Distal 18q deletion syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Distal 18q deletion syndrome is a chromosomal condition that occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "distal" means that the missing piece occurs near one end of the chromosome. Distal 18q deletion syndrome can lead to a wide variety of signs and symptoms among affected individuals.

Some common features of distal 18q deletion syndrome include short stature (often due to growth hormone deficiency), weak muscle tone (hypotonia), hearing loss due to ear canals that are narrow (aural stenosis) or absent (aural atresia), and foot abnormalities such as an inward or upward-turning foot (clubfoot) or feet with soles that are rounded outward (rocker-bottom feet). Eye movement disorders and other vision problems, an opening in the roof of the mouth (cleft palate), an underactive thyroid gland (hypothyroidism), heart abnormalities that are present from birth (congenital heart defects), kidney problems, genital abnormalities, and skin problems may also occur in this disorder. Some affected individuals have mild facial differences such as deep-set eyes, a flat or sunken appearance of the middle of the face (midface hypoplasia), a wide mouth, and prominent ears. These features are often not noticeable except in a detailed medical evaluation.

Distal 18q deletion syndrome can also affect the nervous system. A common neurological feature of this disorder is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses. The formation of a protective myelin sheath around nerve cells (myelination) normally begins before birth and continues into adulthood. In people with distal 18q deletion syndrome, myelination is often delayed and proceeds more slowly than normal; affected individuals may never have normal adult myelin levels. Most people with distal 18q deletion syndrome have neurological problems, although it is unclear to what extent these problems are related to the dysmyelination. These problems include delayed development, learning disabilities, and intellectual disability that can range from mild to severe. Seizures; hyperactivity; mood disorders such as anxiety, irritability, and depression; and features of autism spectrum disorder that affect communication and social interaction may also occur. Some affected individuals have an unusually small head size (microcephaly).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Distal 18q deletion syndrome is caused by a deletion of genetic material from one copy of chromosome 18 anywhere between a region called 18q21 and the end of the chromosome. The size of the deletion and where it begins vary among affected individuals. The signs and symptoms of distal 18q deletion syndrome are thought to be related to the loss of multiple genes, some of which have not been identified, from this part of chromosome 18. Certain features of the disorder have been associated with the loss of particular genes in this region. People with deletions that include the TCF4 gene usually have signs and symptoms of another genetic condition known as Pitt-Hopkins syndrome, such as severe intellectual disability and breathing problems, in addition to other features of distal 18q deletion syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Distal 18q deletion syndrome is considered to be an autosomal dominant condition, which means one copy of the deleted region on chromosome 18 in each cell is sufficient to cause the disorder's characteristic features.

Most cases of distal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.

In some cases, distal 18q deletion syndrome is inherited, usually from an affected parent with relatively mild signs and symptoms. The condition can also be inherited from an unaffected parent who carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Individuals with a balanced translocation do not usually have any related health problems; however, the translocation can become unbalanced as it is passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Inheritance of an unbalanced translocation that results in the deletion of genetic material from the distal region of the q arm of chromosome 18 causes distal 18q deletion syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Deletions from the q arm of chromosome 18 occur in an estimated 1 in 55,000 newborns worldwide. Most of these deletions occur in the distal region of the q arm, leading to distal 18q deletion syndrome.

Which doctor should you see?

The suggested department for discussing Distal 18q deletion 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 Distal 18q deletion 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.