17q12 deletion syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

17q12 deletion syndrome is a condition that results from the deletion of a small piece of chromosome 17 in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q12.

The signs and symptoms of 17q12 deletion syndrome vary widely, even among affected members of the same family. Among the more common features associated with this chromosomal change are problems with development or function of the kidneys and urinary system. These abnormalities range from very severe malformations, leading to kidney failure before birth, to mild or no problems with kidney and urinary tract function. Fluid-filled sacs (cysts) in the kidneys are particularly common. Many affected individuals also develop a form of diabetes called maturity-onset diabetes of the young type 5 (MODY5), which is caused by a malfunction of certain cells in the pancreas. MODY5 usually appears in adolescence or early adulthood, most often before age 25. The combination of kidney cysts and MODY5 is sometimes referred to as renal cysts and diabetes (RCAD) syndrome.

About half of people with 17q12 deletion syndrome have delayed development (particularly speech and language delays), intellectual disability, or behavioral or psychiatric disorders. Neurodevelopmental and psychiatric conditions that have been reported in people with 17q12 deletion syndrome include autism spectrum disorder (which affects social interaction and communication), schizophrenia, anxiety, and bipolar disorder.

Less commonly, 17q12 deletion syndrome also causes abnormalities of the eyes, liver, brain, genitalia, and other body systems. Some females with this chromosomal change have Mayer-Rokitansky-Küster-Hauser syndrome, which is characterized by underdevelopment or absence of the vagina and uterus. 17q12 deletion syndrome is also sometimes associated with subtle differences in facial features.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Most people with 17q12 deletion syndrome are missing about 1.4 million DNA building blocks (base pairs), also written as 1.4 megabases (Mb), at position q12 on chromosome 17. This deletion affects one of the two copies of chromosome 17 in each cell.

The deleted segment is surrounded by short, repeated sequences of DNA that make the segment prone to rearrangement during cell division. The rearrangement can lead to missing or extra copies of DNA at 17q12. (The presence of an extra copy of this segment is called a 17q12 duplication.)

The chromosome segment most commonly deleted in people with 17q12 deletion syndrome contains 15 genes. The loss of two genes in particular, HNF1B and LHX1, is thought to underlie some of the features of 17q12 deletion syndrome. Studies suggest that a loss of one copy of the HNF1B gene in each cell causes the kidney and urinary tract abnormalities, as well as abnormalities of the pancreas that underlie diabetes. The loss of one copy of LHX1 is thought to contribute to intellectual disability, behavioral and psychiatric conditions, and Mayer-Rokitansky-Küster-Hauser syndrome. The loss of other genes in the deleted region may also influence the signs and symptoms that can occur in 17q12 deletion syndrome.

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 chromosomal deletion in each cell is sufficient to cause the disorder.

Most cases of 17q12 deletion syndrome result from a new (de novo) chromosomal deletion and occur in people with no history of the disorder in their family. Less commonly, an affected person inherits the deletion from one affected parent.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The worldwide prevalence of 17q12 deletion syndrome is unknown, although the condition appears to be rare. One study estimated that 17q12 deletion syndrome occurs in 1 in 14,500 people in Iceland.

Which doctor should you see?

The suggested department for discussing 17q12 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 17q12 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.