Weaver syndrome

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Other Names

Weaver Smith syndrome; WSS; Overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly

Clinical features

Weaver syndrome is a rare condition that is characterized primarily by tall stature. Other signs and symptoms of the condition may include macrocephaly (unusually large head size); intellectual disability; distinctive facial features; camptodactyly (permanently bent digits) of the fingers and/or toes; poor coordination; soft and doughy skin; umbilical hernia; abnormal muscle tone; and a hoarse, low-pitched cry during infancy. Some studies also suggest that people affected by Weaver syndrome may have an increased risk of developing neuroblastoma.

Incidence

Weaver syndrome is rare and affects about 1 in 15,000 cases

Cause

Weaver syndrome is usually caused by changes (mutations) in the EZH2 gene.

Inheritance

Although the condition is considered autosomal dominant, most cases occur as de novo mutations in people with no family history of the condition.

Autosomal Dominant Inheritance

Symptoms

80%-99% of people have these symptoms

• Abnormality of the metaphysis
• Abnormally low-pitched voice
• Accelerated skeletal maturation
• Broad forehead
• Deep-set nails
• Global developmental delay
• Hoarse voice
• Hypertelorism
• Hypoplastic toenails
• Intellectual disability
• Long philtrum
• Low-set, posteriorly rotated ears
• Macrocephaly
• Macrotia
• Micrognathia
• Redundant skin
• Retrognathia
• Spasticity
• Tall stature
• Thin nail

30%-79% of people have these symptoms

• Broad foot
• Broad thumb
• Camptodactyly of finger
• Deep philtrum
• Feeding difficulties in infancy
• Fine hair
• Inguinal hernia
• Joint stiffness
• Large hands
• Round face

5%-29% of people have these symptoms

• Abnormality of cardiovascular system morphology
• Cryptorchidism
• Down-slanted palpebral fissures
• Finger syndactyly
• Hypoplasia of penis
• Joint hyperflexibility
• Pes cavus
• Sandal gap
• Scoliosis
• Talipes equinovarus

Less common symptoms

• Absent septum pellucidum
• Autosomal dominant inheritance
• Behavioral abnormality
• Calcaneovalgus deformity
• Camptodactyly
• Clinodactyly
• Coxa valga
• Cutis laxa
• Delayed speech and language development
• Depressed nasal bridge
• Diastasis recti
• Dilation of lateral ventricles
• Dimple chin
• Dysarthria
• Dysharmonic bone age
• Epicanthus
• Flared femoral metaphysis
• Flared humeral metaphysis
• Generalized hypotonia
• Hydrocele testis
• Hypertonia
• Hypoplastic iliac wing
• Inverted nipples
• Joint contracture of the hand
• Kyphosis
• Limited elbow extension
• Limited knee extension
• Mandibular prognathia
• Metatarsus adductus
• Muscular hypotonia
• Overlapping toe
• Prominent fingertip pads
• Radial deviation of finger
• Seizure
• Short fourth metatarsal
• Short ribs
• Slurred speech
• Sparse hair
• Strabismus
• Umbilical hernia

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging and a detailed history including family history, imaging studies, blood work, and genetic testing.

Treatment

• Treatment is based on the signs and symptoms present in each person.
• 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. Surgery may be used to correct any skeletal issues.
• Physical and occupational therapy are considered an option to help with muscle tone. Speech therapy is often recommended for speech related problems.

Prognosis

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.

History

The condition was first described by American physician David Weaver in 1974.

Latest research (Pubmed)

• Most recent articles
• Ongoing trials

• Weaver syndrome(Weaver-Smith syndrome)

Matsuo M. Ryoikibetsu Shokogun Shirizu. 2001;(34 Pt 2):806-7. PMID: 11529033 Review. Japanese. No abstract available.

• Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.

Tatton-Brown K, Murray A, Hanks S, Douglas J, Armstrong R, Banka S, Bird LM, Clericuzio CL, Cormier-Daire V, Cushing T, Flinter F, Jacquemont ML, Joss S, Kinning E, Lynch SA, Magee A, McConnell V, Medeira A, Ozono K, Patton M, Rankin J, Shears D, Simon M, Splitt M, Strenger V, Stuurman K, Taylor C, Titheradge H, Van Maldergem L, Temple IK, Cole T, Seal S; Childhood Overgrowth Consortium, Rahman N. Am J Med Genet A. 2013 Dec;161A(12):2972-80. doi: 10.1002/ajmg.a.36229. Epub 2013 Nov 8. PMID: 24214728 Free article. Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome.

• Weaver syndrome with neuroblastoma and cardiovascular anomalies

Huffman C, McCandless D, Jasty R, Matloub J, Robinson HB, Weaver DD, Cohen MM Jr. Am J Med Genet. 2001 Mar 15;99(3):252-5. doi: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1169>3.0.co;2-l. PMID: 11241499 We report on an infant with Weaver syndrome, neoplasia and cardiovascular anomalies. Stage 4S neuroblastoma underwent spontaneous resolution.

• Weaver syndrome and neuroblastoma

Coulter D, Powell CM, Gold S. J Pediatr Hematol Oncol. 2008 Oct;30(10):758-60. doi: 10.1097/MPH.0b013e3181758974. PMID: 19011474 Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia.

• Recommendations for Cancer Surveillance in Individuals with RASopathies and Other Rare Genetic Conditions with Increased Cancer Risk.

Villani A, Greer MC, Kalish JM, Nakagawara A, Nathanson KL, Pajtler KW, Pfister SM, Walsh MF, Wasserman JD, Zelley K, Kratz CP. Clin Cancer Res. 2017 Jun 15;23(12):e83-e90. doi: 10.1158/1078-0432.CCR-17-0631. PMID: 28620009 Free article. Review. For all syndromes, the panel recommends increased awareness and prompt assessment of clinical symptoms. Patients with Costello syndrome have the highest cancer risk, and cancer surveillance should be considered.

• Weaver syndrome

Tsukahara M, Tsujino K. Ryoikibetsu Shokogun Shirizu. 2000;(30 Pt 5):258-9. PMID: 11057220 Review. No abstract available

Frequently asked questions

• What causes Weaver syndrome?
• Is Weaver Syndrome a disability?
• How is Weaver syndrome inherited?
• What is the life expectancy of someone with Weaver syndrome?
• What are the differences between weavers and Soto's syndrome?

See also

• Beckwith–Wiedemann syndrome
• Perlman syndrome
• Sotos syndrome

• Wikipedia