Weaver syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Weaver syndrome is a condition that involves tall stature with or without a large head size (macrocephaly), a variable degree of intellectual disability (usually mild), and characteristic facial features. These features can include a broad forehead; widely spaced eyes (hypertelorism); large, low-set ears; a dimpled chin, and a small lower jaw (micrognathia).

People with Weaver syndrome can also have joint deformities called contractures that restrict the movement of affected joints. The contractures may particularly affect the fingers and toes, resulting in permanently bent digits (camptodactyly). Other features of this disorder can include abnormal curvature of the spine (kyphoscoliosis); muscle tone that is either reduced (hypotonia) or increased (hypertonia); loose, saggy skin; and a soft-outpouching around the belly-button (umbilical hernia). Some affected individuals have abnormalities in the folds (gyri) of the brain, which can be seen by medical imaging; the relationship between these brain abnormalities and the intellectual disability associated with Weaver syndrome is unclear.

Researchers suggest that people with Weaver syndrome may have an increased risk of developing cancer, in particular a slightly increased risk of developing a tumor called neuroblastoma in early childhood, but the small number of affected individuals makes it difficult to determine the exact risk.

ORPHANET DEFINITION A rare PRC-2 complex-related overgrowth spectrum disorder characterized by pre- and post-natal overgrowth, facial dysmorphism (including hypertelorism, large fleshy ears and retrognathia with the appearance of a 'stuck-on' chin with associated horizontal skin crease) that is easily recognizable in early childhood. Majority of the patients present with mild intellectual disability. Additional variable features include macrocephaly, joint laxity, scoliosis, pectus excavatum, hypo- and/or hypertonia, poor coordination, soft dough skin, clinodactyly, camptodactyly of the fingers and/or toes, umbilical hernia, and a low hoarse cry in infancy. Many clinical features, including facial dysmorphism, attenuate with age. Patients may also have a higher risk of neuroblastoma.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 48.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal fingernail morphology · Very frequent (99-80%)

An abnormality of the fingernails.

Abnormal metaphysis morphology · Very frequent (99-80%)

An abnormality of one or more metaphysis, i.e., of the somewhat wider portion of a long bone that is adjacent to the epiphyseal growth plate and grows during childhood.

Abnormally low-pitched voice · Very frequent (99-80%)

A persistent (minutes to hours) abnormal decrease in the pitch of the voice for the context or social situation or significantly different from the baseline of the individual.

Accelerated skeletal maturation · Very frequent (99-80%)

An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.

Broad forehead · Very frequent (99-80%)

Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.

Deep-set nails · Very frequent (99-80%)

Deeply placed nails.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Hoarse voice · Very frequent (99-80%)

Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.

Hypertelorism · Very frequent (99-80%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Hypertonia · Very frequent (99-80%)

A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.

Hypoplastic toenails · Very frequent (99-80%)

Underdevelopment of the toenail.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Long philtrum · Very frequent (99-80%)

Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.

Macrocephaly · Very frequent (99-80%)

Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Other findings in the same source

From: Orphanet

Additional reported features include Macrotia (Very frequent (99-80%)); Micrognathia (Very frequent (99-80%)); Posteriorly rotated ears (Very frequent (99-80%)); Redundant skin (Very frequent (99-80%)); Retrognathia (Very frequent (99-80%)); Spasticity (Very frequent (99-80%)); Tall stature (Very frequent (99-80%)); Thin nail (Very frequent (99-80%)); Broad foot (Frequent (79-30%)); Broad thumb (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 48.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Weaver syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Weaver syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.