Weaver Syndrome and EZH2-Related Overgrowth Syndromes

2019 ◽  
pp. 95-126 ◽  
Author(s):  
David D. Weaver
Keyword(s):  
Gene Product ◽  
Histone Modifications ◽  
Bone Age ◽  
Polycomb Repressive Complex ◽  
Causative Gene ◽  
Epigenetic Signal ◽  
Increased Risk ◽  
Weaver Syndrome ◽  
Related Proteins ◽  
Overgrowth Syndromes

Comprehensive details on Weaver syndrome, one of the best recognized of the overgrowth syndromes, are presented in this chapter. The syndrome is characterized by overgrowth of prenatal onset, a distinctive craniofacial appearance, camptodactyly, widened metaphysis, accelerated bone age, and developmental delay. Like other overgrowth syndromes, Weaver syndrome is accompanied by an increased risk of malignancies, neuroblastoma, leukemia, and lymphoma in particular. The diagnosis relied on clinical evaluation alone until 2012 when the causative gene, EZH2, was discovered. The gene product joins with other related proteins to form a polycomb repressive complex that functions as an epigenetic signal that compacts chromatin and silences genes by histone modifications.

Selection of Less-Prevalent Overgrowth Syndromes

2019 ◽  
pp. 19-38
Author(s):  
Roger E. Stevenson ◽  
Bryan D. Hall
Keyword(s):  
Case Report ◽  
Environmental Influences ◽  
Maternal Diabetes ◽  
Fetal Life ◽  
Genomic Alterations ◽  
Causative Gene ◽  
Increased Risk ◽  
Genomic Disorders ◽  
Overgrowth Syndromes ◽  
Selection Of

In addition to the major generalized overgrowth syndromes described in this text, there is a rich case report literature on less common and less well-defined disorders in which overgrowth has been noted. The latter disorders are described concisely in this chapter. In some cases there have been multiple cases reported and the causative gene or genomic alterations have been identified. Although others are suspected to be genetic or genomic disorders, no specific cause has been implicated. These disorders are sufficiently uncommon that a body of literature has not accumulated and the manifestations are sufficiently variable that most are not clinically recognized. In addition, the chapter takes note of those environmental influences that can produce overgrowth. Maternal diabetes is the most common of the environmental influences that cause overgrowth during fetal life and carries a several-fold increased risk of malformations.

scholarly journals The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping-Hsun Wu ◽  
Yi-Ting Lin ◽  
Yi-Wen Chiu ◽  
Gabriel Baldanzi ◽  
Jiun-Chi Huang ◽  
...  
Keyword(s):  
Hemodialysis Patients ◽  
Complement Component ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Free Form ◽  
Negatively Associated ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Related Proteins ◽  
The Relationship

AbstractProtein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

Proteus Syndrome

2019 ◽  
pp. 199-216 ◽  
Author(s):  
Leslie G. Biesecker
Keyword(s):  
Somatic Mosaicism ◽  
Body Part ◽  
The Body ◽  
National Institutes Of Health ◽  
Proteus Syndrome ◽  
Neoplastic Disease ◽  
Increased Risk ◽  
Activating Mutation ◽  
Segmental Overgrowth ◽  
Overgrowth Syndromes

Proteus syndrome is an exceedingly rare disorder, perhaps the least common of all overgrowth syndromes but one of the most distinctive because of its segmental nature and unrelenting progression. Proteus syndrome occurs sporadically and was the first of the segmental overgrowth syndromes found to be caused by somatic mosaicism. The discovery of an activating mutation in AKT1 by Les Biesecker and colleagues at the National Institutes of Health provided the initial molecular proof for somatic mosaicism in Proteus syndrome. Overgrowth in Proteus syndrome can involve nearly any tissue or part of the body. Presumably a germline mutation that would affect all tissues of the body would be lethal. Overgrowth of a tissue or a body part is the distinctive manifestation of Proteus syndrome but in most cases will be accompanied by other cutaneous, skeletal, vascular, or soft tissue findings. Although the possibility of an increased risk for developing neoplastic disease is a concern in any overgrowth disorder, this has not been demonstrated in Proteus syndrome.

Malan Syndrome

2019 ◽  
pp. 153-162
Author(s):  
Manuela Priolo ◽  
Martin Zenker ◽  
Raoul C. Hennekam
Keyword(s):  
Transcription Factor ◽  
Differential Diagnosis ◽  
Intellectual Disability ◽  
Bone Age ◽  
Nuclear Factor ◽  
Connective Tissues ◽  
Causative Gene ◽  
Molecular Abnormalities ◽  
Large Head ◽  
Visual Problems

The chapter discusses the clinical phenotype and the molecular abnormalities in Malan syndrome, an overgrowth condition caused by mutations in the NFIX gene. Overgrowth in Malan syndrome can be present at birth, especially in terms of large head circumference, and it continues after birth, although statural growth velocity decreases with age. The syndrome is also characterized by dysmorphic facial traits, skeletal abnormalities, intellectual disability, visual problems, and advanced bone age. This condition is allelic to another overgrowth disorder, Marshall-Smith syndrome, with which it shares several clinical features and should be considered in the differential diagnosis. The causative gene for both conditions, NFIX, encodes the nuclear factor one X-type transcription factor, which regulates the growth of several types of connective tissues.

Current Concepts in Tall Stature and Overgrowth Syndromes

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
S.L.S. Drop ◽  
N. Greggio ◽  
M. Cappa ◽  
S. Bernasconi
Keyword(s):  
Sex Steroids ◽  
Bone Age ◽  
Prediction Equation ◽  
Favourable Effect ◽  
Tall Stature ◽  
Growth Data ◽  
Therapeutic Modalities ◽  
Height Prediction ◽  
High Doses ◽  
Overgrowth Syndromes

AbstractIn this overview an update is given on the pathogenesis, classification and differential diagnosis of overgrowth syndromes. In addition, height prognosis and therapeutic modalities available for managing mainly constitutional tall stature are discussed. Constitutional tall stature comprises normal variants in which one or both parents are tall. Primary disorders may have a prenatal onset and may be of chromosomal or genetic origin. Secondary overgrowth syndromes are most often the result of hormonal disturbances. Height prediction plays a key role in the management of tall children. Prediction equation models have been developed based on the growth data of healthy tall children. There is general agreement that a favourable effect on reducing ultimate height is obtained using high doses of sex steroids (girls 100-300 μg ethinyl- oestradiol; boys testosterone (T) ester depot preparations 250-1000 mg/month), the height reduction being greater when the treatment is started at a lower chronological and/or bone age. An alternative is the induction of puberty with low doses of sex steroids (girls 5-50 μg ethinyloestradiol; boys T esters 25-50 mg/m

scholarly journals A subunit of the dynein regulatory complex in Chlamydomonas is a homologue of a growth arrest–specific gene product

2003 ◽  
Vol 162 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Gerald Rupp ◽  
Mary E. Porter
Keyword(s):  
Gene Product ◽  
Insertional Mutagenesis ◽  
Growth Arrest ◽  
Coiled Coil ◽  
Specific Gene ◽  
Flagellar Motility ◽  
Wide Range ◽  
Motility Mutant ◽  
Regulatory Complex ◽  
Related Proteins

The dynein regulatory complex (DRC) is an important intermediate in the pathway that regulates flagellar motility. To identify subunits of the DRC, we characterized a Chlamydomonas motility mutant obtained by insertional mutagenesis. The pf2-4 mutant displays an altered waveform that results in slow swimming cells. EM analysis reveals defects in DRC structure that can be rescued by reintroduction of the wild-type PF2 gene. Immunolocalization studies show that the PF2 protein is distributed along the length of the axoneme, where it is part of a discrete complex of polypeptides. PF2 is a coiled-coil protein that shares significant homology with a mammalian growth arrest–specific gene product (Gas11/Gas8) and a trypanosome protein known as trypanin. PF2 and its homologues appear to be universal components of motile axonemes that are required for DRC assembly and the regulation of flagellar motility. The expression of Gas8/Gas11 transcripts in a wide range of tissues may also indicate a potential role for PF2-related proteins in other microtubule-based structures.

scholarly journals Effects of High and Low Sodium Diet on Blood Pressure and Heart Rate in Mice Lacking the Functional Grainyhead-Like 1 Gene

2017 ◽  
pp. 163-165 ◽  
Author(s):  
A. WALKOWSKA ◽  
M. PAWLAK ◽  
S. M. JANE ◽  
E. KOMPANOWSKA-JEZIERSKA ◽  
T. WILANOWSKI
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Standard Diet ◽  
Wild Type ◽  
Causative Gene ◽  
Major Health Problem ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Increased Risk

Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular disease. Two independent studies discovered a locus conferring susceptibility to essential hypertension on chromosome 2, in the 2p25 region, but the causative gene remains unknown. Grainyhead-like 1 (GRHL1) is one of the genes located in this region. Our experiments determined that the Grhl1-null mice, when fed standard diet, have the same blood pressure as their wild type littermate controls. However, we discovered that blood pressure of these mice increases following high sodium diet and decreases when they are fed low sodium diet, and similar effects were not observed in the control wild type littermates. This suggests that the Grhl1-null mice are sensitive to the development of salt-sensitive hypertension. Thus it is possible that the GRHL1 gene is involved in the regulation of blood pressure, and it may be the causative gene for the locus of susceptibility to essential hypertension in the 2p25 region.

scholarly journals Overgrowth Syndromes—Evaluation, Diagnosis, and Management

2020 ◽  
Vol 8 ◽  
Author(s):  
Joshua Manor ◽  
Seema R. Lalani
Keyword(s):  
Molecular Mechanisms ◽  
Human Growth ◽  
Medical Complications ◽  
Complex Interplay ◽  
Hormonal Factors ◽  
Health Concerns ◽  
Diagnosis And Management ◽  
Increased Risk ◽  
Prompt Diagnosis ◽  
Overgrowth Syndromes

Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth syndromes generally present with inherent health concerns and, in some instances, an increased risk of tumor predisposition that necessitate prompt diagnosis and appropriate referral. In this review, we introduce some of the more common overgrowth syndromes, along with their molecular mechanisms, diagnostics, and medical complications for improved recognition and management of patients affected with these disorders.

Reductive Otoplasty and Facial Debulking in a Pediatric Patient With PIK3CA-Related Overgrowth

FACE ◽  
2021 ◽  
pp. 273250162110482
Author(s):  
Rishub K. Das ◽  
Barry G. Rahman ◽  
James D. Phillips ◽  
Alexandra J. Borst ◽  
Nolan Jaeger ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Vascular Malformations ◽  
Genetic Diseases ◽  
Facial Soft Tissue ◽  
Novel Approach ◽  
Rare Genetic Diseases ◽  
Increased Risk ◽  
Surgical Debulking ◽  
Segmental Overgrowth ◽  
Overgrowth Syndromes

Overgrowth syndromes encompass a number of rare genetic diseases with heterogeneous clinical phenotypes. Accordingly, there is a strong imperative to collect data and classify these disorders to aid in diagnosis and management. Recent advances in the genetics of overgrowth syndromes have identified mutations in the PIK3CA gene. These somatic mutations manifest in progressive segmental overgrowth of fibrous and adipose tissue and bone, vascular malformations, and in some cases, increased risk for malignancy. Targeted medical therapy is under investigation for the management of PROS, but treatment of overgrowth relies on surgical debulking. Macrotia in PIK3CA-related overgrowth spectrum (PROS) has not been reported in the literature. In this case, we discuss a novel approach to reductive otoplasty and facial soft tissue debulking in a pediatric patient with PROS.

Sign in / Sign up

Export Citation Format

Share Document