time of onset, kind of embryonal tissue affected and regional body extension, give rise to heterogeneous phenotypes. PROS rarity and heterogeneity hamper the correct estimation of its epidemiology. Our work represents the first attempt to define the prevalence of PROS according to the established diagnostic criteria and molecular analysis and based on solid demographic data. We assessed the prevalence in Piedmont Region (Italy), including in the study all participants diagnosed with PROS born there from 1998 to 2021. The search identified 37 cases of PROS born across the 25-year period, providing a prevalence of 1:22,313 live births. Molecular analysis was positive in 81.0% of participants. Taking into account the cases with a detected variant in PIK3CA (n = 30), prevalence of molecularly positive PROS was 1:27,519.
Topics: Humans; Mutation; Growth Disorders; Phenotype; Class I Phosphatidylinositol 3-Kinases; Syndrome
PubMed: 37365400
DOI: 10.1038/s41431-023-01414-9 -
American Journal of Medical Genetics.... Mar 2018Recently, in a cohort study with "overgrowth syndrome with intellectual disability," five subjects were reported to have de novo heterozygous truncating variants in...
Recently, in a cohort study with "overgrowth syndrome with intellectual disability," five subjects were reported to have de novo heterozygous truncating variants in HIST1H1E, which encodes linker histone H 1.4. However, their growth pattern appeared complex that four out of five patients had a decreasing height percentile over time, and three of these patients began with above-average heights but exhibited reductions to average heights or below when they were older. Herein, we report a female patient with intellectual disability and distinctive facial features including a wide nasal bridge and prominent cheek bones. She did not exhibit skeletal overgrowth, but she had a short stature at 21 years of age. An exome analysis identified a de novo heterozygous 1-bp duplication in HIST1H1E, that is, c.433dup p.(Ala145Glyfs*51). The physical features of the proposita were essentially the same as those observed in patients with the aforementioned HIST1H1E-related overgrowth syndrome. Our review of the growth trajectories in seven patients showed that five of seven patients did not exhibit skeletal overgrowth. This "lack of overgrowth in overgrowth syndrome" is reminiscent of a subset of patients with a short stature who have Sotos syndrome, a prototypic overgrowth syndrome. Considering this complexity in growth, this newly identified condition should be referred to as Rahman syndrome.
Topics: Amino Acid Substitution; Child, Preschool; Exons; Facies; Female; Growth Disorders; Histones; Humans; Intellectual Disability; Mutation; Phenotype; Syndrome
PubMed: 29383847
DOI: 10.1002/ajmg.a.38616 -
American Journal of Medical Genetics.... Aug 2021
Topics: Child; Disease Management; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Imatinib Mesylate; Male; Phenotype; Receptor, Platelet-Derived Growth Factor beta; Syndrome; Treatment Outcome
PubMed: 33979467
DOI: 10.1002/ajmg.a.62264 -
American Journal of Medical Genetics.... Jun 2019Overgrowth syndromes are rare genetic conditions which present as global or segmental hyperplasia and are sometimes associated with increased risk of malignancy. Trisomy...
Overgrowth syndromes are rare genetic conditions which present as global or segmental hyperplasia and are sometimes associated with increased risk of malignancy. Trisomy of the terminal portion of 15q which includes the IGFR1 gene, produces a rare overgrowth phenotype that has been termed 15q overgrowth syndrome (15q OGS). Upregulation of IGF1R has long been implicated in oncogenesis of multiple cancer types, including acute leukemias, and has been shown to render cells more susceptible to other transforming events. To date, too few cases of 15q OGS have been reported to identify any cancer predisposition. We present a case of a 34-year-old female with intellectual disability, macrocephaly, and subtle dysmorphic features who was diagnosed with mixed phenotype acute leukemia (lymphoid and myeloid). Prior to initiation of therapy she was referred to medical genetics for further evaluation and was identified as having a chromosomal translocation resulting in a partial trisomy of chromosome 15q, consistent with 15q OGS. A review of the literature for cases of malignancy in individuals with increased copy number of 15q revealed only one other reported patient. Given the small number of reported individuals, we cannot rule out an increased risk of cancer associated with this chromosomal overgrowth syndrome. Although concerns have been raised regarding treatment feasibility in the setting of chromosomal disorders, the reported patient underwent successful treatment with allogeneic hematopoietic stem-cell transplant.
Topics: Adult; Chromosomes, Human, Pair 15; Facies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Growth Disorders; Humans; Leukemia; Neoplasms; Pedigree; Receptor, IGF Type 1; Signal Transduction; Syndrome; Trisomy
PubMed: 30861314
DOI: 10.1002/ajmg.a.61115 -
Endocrinologia, Diabetes Y Nutricion 2020Obesity is a prevalent health problem in our population. Bariatric surgery is the indicated treatment for severe cases. It is very effective (together with an adequate... (Review)
Review
Obesity is a prevalent health problem in our population. Bariatric surgery is the indicated treatment for severe cases. It is very effective (together with an adequate lifestyle modification) but it is also associated with frequent adverse events. One of the most frequent and disturbing adverse event is diarrhea. Diarrhea after bariatric surgery may be secondary to multiple causes and the physiopathogenic mechanisms may depend on the type of surgery performed. The most frequent diarrhea mechanisms are dumping syndrome, vagotomy, short bowel syndrome, carbohydrate malabsorption, protein malabsorption, alterations of the microbiota, Clostridium difficile infection, bacterial overgrowth, bile salt malabsorption, pancreatic insufficiency, endocrinological disorders, addictive disorders, and other digestive disorders not necessarily related to surgery.
Topics: Algorithms; Bariatric Surgery; Diarrhea; Humans; Postoperative Complications; Syndrome
PubMed: 31843494
DOI: 10.1016/j.endinu.2019.09.013 -
Hormone Research 2004This paper describes the isolation of a novel human gene, NSD1, from the 5q35 breakpoint of t(5;8)(q35; q24.1) in a patient with Sotos syndrome, and NSD1 mutation... (Review)
Review
This paper describes the isolation of a novel human gene, NSD1, from the 5q35 breakpoint of t(5;8)(q35; q24.1) in a patient with Sotos syndrome, and NSD1 mutation analysis. Of 112 (95 Japanese and 17 non-Japanese) patients analyzed, 16 (14%) had a heterozygous NSD1 point mutation (10 protein truncation types and six missense types) and 50 (45%) a approximately 0.7-Mb microdeletion involving NSD1. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome, and NSD1 plays a role in growth and brain development in humans. Detailed clinical examinations provided a genotype-phenotype correlation in Sotos syndrome, i.e. in patients with deletions, overgrowth is less obvious and mental retardation is more severe than in those with point mutations, and major anomalies were exclusively seen in the former. The results also indicated that Sotos syndrome due to a deletion falls into a contiguous gene syndrome, while Sotos syndrome due to an NSD1 point mutation is a single gene defect, occasionally with an autosomal dominant mode of inheritance. The genomic structure around the deleted and flanking regions revealed the presence of two sets of low copy repeats through which the microdeletion in Sotos syndrome is mediated.
Topics: Brain; Genetic Predisposition to Disease; Genotype; Gigantism; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Nuclear Proteins; Phenotype; Sequence Deletion; Syndrome
PubMed: 15539801
DOI: 10.1159/000080501 -
Pediatric Radiology Dec 2022Overgrowth syndromes can manifest with enlargement of the brain and other body parts and are associated with malignancy. Much of the current literature focuses on the... (Review)
Review
Overgrowth syndromes can manifest with enlargement of the brain and other body parts and are associated with malignancy. Much of the current literature focuses on the imaging findings of the somatic overgrowth, while there is relatively little describing the overgrowth of the central nervous system. In this pictorial essay, we discuss common syndromes with central nervous system overgrowth, highlight key imaging features, and review the underlying genetics, including the PI3K-AKT-mTOR pathway as well as other syndromes from various genes.
Topics: Humans; Central Nervous System; Mutation; Neuroimaging; Phosphatidylinositol 3-Kinases; Syndrome
PubMed: 36207456
DOI: 10.1007/s00247-022-05408-5 -
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 -
American Journal of Medical Genetics.... Aug 2005Sotos syndrome is a genetic disorder characterized by a typical facial appearance, macrocephaly, accelerated growth, developmental delay, and a variable range of... (Review)
Review
Sotos syndrome is a genetic disorder characterized by a typical facial appearance, macrocephaly, accelerated growth, developmental delay, and a variable range of associated abnormalities. The NSD1 gene was recently found to be responsible for Sotos syndrome, and more than 150 patients with NSD1 alterations have been identified. A significant ethnic difference is found in the prevalence of different types of mutation, with a high percentage of microdeletions identified in Japanese Sotos syndrome patients and with intragenic mutations in most non-Japanese patients. NSD1 aberrations are rather specific for Sotos syndrome, but have also been detected in patients lacking one or more major criteria of the disorder, namely overgrowth, macrocephaly, and advanced bone age. Thus, new diagnostic criteria should be considered. Studies have reported different frequencies of mutations versus non-mutations in Sotos syndrome, thus indicating allelic or locus hetereogeneity. Although some authors have suggested genotype/phenotype correlations, further studies are needed.
Topics: Abnormalities, Multiple; Growth Disorders; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Humans; Intracellular Signaling Peptides and Proteins; Mutation; Neoplasms; Nuclear Proteins; Syndrome
PubMed: 16010675
DOI: 10.1002/ajmg.c.30061