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Weaver Syndrome

Camptodactyly-Overgrowth-Unusual Facies Syndrome

Weaver syndrome is a very rare genetic disorder that presents with a range of musculoskeletal, cutaneous, cognitive, and facial symptoms. Excessive growth in early life is the most prominent finding, followed by intellectual disability of various degrees and connective tissue disorders such as laxity of ligaments. The diagnosis rests on a thorough clinical assessment, which is the only tool to raise sufficient evidence for genetic testing.


Initially described in the 1970s, Weaver syndrome is a very rare congenital genetic disorder, with little over 50 cases described in the literature [1] [2] [3] [4]. Until recently, the exact pathogenesis of this condition was unknown, but new results strongly point toward mutations of the Enhancer of Zeste Drosophila homolog 2 (EZH2) gene [1] [2] [3] [5] [6]. EZH2 is an important regulator of epigenetic functions and the process of transcription and is well-known for its prominent role in the maturation of skeletal, muscle, lymphoid, and blood cells [6] [7]. The exact mechanism of mutation is yet to be solidified, although missense mutations were most frequently identified so far [1] [2]. The clinical presentation involves several organ systems from early life and the most important component is excessive generalized growth leading to tall stature [1] [2] [3]. Hypertelorism and advanced bone age are frequent findings, whereas other notable findings of the musculoskeletal system are scoliosis, talipes equinovarus, and camptodactyly (fixed flexion of fingers) [1] [2] [3]. Cranial abnormalities, such as macrocephaly, and several characteristic features of the face (retrognathia, a broad forehead, round facies, large ears, and very wide eyes) are commonly present [1] [4]. Intellectual impairment is an equally important component of the clinical presentation, varying from mild to severe and debilitating IQ deficits [1] [2]. Poor coordination, owing to the extreme laxity of ligaments, and very loose skin are additional findings in patients suffering from Weaver syndrome [4].

Broad Thumb
  • thumb Broad thumbs Wide/broad thumb [ more ] 0011304 Camptodactyly of finger Permanent flexion of the finger 0100490 Deep philtrum 0002002 Feeding difficulties in infancy 0008872 Fine hair Fine hair shaft Fine hair texture Thin hair shaft Thin hair texture[rarediseases.info.nih.gov]
  • Limb abnormalities include prominent finger pads, camptodactyly, broad thumbs, thin and deep-set nails, clinodactyly, limited elbow and knee extension, wide distal long bones, and foot deformities (clubfoot, pes calcaneovalgus, and metatarsus adductus[sites.google.com]
  • Limb abnormalities consist of prominent finger pads, thin and deeply-set nails, camptodactyly, wide distal long bones, foot deformities, and broad thumbs.[cags.org.ae]
  • 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[atlasgeneticsoncology.org]
  • Rubinstein–Taybi Syndrome Rubinstein–Taybi syndrome (RSTS) is characterized by facial features, including down-slanting palpebral fissures, low columella, high palate, grimacing smile, and talon cusps, broad thumbs and great toes, short stature, and intellectual[clincancerres.aacrjournals.org]
Sparse Hair
  • Tall, broad, prominent forehead, sparse hair in frontotemporal region. Hypertelorism, downslanting palpebral fissures, epicanthal folds Retrognathia & with prominent chin crease ("stuck on chin").[genetics4medics.com]
  • hair 0008070 Strabismus Cross-eyed Squint Squint eyes [ more ] 0000486 Umbilical hernia 0001537[rarediseases.info.nih.gov]
Advanced Bone Age
  • Abstract Accelerated growth and advanced bone age are consistent findings in Weaver-Smith syndrome (WSS).[ncbi.nlm.nih.gov]
  • In addition to the characteristic manifestations of overgrowth and advanced bone age, the facies were typical, with a broad forehead, hypertelorism, a long philtrum, micrognathia, and large ears.[ncbi.nlm.nih.gov]
  • Abstract Weaver syndrome is a rare disorder of unknown etiology characterized by skeletal overgrowth, distinctive craniofacial and digital abnormalities, and advanced bone age.[ncbi.nlm.nih.gov]
  • Weaver syndrome is a genetic disorder in which children show accelerated bone growth, advanced bone age and a characteristic appearance of the face. Weaver syndrome or Weaver-Smith syndrome was first described in 1974 by Weaver and his colleagues.[medindia.net]
  • 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.[ncbi.nlm.nih.gov]
Large Hand
  • Weaver's syndrome is characterised by excessive growth, large ears, large hands and thumb, protuberant lower lip, hypertelorism, limited knee and elbow extension, kyphosis and mental retardation.[gpnotebook.co.uk]
  • hands large hand 0001176 Round face Circular face Round facial appearance Round facial shape [ more ] 0000311 5%-29% of people have these symptoms Abnormality of cardiovascular system morphology 0030680 Cryptorchidism Undescended testes Undescended testis[rarediseases.info.nih.gov]
  • In addition to her abnormally tall height, and large hands and feet, Rumeysa also has a very large head which is characteristic of the Weaver’s syndrome.[futurescienceleaders.com]
  • hands and feet Persistent feeding difficulties and / or reflux Characteristic structural changes in the brain on MRI Down-slanting palpebral fissues or "antimongoloid slant" ASMS Heart defects Treatment for Sotos syndrome is based upon the symptoms the[sotossyndrome.co.uk]
Coxa Valga
  • valga 0002673 Cutis laxa Loose and inelastic skin 0000973 Delayed speech and language development Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language[rarediseases.info.nih.gov]
Extension of Elbows Limited
  • Elbow limited extension Limitation of elbow extension Limited extension at elbows Limited forearm extension Restricted elbow extension [ more ] 0001377 Limited knee extension 0003066 Mandibular prognathia Big lower jaw Increased projection of lower jaw[rarediseases.info.nih.gov]
Short Neck
  • The prime anesthetic problem reported in children with Weaver syndrome is difficulty with tracheal intubation, resulting in part from relative micrognathia, short neck, and an anterior and cephalad position of the larynx.[ncbi.nlm.nih.gov]
Slurred Speech
  • speech 0001350 Sparse hair 0008070 Strabismus Cross-eyed Squint Squint eyes [ more ] 0000486 Umbilical hernia 0001537[rarediseases.info.nih.gov]


Given the very rare occurrence of Weaver syndrome (and its still incompletely understood mechanism of inheritance), the diagnosis can be quite difficult to make. For this reason, the physician should obtain a comprehensive patient history that will cover the onset of symptoms and their progression, as well as severity. Because isolated cases of parent-to-child transmission were confirmed [4], a thorough family history may yield important information and should not be overlooked in patients with undisclosed complaints from early life. A detailed physical examination should follow history taking, during which the assessment of growth curves, facial features, and cognitive status must be evaluated. The initial recognition of Weaver syndrome primarily rests on clinical criteria, but the nonspecific clinical presentation that often lacks some of its main components significantly impedes recognition [2]. In order to confirm the diagnosis, genetic testing needs to be employed [1]. Detection of a pathogenic variant of EZH2 through molecular and proband testing strengthens the diagnosis [1]. In addition to clinical and laboratory studies, imaging techniques, such as magnetic resonance imaging (MRI), may be useful for patients in whom macrocephaly is suspected, as ventriculomegaly and several other findings can be observed [1].


  • This paper describes a patient with Weaver syndrome, referred for consultation and treatment of macroglossia, who also suffered from congenital hypothyroidism.[ncbi.nlm.nih.gov]
  • Treatment - Weaver syndrome There is no cure available for Weaver syndrome. However, with multidisciplinary management such as neurological, pediatric, orthopedic, and psychomotor care and genetic counseling, symptoms can be managed.[checkorphan.org]
  • INTERVENTIONS: Treatment was initiated bolus injections of ephedrine, epinephrine, lidocaine, steroids and antihistaminic and continued with lidocaine bolus dosages and norepinephrine infusion for the postoperative period.[ncbi.nlm.nih.gov]
  • It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice .[uniprot.org]
  • Speech therapy may help with speech, and behavioral assessments and treatments may help with behavioral problems. Prognosis With appropriate treatment and management, children with Weaver syndrome appear to do well.[encyclopedia.com]


  • Prognosis - Weaver Williams syndrome Not supplied. Treatment - Weaver Williams syndrome Not supplied. Resources - Weaver Williams syndrome Not supplied.[checkorphan.org]
  • Prognosis - Weaver syndrome With appropriate treatment and management, patients with Weaver syndrome appear to do well, both physically and intellectually, throughout their life and have a normal lifespan. Their adult height is normal as well.[checkorphan.org]
  • Prognosis varies with every case as some patients retain a normal life span and with an ordinary adult height.[cags.org.ae]
  • 80%) mottled or irregular epiphyses (44%) Endocrine no consistent abnormalities noted MANAGEMENT: Supportive no treatment available for underlying disorder multidisciplinary approach Paediatrics, Neurology, Orthopedics, ENT, OT, PT genetic counselling Prognosis[sites.google.com]
  • Prognosis Prognosis is variable, most patients have normal life span and the clinical findings in adults with Weaver syndrome are subtle. Further delineation of Weaver syndrome.[atlasgeneticsoncology.org]


  • The etiology of the syndrome remains unclear, but if genetic, X-linked recessive inheritance can be excluded.[ncbi.nlm.nih.gov]
  • Weaver syndrome is a very rare disorder of unknown etiology characterized by accelerated growth of prenatal onset, advanced osseous maturation, special craniofacial features, umbilical hernia, and hoarse low-pitched cry.[ncbi.nlm.nih.gov]
  • Abstract Weaver syndrome is a rare disorder of unknown etiology characterized by skeletal overgrowth, distinctive craniofacial and digital abnormalities, and advanced bone age.[ncbi.nlm.nih.gov]
  • Statistics: EPIDEMIOLOGY: incidence: rare (over 30 cases reported) age of onset: newborn - infancy (excessive growth first noted) risk factors: sporadic M F (3:1) PATHOGENESIS: Background unknown etiology syndrome first described in 1974 by Weaver et[sites.google.com]


  • The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations.[books.google.de]
  • Author information 1 Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK. Abstract The biological processes controlling human growth are diverse, complex and poorly understood.[ncbi.nlm.nih.gov]
  • Statistics: EPIDEMIOLOGY: incidence: rare (over 30 cases reported) age of onset: newborn - infancy (excessive growth first noted) risk factors: sporadic M F (3:1) PATHOGENESIS: Background unknown etiology syndrome first described in 1974 by Weaver et[sites.google.com]
  • Author information 1 Division of Genetics & Epidemiology, Institute of Cancer Research, Sutton, UK.[ncbi.nlm.nih.gov]
  • Epidemiological insights into the public health burden of sleep disordered breathing: sex differences into survival among sleep clinic patients. Thorax (1998) 53(suppl 3): 16-19. 3. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP.[medichub.ro]
Sex distribution
Age distribution


  • The pathophysiology and the etiology of the other cases remain unknown. Although both sexes are affected, the sex ratio is 2M:1F.[atlasgeneticsoncology.org]
  • The pathophysiology of OSAHS is responsible for the signs, symptoms and consequences, and is represented by repetitive episodes of collapse of the upper airway.[medichub.ro]
  • Pathophysiological relevance and possible prognostic value. Lancet , 1(8175): 947-9 [ PM ] [ EČ ][ GS ] Hulman, G. (1988) Pathogenesis of non-traumatic fat embolism.[scindeks.ceon.rs]


  • […] syndrome Short rib polydactyly syndrome Filippi syndrome 49,XXXXX syndrome Aicardi Goutieres syndrome Allan-Herndon-Dudley syndrome Alpha thalassaemia X-linked mental retardation syndrome Alpha-thalassemia/mental retardation syndrome, deletion type Prevention[checkorphan.org]
  • Symptoms - Weaver syndrome Prevention - Weaver syndrome Not supplied.[checkorphan.org]
  • Growth disorders are problems that prevent children from developing normal height, weight, sexual maturity or other features. Very slow or very fast growth can sometimes signal a gland problem or disease.[medlineplus.gov]
  • Recombinant EZH2 activity measured using a fluorescent histone H3 lysine 27 methyltransferase assay. for Recombinant EZH2 protein complex Storage Recombinant proteins in solution are temperature sensitive and must be stored at -80 C to prevent degradation[activemotif.com]
  • EZH2 regulates gene expression to prevent differentiation of stem and progenitor cells, and aberrant EZH2 activity is implicated as an oncogenic driver.[abstracts.asco.org]



  1. Tatton-Brown K, Rahman N. EZH2-Related Overgrowth. 2013 Jul 18 [Updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  2. Tatton-Brown K, Murray A, Hanks S, et al. Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype. Am J Med Genet A. 2013;161A:2972–80.
  3. Fryer A., Smith C., Rosenbloom L., Cole T. Autosomal dominant inheritance of Weaver syndrome. J. Med. Genet. 1997;34:418–419
  4. Gibson WT, Hood RL, Zhan SH, et al. Mutations in EZH2 Cause Weaver Syndrome. Am J Hum Genet. 2012;90(1):110-118.
  5. Bansal N, Bansal A. Weaver syndrome: A report of a rare genetic syndrome. Indian J Hum Genet. 2009;15(1):36-37.
  6. Tatton-Brown K, Hanks S, Ruark E, et al. Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget. 2011;2(12):1127-1133.
  7. Chou RH, Yu YL, Hung MC. The roles of EZH2 in cell lineage commitment. Am J Transl Res. 2011;3:243–250.

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Last updated: 2018-06-22 09:07