Jackson-Weiss syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Jackson-Weiss syndrome is a genetic disorder characterized by foot abnormalities and the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.

Many of the characteristic facial features of Jackson-Weiss syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to a misshapen skull, widely spaced eyes, and a bulging forehead.

Foot abnormalities are the most consistent features of Jackson-Weiss syndrome. The first (big) toes are short and wide, and they bend away from the other toes. Additionally, the bones of some toes may be fused together (syndactyly) or abnormally shaped. The hands are almost always normal.

Some individuals with Jackson-Weiss syndrome have hearing impairment. People with Jackson-Weiss syndrome usually have normal intelligence and a normal life span.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the FGFR2 gene cause Jackson-Weiss syndrome. This gene provides instructions for making a protein called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become bone cells during embryonic development. A mutation in a specific part of the FGFR2 gene overstimulates signaling by the FGFR2 protein, which promotes the premature fusion of skull bones and affects the development of bones in the feet.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Jackson-Weiss syndrome is a rare genetic disorder; its incidence is unknown.

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.

Broad hallux phalanx · Very frequent (99-80%)

An increase in width in one or more phalanges of the big toe.

Broad metatarsal · Very frequent (99-80%)

Increased side-to-side width of a metatarsal bone.

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).

Midface retrusion · Very frequent (99-80%)

Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.

Short metatarsal · Very frequent (99-80%)

Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.

Toe syndactyly · Very frequent (99-80%)

Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".

Turricephaly · Very frequent (99-80%)

Tall head relative to width and length.

Abnormal palate morphology · Frequent (79-30%)

Any abnormality of the palate, i.e., of roof of the mouth.

Convex nasal ridge · Frequent (79-30%)

Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.

Frontal bossing · Frequent (79-30%)

Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.

Hypoplasia of the maxilla · Frequent (79-30%)

Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.

Mandibular prognathia · Frequent (79-30%)

Abnormal prominence of the chin related to increased length of the mandible.

Proptosis · Frequent (79-30%)

An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Ptosis · Frequent (79-30%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Other findings in the same source

From: Orphanet

Additional reported features include Strabismus (Frequent (79-30%)); Underdeveloped supraorbital ridges (Frequent (79-30%)); 2-3 toe syndactyly (Occasional (29-5%)); Abnormal fibula morphology (Occasional (29-5%)); Preaxial foot polydactyly (Occasional (29-5%)); Split foot (Occasional (29-5%)); Symphalangism affecting the phalanges of the hand (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Jackson-Weiss 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 Jackson-Weiss 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.