Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0003
A. Mussa, J. Kalish, F. Cerrato, A. Riccio, G. Ferrero
This chapter provides a thorough overview of Beckwith-Wiedemann syndrome, which is considered to be the most common of the overgrowth syndromes and imprinting disorders. It starts with a description of the clinical aspects of the condition, including diagnostic criteria, differential diagnosis, risk of malignancy, and management. This is followed by an in-depth description of the genetic causes of the syndrome and of the molecular pathways involved in the pathogenesis of this disorder. The complexities of the etiology, which involves two neighboring loci, each one regulated by finely tuned imprinting mechanisms, are clearly delineated. The chapter also touches on the reported association between in vitro fertilization and risk of conceiving a baby with this syndrome.
{"title":"Beckwith-Wiedemann Syndrome","authors":"A. Mussa, J. Kalish, F. Cerrato, A. Riccio, G. Ferrero","doi":"10.1093/med/9780190944896.003.0003","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0003","url":null,"abstract":"This chapter provides a thorough overview of Beckwith-Wiedemann syndrome, which is considered to be the most common of the overgrowth syndromes and imprinting disorders. It starts with a description of the clinical aspects of the condition, including diagnostic criteria, differential diagnosis, risk of malignancy, and management. This is followed by an in-depth description of the genetic causes of the syndrome and of the molecular pathways involved in the pathogenesis of this disorder. The complexities of the etiology, which involves two neighboring loci, each one regulated by finely tuned imprinting mechanisms, are clearly delineated. The chapter also touches on the reported association between in vitro fertilization and risk of conceiving a baby with this syndrome.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120990945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/MED/9780190944896.003.0009
Lamis Yehia, J. Ngeow, C. Eng
Individuals carrying germline mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN) may present with diverse clinical phenotypes, grouped under the term of PTEN hamartoma tumor syndrome (PHTS). This chapter will focus on two PHTS conditions: Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome. The first condition is an autosomal dominant disorder characterized by macrocephaly, intestinal hamartomatous polyposis, vascular malformations, lipomas, hemangiomas, and genital freckling. Other features include developmental delay, hypotonia, and scoliosis. Cowden syndrome is also an autosomal dominant disorder, mainly characterized by multiple hamartomas and high risk of breast, thyroid, and other cancers. PTEN encodes the main inhibitor of the PI3K-AKT pathway, regulating cell growth and proliferation, and protein synthesis. Therefore, germline loss-of-function mutations in this gene lead to excessive growth, particularly affecting connective tissues. Detection of PTEN mutations is critical for clinical management and treatment strategies.
{"title":"PTEN-Related Overgrowth Syndromes","authors":"Lamis Yehia, J. Ngeow, C. Eng","doi":"10.1093/MED/9780190944896.003.0009","DOIUrl":"https://doi.org/10.1093/MED/9780190944896.003.0009","url":null,"abstract":"Individuals carrying germline mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN) may present with diverse clinical phenotypes, grouped under the term of PTEN hamartoma tumor syndrome (PHTS). This chapter will focus on two PHTS conditions: Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome. The first condition is an autosomal dominant disorder characterized by macrocephaly, intestinal hamartomatous polyposis, vascular malformations, lipomas, hemangiomas, and genital freckling. Other features include developmental delay, hypotonia, and scoliosis. Cowden syndrome is also an autosomal dominant disorder, mainly characterized by multiple hamartomas and high risk of breast, thyroid, and other cancers. PTEN encodes the main inhibitor of the PI3K-AKT pathway, regulating cell growth and proliferation, and protein synthesis. Therefore, germline loss-of-function mutations in this gene lead to excessive growth, particularly affecting connective tissues. Detection of PTEN mutations is critical for clinical management and treatment strategies.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130208557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/MED/9780190944896.003.0012
K. Keppler-Noreuil
Postzygotic mutations of the PIK3CA gene are associated with a series of clinical phenotypes characterized by segmental overgrowth and recently grouped under the term PIK3CA-related overgrowth spectrum (PROS). This chapter provides an overview of the clinical features shared by the phenotypes in PROS, including both the conditions with isolated features and the ones with syndromal presentation. The somatic overgrowth in cases with PROS is asymmetric, progressive, and “ballooning” in appearance and tends to involve predominantly the limbs, including fingers and toes, although the trunk and face are often affected as well. The tissues affected in the overgrowth can include all or some of these types: fibrous, adipose, vascular, nervous, and skeletal. Somatic gain-of-function mutations of PIK3CA cause activation of the PI3K-AKT pathway, leading to excessive cell growth and proliferation. Timing of PIK3CA mutations, tissue specificity, and type of mutation may play a role in the phenotypic variability of PROS.
{"title":"PIK3CA-Related Overgrowth Spectrum","authors":"K. Keppler-Noreuil","doi":"10.1093/MED/9780190944896.003.0012","DOIUrl":"https://doi.org/10.1093/MED/9780190944896.003.0012","url":null,"abstract":"Postzygotic mutations of the PIK3CA gene are associated with a series of clinical phenotypes characterized by segmental overgrowth and recently grouped under the term PIK3CA-related overgrowth spectrum (PROS). This chapter provides an overview of the clinical features shared by the phenotypes in PROS, including both the conditions with isolated features and the ones with syndromal presentation. The somatic overgrowth in cases with PROS is asymmetric, progressive, and “ballooning” in appearance and tends to involve predominantly the limbs, including fingers and toes, although the trunk and face are often affected as well. The tissues affected in the overgrowth can include all or some of these types: fibrous, adipose, vascular, nervous, and skeletal. Somatic gain-of-function mutations of PIK3CA cause activation of the PI3K-AKT pathway, leading to excessive cell growth and proliferation. Timing of PIK3CA mutations, tissue specificity, and type of mutation may play a role in the phenotypic variability of PROS.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129234879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0010
J. Kalish, G. Ferrero, A. Mussa
The chapter discusses body asymmetry occurring as an isolated clinical feature or as part of well-characterized syndromes. The term “lateralized overgrowth” has been recently introduced to describe conditions characterized by disproportionate growth of one side of the body that might be caused by hemihyperplasia and/or hemihypertrophy. The chapter also provides a brief clinical overview of the major syndromes associated with lateralized overgrowth and discusses the molecular anomalies causing this disorder. Prognosis of conditions characterized by lateralized overgrowth varies according to the underlying cause. Treatment and management of conditions characterized by lateralized overgrowth mainly focus on tumor surveillance and management of eventual difference of limb length. Leg-length discrepancy can be associated with significant morbidity and can negatively influence the quality of life.
{"title":"Lateralized Overgrowth","authors":"J. Kalish, G. Ferrero, A. Mussa","doi":"10.1093/med/9780190944896.003.0010","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0010","url":null,"abstract":"The chapter discusses body asymmetry occurring as an isolated clinical feature or as part of well-characterized syndromes. The term “lateralized overgrowth” has been recently introduced to describe conditions characterized by disproportionate growth of one side of the body that might be caused by hemihyperplasia and/or hemihypertrophy. The chapter also provides a brief clinical overview of the major syndromes associated with lateralized overgrowth and discusses the molecular anomalies causing this disorder. Prognosis of conditions characterized by lateralized overgrowth varies according to the underlying cause. Treatment and management of conditions characterized by lateralized overgrowth mainly focus on tumor surveillance and management of eventual difference of limb length. Leg-length discrepancy can be associated with significant morbidity and can negatively influence the quality of life.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116768584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0008
M. Priolo, M. Zenker, R. Hennekam
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.
{"title":"Malan Syndrome","authors":"M. Priolo, M. Zenker, R. Hennekam","doi":"10.1093/med/9780190944896.003.0008","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0008","url":null,"abstract":"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.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130678563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/MED/9780190944896.003.0002
R. Stevenson, B. Hall
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.
{"title":"Selection of Less-Prevalent Overgrowth Syndromes","authors":"R. Stevenson, B. Hall","doi":"10.1093/MED/9780190944896.003.0002","DOIUrl":"https://doi.org/10.1093/MED/9780190944896.003.0002","url":null,"abstract":"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.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117005277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0005
D. Weaver
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.
{"title":"Weaver Syndrome and EZH2-Related Overgrowth Syndromes","authors":"D. Weaver","doi":"10.1093/med/9780190944896.003.0005","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0005","url":null,"abstract":"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.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124045237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0004
P. Lapunzina, J. Tenorio
This chapter describes Sotos syndrome as a clinical entity characterized, in addition to overgrowth, by distinctive craniofacial manifestations that include macrocephaly, a tall forehead, and an elongated face with pointed chin. This clinical aspect is illustrated by photographs of patients. The differential diagnosis between Sotos and other overgrowth syndromes can be particularly difficult and is therefore described in detail, with the aid of a summary table. The genetic cause and inherent pathogenic mechanisms are clearly delineated. Even though malignancies are reported in less than 1% of patients with Sotos syndrome, this potential risk is not to be disregarded and is the object of a thorough discussion.
{"title":"Sotos Syndrome","authors":"P. Lapunzina, J. Tenorio","doi":"10.1093/med/9780190944896.003.0004","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0004","url":null,"abstract":"This chapter describes Sotos syndrome as a clinical entity characterized, in addition to overgrowth, by distinctive craniofacial manifestations that include macrocephaly, a tall forehead, and an elongated face with pointed chin. This clinical aspect is illustrated by photographs of patients. The differential diagnosis between Sotos and other overgrowth syndromes can be particularly difficult and is therefore described in detail, with the aid of a summary table. The genetic cause and inherent pathogenic mechanisms are clearly delineated. Even though malignancies are reported in less than 1% of patients with Sotos syndrome, this potential risk is not to be disregarded and is the object of a thorough discussion.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117248437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-01DOI: 10.1093/med/9780190944896.003.0006
G. Neri
Simpson-Golabi-Behmel syndrome was described independently by three groups of authors and eventually received its current designation by the author of this chapter. Among all the conditions described in this book, it is the only one to have X-linked inheritance, with possible expression in some carrier females. Therefore, the description of the clinical phenotype is subdivided into two parts, one pertaining to males, the other to females. Typically present in both affected males and females is a “coarseness” of the facial traits, in addition to a number of congenital malformations that can affect the heart, the diaphragm, and the skeleton. Differential diagnosis and recurrence risks are clearly delineated. The genetic cause is described in detail and the pathogenic mechanism is illustrated by an explanatory cartoon.
{"title":"Simpson-Golabi-Behmel Syndrome","authors":"G. Neri","doi":"10.1093/med/9780190944896.003.0006","DOIUrl":"https://doi.org/10.1093/med/9780190944896.003.0006","url":null,"abstract":"Simpson-Golabi-Behmel syndrome was described independently by three groups of authors and eventually received its current designation by the author of this chapter. Among all the conditions described in this book, it is the only one to have X-linked inheritance, with possible expression in some carrier females. Therefore, the description of the clinical phenotype is subdivided into two parts, one pertaining to males, the other to females. Typically present in both affected males and females is a “coarseness” of the facial traits, in addition to a number of congenital malformations that can affect the heart, the diaphragm, and the skeleton. Differential diagnosis and recurrence risks are clearly delineated. The genetic cause is described in detail and the pathogenic mechanism is illustrated by an explanatory cartoon.","PeriodicalId":210886,"journal":{"name":"Overgrowth Syndromes","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125409398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：