Potocki-Shaffer syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Shaffer syndrome is a disorder that affects the development of the bones, brain, and other tissues. The signs and symptoms of Potocki-Shaffer syndrome vary widely among affected individuals.

People with Potocki-Shaffer syndrome have enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. Openings in the parietal bones are normal during fetal development, but they usually close before birth. In people with this condition, the parietal foramina are larger than normal and may remain open after birth. Affected individuals often have a wide, short skull (brachycephaly). Their head size may be normal or unusually small.

Most people with Potocki-Shaffer syndrome have multiple noncancerous (benign) bone tumors called osteochondromas. In rare instances, these tumors become cancerous.

Other features of Potocki-Shaffer syndrome include intellectual disabilities, recurrent seizures (epilepsy), and delayed development of speech and motor skills (such as sitting and walking).

Many people with Potocki-Shaffer syndrome have distinctive facial features, such as a broad and tall forehead, a prominent bridge of the nose, a narrow distance between the nose and upper lip (a short philtrum), a short nose with a wide tip, and a downturned mouth.

Less commonly, Potocki-Shaffer syndrome causes vision problems; additional skeletal abnormalities; and defects in the heart, kidneys, and urinary tract.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Shaffer syndrome is caused by a deletion of genetic material from the short (p) arm of chromosome 11 at a position designated 11p11.2. Because of this change, Potocki-Shaffer syndrome is also known as proximal 11p deletion syndrome. The term "proximal" means that the missing piece is near the center of the chromosome. The size of the deletion varies among affected individuals. Studies suggest that an individual would need a deletion of at least 2.1 million DNA building blocks (base pairs), also written as 2.1 megabases (Mb), to develop all of the features associated with the condition. The loss of multiple genes within the deleted region causes the signs and symptoms of Potocki-Shaffer syndrome.

In particular, the deletion of the ALX4, PHF21A, and EXT2 genes is associated with several of the characteristic features of Potocki-Shaffer syndrome. The ALX4 and PHF21A proteins are involved in regulating the activity of genes, particularly those that play a role in the development of the brain, skull, and face. The EXT2 gene provides instructions for making a protein that modifies another protein that helps control the formation and growth of bones.

The deletion of the ALX4 gene causes the enlarged parietal foramina found in people with this condition. In addition, the loss of the PHF21A gene is the cause of intellectual disabilities and distinctive facial features in affected individuals. The deletion of the EXT2 gene is associated with the development of multiple osteochondromas. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Shaffer syndrome follows an autosomal dominant inheritance pattern, which means a deletion of genetic material from one copy of chromosome 11 is sufficient to cause the disorder. In some cases, an affected person inherits the chromosome with a deleted segment from an affected parent. More commonly, the condition results from a deletion that occurs during the formation of reproductive cells (eggs and sperm) in a parent or during early fetal development. In these instances, affected people typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Potocki-Shaffer syndrome is a rare condition, although its exact prevalence is unknown. Fewer than 100 cases have been reported in the scientific 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.

Brachycephaly · Very frequent (99-80%)

An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.

Broad nasal tip · Very frequent (99-80%)

Increase in width of the nasal tip.

Decreased skull ossification · Very frequent (99-80%)

A reduction in the magnitude or amount of ossification of the skull.

Depressed nasal tip · Very frequent (99-80%)

Decreased distance from the nasal tip to the nasal base.

Epicanthus · Very frequent (99-80%)

A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus.

Exostoses · Very frequent (99-80%)

An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage.

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.

Micrognathia · Very frequent (99-80%)

Developmental hypoplasia of the mandible.

Other findings in the same source

From: Orphanet

Additional reported features include Prominent nasal bridge (Very frequent (99-80%)); Underdeveloped nasal alae (Very frequent (99-80%)); Downturned corners of mouth (Frequent (79-30%)); Micropenis (Frequent (79-30%)); Nystagmus (Frequent (79-30%)); Parietal foramina (Frequent (79-30%)); Seizure (Frequent (79-30%)); Short philtrum (Frequent (79-30%)); Strabismus (Frequent (79-30%)); Anemia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Potocki-Shaffer 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-Shaffer 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.