Ring chromosome 14 syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Ring chromosome 14 syndrome is a condition that is characterized by seizures and intellectual disabilities. In people with ring chromosome 14 syndrome, recurrent seizures (epilepsy) develop during infancy or early childhood. In many cases, these seizures are resistant to treatment with antiseizure medications. Intellectual disabilities are common in people with ring chromosome 14 syndrome and usually range from moderate to severe. In addition, the development of speech and motor skills (such as sitting, standing, and walking) are typically delayed

Some people with ring chromosome 14 syndrome also have behavioral problems, such as hyperactivity or features of autism spectrum disorder, which is characterized by impaired communication and social interaction.

Additional features of ring chromosome 14 syndrome may include:

Various eye abnormalities can be associated with ring chromosome 14 syndrome. These include eyes that do not look in the same direction (strabismus), a clouding of the lenses of the eyes (cataracts), and abnormalities of the specialized tissue at the back of the eye that detects light and color (retina).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Ring chromosome 14 syndrome is caused by a rearrangement of chromosome 14 called ring chromosome 14, sometimes written as r(14). A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and the broken ends fuse together.

Several critical genes near the end of the long (q) arm of chromosome 14 may be lost when the ring chromosome forms. The loss of these genes on one of the two copies of chromosome 14 likely contributes to several of the major features of ring chromosome 14 syndrome, including the intellectual disabilities and developmental delays. In addition, chromosomal rearrangements can disrupt several mechanisms that are involved in the regulation of gene activity (expression), which may also contribute to the features seen in people with ring chromosome 14 syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Ring chromosome 14 syndrome is typically not inherited. A ring chromosome usually occurs as a random event during the formation of reproductive cells (eggs or sperm) or during early embryonic development. In some cases, the ring chromosome is present in only some of a person's cells. This situation is known as mosaicism.

Although most affected individuals have no history of the disorder in their families, there are reports of a ring chromosome being passed from a parent to a child in at least two families.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Because ring chromosome 14 syndrome appears to be extremely rare, its exact prevalence is unknown. More than 80 affected individuals have been reported in the scientific literature.

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.

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.

Seizure · Very frequent (99-80%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Atypical behavior · Frequent (79-30%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Delayed speech and language development · Frequent (79-30%)

A degree of language development that is significantly below the norm for a child of a specified age.

Hypotonia · Frequent (79-30%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Interictal EEG abnormality · Frequent (79-30%)

Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge.

Intrauterine growth retardation · Frequent (79-30%)

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Motor delay · Frequent (79-30%)

A type of Developmental delay characterized by a delay in acquiring motor skills.

Postnatal growth retardation · Frequent (79-30%)

Slow or limited growth after birth.

Recurrent infections · Frequent (79-30%)

Increased susceptibility to infections as manifested by repeated bouts of infection.

Secondary microcephaly · Frequent (79-30%)

Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.

Abnormal corpus callosum morphology · Occasional (29-5%)

Abnormality of the corpus callosum.

Abnormality of retinal pigmentation · Occasional (29-5%)

Any deviation from the normal pigmentation of the retina.

Cafe-au-lait spot · Occasional (29-5%)

Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children.

Other findings in the same source

From: Orphanet

Additional reported features include Cataract (Occasional (29-5%)); Glaucoma (Occasional (29-5%)); Hyperactivity (Occasional (29-5%)); Iris coloboma (Occasional (29-5%)); Myopia (Occasional (29-5%)); Scoliosis (Occasional (29-5%)); Strabismus (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 Ring chromosome 14 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

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

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.