12q14 microdeletion syndrome

What it is

From: Orphanet

12q14 microdeletion syndrome is characterised by mild intellectual deficit, failure to thrive, short stature and osteopoikilosis. It has been described in four unrelated patients. The syndrome appears to be caused by a heterozygous deletion at chromosome region 12q14, which was detected in three of the four patients. The deleted region contains the LEMD3 gene: mutations in this gene have already been implicated in osteopoikilosis.

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.

Delayed speech and language development · Very frequent (99-80%)

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

Failure to thrive · Very frequent (99-80%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

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.

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).

Intellectual disability, mild · Very frequent (99-80%)

Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69.

Intrauterine growth retardation · Very frequent (99-80%)

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

Short stature · Very frequent (99-80%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Specific learning disability · Very frequent (99-80%)

Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.

Hyperpigmentation of the skin · Frequent (79-30%)

A darkening of the skin related to an increase in melanin production and deposition.

Osteopoikilosis · Frequent (79-30%)

Osteopoikilosis is a benign, asymptomatic sclerotic dysplasia of the bones. It affects both male and female and may be seen at any age. Radiographically sclerotic circular or ovoid lesions are usually symmetrically distributed in a periarticular location. Lesions can increase or decrease in size and number in serial radiographs or even disappear and do not have increased bone radiotracer uptake.

Tremor · Frequent (79-30%)

An unintentional, oscillating to-and-fro muscle movement about a joint axis.

Abnormality of the nares · Occasional (29-5%)

Abnormality of the nostril.

Abnormality of the spleen · Occasional (29-5%)

An abnormality of the spleen.

Chiari malformation · Occasional (29-5%)

Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow.

Other findings in the same source

From: Orphanet

Additional reported features include Clinodactyly of the 5th finger (Occasional (29-5%)); Deeply set eye (Occasional (29-5%)); Diabetes mellitus (Occasional (29-5%)); Downturned corners of mouth (Occasional (29-5%)); Ectopic kidney (Occasional (29-5%)); Frontal bossing (Occasional (29-5%)); Horseshoe kidney (Occasional (29-5%)); Hypodontia (Occasional (29-5%)); Hypotonia (Occasional (29-5%)); Intestinal malrotation (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood

Inheritance in the source

From: Orphanet

Unknown

Frequency and the population described

From: Orphanet

Reported case(s): 22.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing 12q14 microdeletion syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

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

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 12q14 microdeletion 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.