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The Journal of Clinical Endocrinology... May 2022Pseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1....
Pseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1. Acromegaloid physical features or accelerated growth in a patient may prompt referral to endocrinologists. Because pseudoacromegaly conditions are rare and heterogeneous, often with overlapping clinical features, the underlying diagnosis may be challenging to establish. As many of these have a genetic origin, such as pachydermoperiostosis, Sotos syndrome, Weaver syndrome, or Cantú syndrome, collaboration is key with clinical geneticists in the diagnosis of these patients. Although rare, awareness of these uncommon conditions and their characteristic features will help their timely recognition.
Topics: Acromegaly; Gigantism; Humans; Hypertrichosis; Insulin Resistance; Osteochondrodysplasias
PubMed: 34792134
DOI: 10.1210/clinem/dgab789 -
American Journal of Medical Genetics Mar 2001We report on an infant with Weaver syndrome, neoplasia and cardiovascular anomalies. Stage 4S neuroblastoma underwent spontaneous resolution. Three neoplasms have been...
We report on an infant with Weaver syndrome, neoplasia and cardiovascular anomalies. Stage 4S neuroblastoma underwent spontaneous resolution. Three neoplasms have been reported in Weaver syndrome: another stage 4S neuroblastoma [Muhonen and Menezes, 1990: J Pediatr 116:596-599], an ovarian endodermal sinus tumor [Derry et al., 1999: J Med Genet 36:725-728], and a sacrococcygeal teratoma [Kelly et al., 2000: Am J Med Genet 95:492-495]. No case was associated with cardiovascular anomalies. Our patient had VSD and PDA, and although several other patients with Weaver syndrome have had cardiovascular anomalies, they were shown not to have neoplasia.
Topics: Abnormalities, Multiple; Heart Defects, Congenital; Humans; Infant, Newborn; Liver Neoplasms; Male; Neoplasm Staging; Neuroblastoma; Syndrome
PubMed: 11241499
DOI: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1169>3.0.co;2-l -
Indian Journal of Human Genetics Jan 2009
PubMed: 20407649
DOI: 10.4103/0971-6866.50869 -
American Journal of Medical Genetics May 1989We report on a 25-year-old woman who was diagnosed with Weaver syndrome after reevaluation because of the family's concern regarding recurrence risk for mental...
We report on a 25-year-old woman who was diagnosed with Weaver syndrome after reevaluation because of the family's concern regarding recurrence risk for mental retardation in offspring of the woman's brother. The diagnosis was suggested on the basis of postnatal growth excess, camptodactyly, and developmental delay, but with a somewhat atypical facial appearance. When childhood photographs were reviewed, her facial characteristics were more consistent with those of Weaver syndrome in early childhood, but became less obvious with age. This is the second adult reported with Weaver syndrome and provides documentation of the adult phenotype. The diagnosis may be more difficult to make in adolescents and adults if one uses criteria developed for facial manifestations in young children.
Topics: Adult; Facial Expression; Female; Fingers; Genes, Recessive; Growth Disorders; Humans; Intellectual Disability; Syndrome
PubMed: 2750780
DOI: 10.1002/ajmg.1320330120 -
Current Opinion in Structural Biology Apr 2021The polycomb repressive complex 2 (PRC2) is a conserved multiprotein, repressive chromatin complex essential for development and maintenance of eukaryotic cellular... (Review)
Review
The polycomb repressive complex 2 (PRC2) is a conserved multiprotein, repressive chromatin complex essential for development and maintenance of eukaryotic cellular identity. PRC2 comprises a trimeric core of SUZ12, EED and EZH1/2, which together with RBBP4/7 is sufficient to catalyse mono-methylation, di-methylation and tri-methylation of histone H3 at lysine 27 (H3K27me1/2/3). These histone methyltransferase activities of PRC2 are deregulated in several human cancers and certain developmental disorders, such as Weaver Syndrome. Core PRC2 associates with several accessory proteins, which organise to define two main subassemblies, PRC2.1 and PRC2.2. Here we review new biochemical and structural studies that are providing critical insights into how core and accessory PRC2 subunits coordinate the faithful deposition of H3K27 methylations genome-wide.
Topics: Chromatin; Histones; Humans; Methylation; Polycomb Repressive Complex 2; Protein Processing, Post-Translational
PubMed: 33232890
DOI: 10.1016/j.sbi.2020.10.017 -
American Journal of Medical Genetics.... Jul 2021
Topics: Abnormalities, Multiple; Adolescent; Child; Congenital Hypothyroidism; Craniofacial Abnormalities; Enhancer of Zeste Homolog 2 Protein; Fingers; Hand Deformities, Congenital; Humans; Male; Polydactyly; Toes
PubMed: 33788986
DOI: 10.1002/ajmg.a.62189 -
American Journal of Human Genetics Jan 2003Sotos syndrome is a childhood overgrowth syndrome characterized by a distinctive facial appearance, height and head circumference >97th percentile, advanced bone age,...
Sotos syndrome is a childhood overgrowth syndrome characterized by a distinctive facial appearance, height and head circumference >97th percentile, advanced bone age, and developmental delay. Weaver syndrome is characterized by the same criteria but has its own distinctive facial gestalt. Recently, a 2.2-Mb chromosome 5q35 microdeletion, encompassing NSD1, was reported as the major cause of Sotos syndrome, with intragenic NSD1 mutations identified in a minority of cases. We evaluated 75 patients with childhood overgrowth, for intragenic mutations and large deletions of NSD1. The series was phenotypically scored into four groups, prior to the molecular analyses: the phenotype in group 1 (n=37) was typical of Sotos syndrome; the phenotype in group 2 (n=13) was Sotos-like but with some atypical features; patients in group 3 (n=7) had Weaver syndrome, and patients in group 4 (n=18) had an overgrowth condition that was neither Sotos nor Weaver syndrome. We detected three deletions and 32 mutations (13 frameshift, 8 nonsense, 2 splice-site, and 9 missense) that are likely to impair NSD1 functions. The truncating mutations were spread throughout NSD1, but there was evidence of clustering of missense mutations in highly conserved functional domains between exons 13 and 23. There was a strong correlation between presence of an NSD1 alteration and clinical phenotype, in that 28 of 37 (76%) patients in group 1 had NSD1 mutations or deletions, whereas none of the patients in group 4 had abnormalities of NSD1. Three patients with Weaver syndrome had NSD1 mutations, all between amino acids 2142 and 2184. We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes.
Topics: Abnormalities, Multiple; Amino Acid Sequence; Carrier Proteins; Child; Chromosome Deletion; Chromosomes, Human, Pair 5; Craniofacial Abnormalities; DNA Mutational Analysis; Developmental Disabilities; Exons; Female; Growth Disorders; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Humans; Intracellular Signaling Peptides and Proteins; Introns; Male; Molecular Sequence Data; Mutation; Nuclear Proteins; Pedigree; Phenotype; Polymorphism, Genetic; Protein Structure, Tertiary; Sequence Deletion; Syndrome
PubMed: 12464997
DOI: 10.1086/345647 -
Special Care in Dentistry : Official... Sep 2015Weaver syndrome is a rare condition characterized by accelerated growth, advanced osseous maturation, and distinct craniofacial features that can occur in both males and...
Weaver syndrome is a rare condition characterized by accelerated growth, advanced osseous maturation, and distinct craniofacial features that can occur in both males and females. Etiology is unknown and no definitive oral characteristics have been established. The objective of this case report is to describe the oral and radiographic findings of a 14-year-old male with Weaver syndrome. A comprehensive dental examination was performed under general anesthesia. The clinical findings were: severe generalized heavy plaque with subgingival calculus, gingival edema, malocclusion and maxillary atresia, mild micrognathia of the mandible, enlarged tongue, and bifid uvula. Clinical and radiographic caries were not found. Out of over 40 possible cases of Weaver syndrome previously reported in the literature, only two were related to the oral cavity. Bifida uvula was not mentioned until now as clinical findings associated with the syndrome. Autism, macroglossia, and cleft palate were seldom mentioned. The oral manifestations in Weaver syndrome are not yet well known. Future studies will be required to improve the subject matter.
PubMed: 26084782
DOI: 10.1111/scd.12122 -
The Journal of Pediatrics Feb 1986Seven new cases of Weaver syndrome are described, including the first reported case in an adult. Overgrowth is usually but not always present. The combination of... (Comparative Study)
Comparative Study
Seven new cases of Weaver syndrome are described, including the first reported case in an adult. Overgrowth is usually but not always present. The combination of characteristic facies and developmental delay, with the peculiar radiographic findings of accelerated dysharmonic osseous maturation and splaying of the distal long bones, is diagnostic of Weaver syndrome.
Topics: Adult; Bone Development; Child; Child, Preschool; Developmental Disabilities; Facial Expression; Female; Growth Disorders; Humans; Infant; Male; Radiography; Syndrome
PubMed: 2418189
DOI: 10.1016/s0022-3476(86)80988-x -
American Journal of Medical Genetics.... Jan 2013
Topics: Abnormalities, Multiple; Congenital Hypothyroidism; Craniofacial Abnormalities; Enhancer of Zeste Homolog 2 Protein; Exons; Hand Deformities, Congenital; Humans; Infant; Male; Mutation; Polycomb Repressive Complex 2
PubMed: 23239504
DOI: 10.1002/ajmg.a.35660