Potocki-Lupski syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Lupski syndrome is caused by a duplication of a small piece of chromosome 17 in each cell. Major features of the condition include developmental delays, intellectual disabilities, sleep problems, and behavioral difficulties. However, the specific signs and symptoms of Potocki-Lupski syndrome can vary among affected individuals.

Infants with Potocki-Lupski syndrome may have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia) that lead to feeding problems. Because some affected infants do not grow and gain weight at the expected rate (faltering weight), children with Potocki-Lupski syndrome may be shorter and weigh less than their peers. Up to 40 percent of babies with Potocki-Lupski syndrome are born with a heart defect, which can be life-threatening.

Children with Potocki-Lupski syndrome typically have speech delays and delayed development of motor skills, such as sitting, standing, and walking. As they get older, affected individuals may have ongoing difficulties with speech and language. Intellectual disabilities in people with Potocki-Lupski syndrome can range from mild to severe, but they often fall within the mild to moderate range.

Potocki-Lupski syndrome may be associated with behavioral difficulties, which can include attention problems, hyperactivity, compulsive or impulsive behaviors, and anxiety. Affected individuals may also have characteristics of autism spectrum disorder, a condition that affects social interaction and communication.

Many individuals with Potocki-Lupski syndrome have problems with sleep, including short pauses in breathing during sleep (sleep apnea). Other signs and symptoms of Potocki-Lupski syndrome can include vision and hearing problems, dental abnormalities, and abnormal kidney development and function.

People with Potocki-Lupski syndrome may also have subtle differences in their facial features, including a downward slant to the outside corners of their eyes (down-slanting palpebral fissures), a triangular face with a broad forehead and a small jaw (micrognathia), and widely spaced eyes (hypertelorism).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Lupski syndrome is caused by a duplication of genetic material on the short (p) arm of chromosome 17 at 17p11.2. As a result, Potocki-Lupski syndrome is also known as 17p11.2 duplication syndrome. In about two-thirds of affected individuals, the duplicated segment includes approximately 3.7 million DNA building blocks (base pairs), also written as 3.7 megabases (Mb). In the remaining cases, the duplication is larger or smaller. All of the duplications known to cause Potocki-Lupski syndrome contain the RAI1 gene. Studies suggest that having an extra copy of the RAI1 gene is responsible for many of the characteristic features of the condition.

The RAI1 gene provides instructions for making a protein that helps regulate the activity (expression) of other genes. This protein appears to play a role in the developing brain and helps control the expression of several genes involved in daily (circadian) rhythms, such as the sleep-wake cycle. Studies suggest that the duplication leads to an increase in the amount of RAI1 protein that is produced, which disrupts the expression of genes that influence circadian rhythms. These changes likely account for the sleep disturbances that occur with Potocki-Lupski syndrome. Too much RAI1 protein may also disrupt brain development and contribute to the neurological and behavioral features of this condition. It is unclear exactly how an extra copy of the RAI1 gene causes all of the features of this condition. Extra copies of other genes in the duplicated region likely also contribute to the specific signs and symptoms.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

The inheritance pattern of Potocki-Lupski syndrome is considered to be autosomal dominant , which means one copy of the 17p11.2 duplication in each cell is sufficient to cause the disorder.

However, most cases of Potocki-Lupski syndrome result from a new (de novo) chromosomal duplication that occurs as a random event during the formation of reproductive cells (eggs and sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their families. Less commonly, an affected person inherits the duplication from a parent.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Lupski syndrome affects an estimated 1 in 25,000 newborns worldwide. More than 1,000 cases have been described in the medical 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.

Abnormality of chromosome segregation · Very frequent (99-80%)

An abnormality of chromosome segregation.

Abnormality of the pharynx · Very frequent (99-80%)

An anomaly of the pharynx, i.e., of the tubular structure extending from the base of the skull superiorly to the esophageal inlet inferiorly.

Aphasia · Very frequent (99-80%)

An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.

Attention deficit hyperactivity disorder · Very frequent (99-80%)

Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient.

Autism · Very frequent (99-80%)

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV).

Dysarthria · Very frequent (99-80%)

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

Echolalia · Very frequent (99-80%)

Echolalia is the automatic imitative repetition of sounds, words, or phrases in the absence of explicit awareness. The repeated words or phrases are typically odd or used in a non-social manner. These can be words or phrases that the affected individual has heard or invented.

Expressive language delay · Very frequent (99-80%)

A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.

Other findings in the same source

From: Orphanet

Additional reported features include Failure to thrive (Very frequent (99-80%)); Global developmental delay (Very frequent (99-80%)); Hypotonia (Very frequent (99-80%)); Intellectual disability, mild (Very frequent (99-80%)); Sleep apnea (Very frequent (99-80%)); Abnormal cardiovascular system morphology (Frequent (79-30%)); Anxiety (Frequent (79-30%)); Broad forehead (Frequent (79-30%)); Downslanted palpebral fissures (Frequent (79-30%)); EEG abnormality (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Potocki-Lupski 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 Potocki-Lupski 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.