Home
Diseases
Hematological Neoplasms
Solid tumors
Cancer prone diseases
Case reports
Genes
Gene Reviews
Gene fusions
Education
Deep insights
Educational items 🇬🇧 🇪🇸 🇫🇷 🇩🇪 🇮🇹 🇨🇳
Meetings
Meetings & Events
Submit your event
Donate
News
New Atlas 2.0
Complete human genomed sequenced
HGNC Gene Fusions Nomenclature
Recent Contents
Submit
ARTICLE CONTENTS
To the top
Other actions (beta)
Download as PDF
Weaver syndrome
2007-12-01
Maria Piccione
 ,
Giovanni Corsello
 
Affiliation
Dipartimento Materno Infantile, University of Palermo, Italy
Identity
Name
Weaver syndrome
Note
The Weaver syndrome is characterized by macrocephaly, dysmorphic facial features, accelerated skeletal maturation, limb anomalies, development delay and a predisposition for tumors.
Inheritance
Inheritance is an autosomal dominant nature.
, Etiology: Intragenic mutations in the
NSD1
gene (nuclear receptor binding SET domain protein 1), that have been associated with Sotos syndrome, have been found in patients with Weaver syndrome.The majority of known NSD1 functional domains are in exons 11-23 and all mutations identified were clustered in these domains. The NSD1 mutations in patients with Weaver syndrome are in exons 5, 16, 19, 22 and 23. The identification of NSD1 mutation in patients with Weaver and Sotos syndrome demonstrates that the two conditions are allelic, but it remains possible that separate, second Weaver syndrome gene exists.
, The pathophysiology and the etiology of the other cases remain unknown.
, Although both sexes are affected, the sex ratio is 2M:1F.
Omim
277590
Mesh
C536687
Orphanet
3447 Weaver syndrome
Umls
C0265210
Clinics
Phenotype and clinics
Abnormalities
Growth: persistent overgrowth of prenatal onset and accelerated growth and markedly advanced skeletal maturation during infancy.
Craniofacial: macrocephaly, flat occiput, redundant nuchal skin folds, broad forehead with frontal bossing, thin scalp hair, hypertelorism, upslanting or downslanting palpebral fissures, small palpebral fissures, strabismus, ptosis, broad nasal root, long philtrum, large and dysmorphic ears, micrognathia and highly arched palate.
Skeletal findings: advanced bone age, abnormal or assent femur, splayed metaphyses and mottled epiphyses, broad iliac wings and restricted joint mobility.
Limb anomalies: campotodactyly, prominent finger pads, clinodactyly of fifth finger and toes, broad thumbs, foot deformities (talipes equinovarus, talipes calcaneovalgus, metatarsus adductus, pes adductus and pes cavus), broad iliac wings, cervical kyphosis, cervical spine anomalies and underdevelopment of the mid cervical vertebral bodies.
Performance and Central Nervous System: hypotonia or hypertonia, hoarse voice and development delay.
Tumors: neuroblastoma, malignant ovarian endodermal sinus tumor, sacrococcigeal teratoma and lymphoma.
Occasional abnormalities:
Central nervous System abnormalities: dilation of the ventricles, basal cisterns, sylvian cistern and interhemispheric fissure, cystis of the septum pellucidum, enlarged vessels and hypervascularization in the areas of the middle and left posterior cerebral arterias and pachygiria.
Difficulty in swallowing or breathing is frequent but voracius appetite is present in infant period.
Cardiovascular anomaly: mitral valve prolapse, ventricular septal defect, patent arteriosus ductus and congestive cardiomyopathy.
Umbelical hernia
Inguinal hernia
Cryptorchidism
NF1
associated with café-au-lait spots, Lish nodules, axillary freckling and numerous neurofibromas.
Skeletal anomalies: demineralisation of the bones of the hands and feet.
Table 1: Characteristic clinical features of Weaver syndrome
Differential diagnosis
It is a clinical overlap with other overgrowth syndromes associated with tumors (tab.2)
Table 2: Comparison of Perlman, Beckwith-Wiedemann, Sotos, Weaver and Simpson-Golabi-Behmel syndromes.
Evolution
Multidisciplinary management (pediatric, orthopaedic, neurological, Cardiological care etc. ) is necessary. X-ray cervical spine is necessary. Cervical spine anomalies represent a consistent radiographic finding in Weaver syndrome. The brain abnormalities reported in some cases suggest that MRI should be considered as part of the follow-up. The tumors occur in Weaver syndrome more commonly than expected ( 5 patients described). Since two patients have had neuroblastoma, retroperitoneal ultrosonography is suggested every 3 month from 0-3 years, every 6 month from 3-6 years and 1 once a year up to the age of 12.
Prognosis
Prognosis is variable, most patients have normal life span and the clinical findings in adults with Weaver syndrome are subtle.
Article Bibliography
Pubmed ID
Last Year
Title
Authors
2418189
1986
Further delineation of Weaver syndrome.
Ardinger HH et al
10559762
1999
Recognition and management of childhood cancer syndromes: a systems approach.
Clericuzio CL et al
1583661
1992
Weaver syndrome.
Cole TR et al
10507738
1999
A probable case of familial Weaver syndrome associated with neoplasia.
Derry C et al
12464997
2003
NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.
Douglas J et al
8131308
1993
Twins and their mildly affected mother with Weaver syndrome.
Dumić M et al
3993681
1985
Update on the Marshall-Smith-Weaver controversy.
Fitch N et al
10494098
1999
Pachygyria in Weaver syndrome.
Freeman BM et al
9152841
1997
Autosomal dominant inheritance of Weaver syndrome.
Fryer A et al
7441429
1980
The Weaver-Smith syndrome.
Gemme G et al
4080734
1985
Weaver syndrome: expanded natural history.
Hall BD et al
11241499
2001
Weaver syndrome with neuroblastoma and cardiovascular anomalies.
Huffman C et al
11146472
2000
Cervical spine anomalies and tumors in Weaver syndrome.
Kelly TE et al
7318839
1981
The Weaver syndrome: a rare type of primordial overgrowth.
Majewski F et al
6641769
1983
The Weaver syndrome in a girl.
Meinecke P et al
2319408
1990
Weaver syndrome and instability of the upper cervical spine.
Muhonen MG et al
9781911
1998
The syndromes of Sotos and Weaver: reports and review.
Opitz JM et al
9781912
1998
Weaver syndrome: autosomal dominant inheritance of the disorder.
Proud VK et al
12807965
2003
Spectrum of NSD1 mutations in Sotos and Weaver syndromes.
Rio M et al
10441697
1999
A case with Weaver syndrome operated for congenital cardiac defect.
Sarigül A et al
8725789
1996
Novel findings in a patient with Weaver or a Weaver-like syndrome.
Scarano G et al
2369050
1990
[Weaver's syndrome. Apropos of a new case].
Trabelsi M et al
4366187
1974
A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly.
Weaver DD et al
7318847
1981
Accelerated bone maturation syndrome of the Weaver type.
Weisswichert PH et al
9598729
1998
Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome.
van Asperen CJ et al
External Links
GARD
ERN GENTURIS
OMIM
ORPHANET
MeSH
Generate PDF
×
Please, confirm that you want to generate a PDF file of this page.
This may take some seconds once process has started. Then it will be opened automatically.
Wait a moment, we are generating the document...
Aditional Info
×
Loading, wait...