Jansen-de Vries syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Jansen-de Vries syndrome is a developmental disorder that affects many parts of the body. Features of this condition include unique facial features, intellectual disability, certain personality characteristics, behavioral changes, and gastrointestinal problems.

The signs and symptoms of Jansen-de Vries syndrome typically begin soon after birth. Affected infants often have low muscle tone (hypotonia) and feeding difficulties. Children with this disorder are often slow to develop speech and language skills, They may also be slow to acquire motor skills, such as standing or walking. People with Jansen-de Vries syndrome also tend to have intellectual disability, which can range from mild to severe.

Additional features seen in people with Jansen-de Vries syndrome may include short stature, small hands and feet, and differences in facial features. The facial features that are common in people with this condition include a broad forehead, thin upper lip, low-set ears that are rotated backwards, and downturned corners of the mouth.

Gastrointestinal problems, such as constipation, are also common in people with Jansen-de Vries syndrome. Many affected individuals experience recurrent episodes of nausea and vomiting (cyclic vomiting).

Though people with Jansen-de Vries syndrome tend to be very social with outgoing and friendly personalities, affected individuals may experience behavioral differences, such as anxiety disorders and attention-deficit hyperactivity disorder. Some people with Jansen-de Vries syndrome have autism-spectrum disorder, a developmental disorder that affects communication and social skills.

Other signs and symptoms of Jansen-de Vries syndrome include vision problems, an increased sensitivity to sound (hyperacusis), and a higher-than-normal pain threshold. Less commonly, people with Jansen-de Vries syndrome can have congenital heart defects. These may include openings in the wall (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Certain variants (sometimes called mutations) in the PPM1D gene cause Jansen-de Vries syndrome. The PPM1D gene provides instructions for making an enzyme called protein phosphatase 1D. This enzyme is present in many of the body's tissues, including the developing brain.

Protein phosphatase 1D belongs to a group of enzymes called the PP2C phosphatases, which regulate cell development in response to environmental stress. In particular, protein phosphatase 1D helps return the cell to its normal state after the cell's DNA has been damaged by environmental agents such as toxic chemicals or radiation.

In addition, protein phosphatase 1D is thought to play a role in regulating areas of tightly packed DNA called heterochromatin. Because gene expression is lower when DNA is tightly packed than when DNA is loosely packed, protein phosphatase 1D helps to turn off (silence) regions of DNA that are not needed.

The variants in the PPM1D gene that cause Jansen-de Vries syndrome typically disrupt the gene's instructions, resulting in an enzyme that does not function as it should. Researchers believe that this enzyme is not able to reach the cell's nucleus. Without enough functional protein phosphatase 1D, gene expression may be altered and cells are not able to fully recover from DNA damage. Researchers are trying to learn exactly how these gene variants affect the developing brain and other body systems to cause the signs and symptoms of Jansen-de Vries 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 altered gene in each cell is sufficient to cause the disorder. Most cases of this condition result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Jansen-de Vries is a rare condition; fewer than 100 cases have been reported in the medical literature.

Which doctor should you see?

The suggested department for discussing Jansen-de Vries 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 Jansen-de Vries 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.