CHST3-related skeletal dysplasia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

CHST3-related skeletal dysplasia is a genetic condition characterized by bone and joint abnormalities that worsen over time. Affected individuals have short stature throughout life, with an adult height under 4 and a half feet. Joint dislocations, most often affecting the knees, hips, and elbows, are present at birth (congenital). Other bone and joint abnormalities can include an inward- and upward-turning foot (clubfoot), a limited range of motion in large joints, and abnormal curvature of the spine. The features of CHST3-related skeletal dysplasia are usually limited to the bones and joints; however, minor heart defects have been reported in a few affected individuals.

Researchers have not settled on a preferred name for this condition. It is sometimes known as autosomal recessive Larsen syndrome based on its similarity to another skeletal disorder called Larsen syndrome. Other names that have been used to describe the condition include spondyloepiphyseal dysplasia, Omani type; humero-spinal dysostosis; and chondrodysplasia with multiple dislocations. Recently, researchers have proposed the umbrella term CHST3-related skeletal dysplasia to refer to bone and joint abnormalities resulting from mutations in the CHST3 gene.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

As its name suggests, CHST3-related skeletal dysplasia results from mutations in the CHST3 gene. This gene provides instructions for making an enzyme called C6ST-1, which is essential for the normal development of cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the CHST3 gene reduce or eliminate the activity of the C6ST-1 enzyme. A shortage of this enzyme disrupts the normal development of cartilage and bone, resulting in the abnormalities associated with CHST3-related skeletal dysplasia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of CHST3-related skeletal dysplasia is unknown. More than 30 affected individuals have been reported.

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 form of the vertebral bodies · Very frequent (99-80%)

Abnormal form of vertebral body, which is the central cylindrical portion of the vertebra that together with other structures such as the vertebral arch, pedicles, laminae, spinous process, transverse processes, and articular facets makes up a vertebra.

Abnormality of the elbow · Very frequent (99-80%)

An anomaly of the joint that connects the upper and the lower arm.

Arthralgia · Very frequent (99-80%)

Joint pain.

Barrel-shaped chest · Very frequent (99-80%)

A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.

Brachydactyly · Very frequent (99-80%)

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Cubitus valgus · Very frequent (99-80%)

Abnormal positioning in which the elbows are turned out.

Disproportionate short-trunk short stature · Very frequent (99-80%)

A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.

Enlarged joints · Very frequent (99-80%)

Increase in size of one or more joints.

Flexion contracture · Very frequent (99-80%)

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Genu valgum · Very frequent (99-80%)

The legs angle inward, such that the knees are close together and the ankles far apart.

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).

Intervertebral space narrowing · Very frequent (99-80%)

Decreased height of the intervertebral disk.

Irregular epiphyses · Very frequent (99-80%)

An alteration of the normally smooth contour of the epiphysis leading to an irregular appearance.

Rhizomelia · Very frequent (99-80%)

Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).

Other findings in the same source

From: Orphanet

Additional reported features include Scoliosis (Very frequent (99-80%)); Small epiphyses (Very frequent (99-80%)); Sparse eyebrow (Very frequent (99-80%)); Waddling gait (Very frequent (99-80%)); Abnormal cardiovascular system morphology (Frequent (79-30%)); Broad forehead (Frequent (79-30%)); Delayed eruption of teeth (Frequent (79-30%)); Highly arched eyebrow (Frequent (79-30%)); Kyphoscoliosis (Frequent (79-30%)); Long philtrum (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing CHST3-related skeletal dysplasia is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

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.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for CHST3-related skeletal dysplasia. 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.