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Operative Neurosurgery (Hagerstown, Md.) Aug 2021
Commentary: Posteromedial Hypothalamic Deep Brain Stimulation for Refractory Aggressiveness in a Patient With Weaver Syndrome: Clinical, Technical Report and Operative Video.
Topics: Abnormalities, Multiple; Congenital Hypothyroidism; Craniofacial Abnormalities; Deep Brain Stimulation; Hand Deformities, Congenital; Humans
PubMed: 34038954
DOI: 10.1093/ons/opab165 -
Journal of Medical Genetics Jun 1980Several investigators have suggested that the Marshall syndrome and the Weaver syndrome are one entity because of some phenotypic overlap. This paper reviews the...
Several investigators have suggested that the Marshall syndrome and the Weaver syndrome are one entity because of some phenotypic overlap. This paper reviews the findings in nine additional patients with the Marshall syndrome and concludes that the syndromes are two distinct entities. In the Marshall syndrome there is a characteristic facies, failure to thrive in terms of height, weight, and psychomotor development, and early death. In the Weaver syndome the infants thrive too well: weight and heights are much above normal. They also have increased bifrontal diameters, hypertonia, prominent finger pads, and thin, deep-set nails, and the face is quite different from the Marshall facies.
Topics: Bone Diseases, Developmental; Child, Preschool; Diagnosis, Differential; Female; Growth Disorders; Humans; Infant; Male; Phenotype; Syndrome
PubMed: 7401127
DOI: 10.1136/jmg.17.3.174 -
The Journal of Pediatrics Apr 1990
Topics: Bone Diseases, Developmental; Cervical Vertebrae; Child, Preschool; Face; Female; Growth Disorders; Humans; Skull; Spinal Cord Compression; Spinal Diseases; Syndrome
PubMed: 2319408
DOI: 10.1016/s0022-3476(05)81611-7 -
Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome.Journal of Medical Genetics Apr 1998The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother...
The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms in the two cases were similar to the features reported in Weaver syndrome. Although the combination of NF1 and an overgrowth syndrome resembling Weaver syndrome in this family may be fortuitous, we favour the hypothesis that the deletion of the entire gene has caused this combined phenotype. Possible pathogenetic mechanisms are discussed. The observation suggests a relation between NF1 with an extraordinarily large gene deletion and a Weaver(-like) syndrome. This warrants investigation for deletions in the 17q11.2 region in Weaver(-like) syndrome patients.
Topics: Abnormalities, Multiple; Adult; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 17; Female; Genetic Diseases, Inborn; Growth Disorders; Humans; Male; Neurofibromatosis 1; Syndrome
PubMed: 9598729
DOI: 10.1136/jmg.35.4.323 -
Oncotarget Dec 2011The biological processes controlling human growth are diverse, complex and poorly understood. Genetic factors are important and human height has been shown to be a...
The biological processes controlling human growth are diverse, complex and poorly understood. Genetic factors are important and human height has been shown to be a highly polygenic trait to which common and rare genetic variation contributes. Weaver syndrome is a human overgrowth condition characterised by tall stature, dysmorphic facial features, learning disability and variable additional features. We performed exome sequencing in four individuals with Weaver syndrome, identifying a mutation in the histone methyltransferase, EZH2, in each case. Sequencing of EZH2 in additional individuals with overgrowth identified a further 15 mutations. The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies. Our data establish EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.
Topics: Abnormalities, Multiple; Amino Acid Sequence; Body Height; Congenital Hypothyroidism; Craniofacial Abnormalities; DNA-Binding Proteins; Enhancer of Zeste Homolog 2 Protein; Facies; Female; Germ-Line Mutation; Growth Disorders; Hand Deformities, Congenital; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Histones; Humans; Male; Polycomb Repressive Complex 2; Sequence Analysis, DNA; Transcription Factors
PubMed: 22190405
DOI: 10.18632/oncotarget.385 -
PM & R : the Journal of Injury,... Mar 2024
PubMed: 38529795
DOI: 10.1002/pmrj.13162 -
Human Mutation Jun 2017Weaver syndrome (WS) is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm...
Weaver syndrome (WS) is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected WS by whole-exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c.707G>C, p.Arg236Thr) in EED (individual 2), and a missense mutation (c.1829A>T, p.Glu610Val) in SUZ12 (suppressor of zeste 12 homolog) (individual 3) inherited from her father (individual 4) with a mosaic mutation. SUZ12 is another component of PRC2 and germline mutations in SUZ12 have not been previously reported in humans. In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased trimethylation of lysine 27 of histone H3. These data indicate that loss-of-function mutations of PRC2 components are an important cause of WS.
Topics: Abnormalities, Multiple; Adult; Child; Child, Preschool; Congenital Hypothyroidism; Craniofacial Abnormalities; Cullin Proteins; DNA-Binding Proteins; Enhancer of Zeste Homolog 2 Protein; Female; Hand Deformities, Congenital; Heterozygote; Histones; Humans; Male; Methylation; Mutation; Neoplasm Proteins; Pedigree; Polycomb Repressive Complex 2; Protein Interaction Maps; Transcription Factors
PubMed: 28229514
DOI: 10.1002/humu.23200 -
Current Opinion in Pediatrics Aug 2012Human growth ensues from a complex interplay of physiological factors, in the wider setting of varying genetic traits and environmental influences. Intensive research in... (Review)
Review
PURPOSE OF REVIEW
Human growth ensues from a complex interplay of physiological factors, in the wider setting of varying genetic traits and environmental influences. Intensive research in these divergent areas, and particularly in the field of genetics, continues to clarify the molecular basis of disorders which result in overgrowth, and it is therefore timely to provide a review of these findings.
RECENT FINDINGS
This article provides an overview of the factors which regulate growth, followed by a discussion of the more commonly encountered overgrowth syndromes and their genetic basis as it is understood at the current time. There is also an added focus on recently discovered genetic associations in some conditions, such as Weaver, Perlman and Proteus syndromes.
SUMMARY
New discoveries continue to be made regarding the genetic basis for many overgrowth syndromes and the development of a much needed molecular classification system for overgrowth may become possible as the interlinking functions of these genes on growth are unravelled. As there exists a wide spectrum of syndromes, disorders resulting in overgrowth can represent a diagnostic and therapeutic challenge, from those causing prenatal overgrowth with a poor prognosis to less severe genetic aberrations which are identified in later childhood or adult life.
Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Congenital Hypothyroidism; Craniofacial Abnormalities; Female; Fetal Macrosomia; Growth Disorders; Hand Deformities, Congenital; Humans; Infant; Male; Mutation; Phenotype; Prognosis; Proteus Syndrome; Wilms Tumor
PubMed: 22705997
DOI: 10.1097/MOP.0b013e3283558995 -
PloS One 2013Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) is a recessive neurological disease that has been observed in the Brown Swiss cattle breed since...
Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) is a recessive neurological disease that has been observed in the Brown Swiss cattle breed since the 1970's in North America and Europe. Bilateral hind leg weakness and ataxia appear in afflicted animals at 6 to 18 months of age, and slowly progresses to total loss of hind limb control by 3 to 4 years of age. While Weaver has previously been mapped to Bos taurus autosome (BTA) 4∶46-56 Mb and a diagnostic test based on the 6 microsatellite (MS) markers is commercially available, neither the causative gene nor mutation has been identified; therefore misdiagnosis can occur due to recombination between the diagnostic MS markers and the causative mutation. Analysis of 34,980 BTA 4 SNPs genotypes derived from the Illumina BovineHD assay for 20 Brown Swiss Weaver carriers and 49 homozygous normal bulls refined the Weaver locus to 48-53 Mb. Genotyping of 153 SNPs, identified from whole genome sequencing of 10 normal and 10 carrier animals, across a validation set of 841 animals resulted in the identification of 41 diagnostic SNPs that were concordant with the disease. Except for one intergenic SNP all are associated with genes expressed in nervous tissues: 37 distal to NRCAM, one non-synonymous (serine to asparagine) in PNPLA8, one synonymous and one non-synonymous (lysine to glutamic acid) in CTTNBP2. Haplotype and imputation analyses of 7,458 Brown Swiss animals with Illumina BovineSNP50 data and the 41 diagnostic SNPs resulted in the identification of only one haplotype concordant with the Weaver phenotype. Use of this haplotype and the diagnostic SNPs more accurately identifies Weaver carriers in both Brown Swiss purebred and influenced herds.
Topics: Amyotrophic Lateral Sclerosis; Animals; Base Sequence; Cattle; Cattle Diseases; Cell Adhesion Molecules; Central Nervous System Diseases; Chromosome Mapping; Genes, Recessive; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Lipase; Molecular Sequence Data; Myelin Sheath; Nerve Tissue Proteins; Neurodegenerative Diseases; Phenotype; Polymorphism, Single Nucleotide; Sequence Alignment; Sequence Analysis, DNA; Species Specificity
PubMed: 23527149
DOI: 10.1371/journal.pone.0059251 -
Boletin de La Asociacion Medica de... 2012We report a 4 year-old boy with clinical features consistent with the Weaver syndrome. In addition to the typical findings, our patient had tarsal epicanthus,...
We report a 4 year-old boy with clinical features consistent with the Weaver syndrome. In addition to the typical findings, our patient had tarsal epicanthus, intermittent exotropia, hyperopia, and astigmatism. The deletion of the subtelomeric region of 18q has not been previously described in patients with the syndrome. Comparing clinical findings between patients with the de Grouchy and the Weaver syndrome suggest that both entities may be a spectrum of the same disease.
Topics: Abnormalities, Multiple; Child, Preschool; Congenital Hypothyroidism; Craniofacial Abnormalities; Hand Deformities, Congenital; Humans; Male; Puerto Rico
PubMed: 22788078
DOI: No ID Found